Blast disease,caused by the hemibiotrophic ascomycete fungus,Magnaporthe oryzae,is a significant threat to sustainable rice production worldwide.Studies have shown that the blast fungus secretes vast arrays of functio...Blast disease,caused by the hemibiotrophic ascomycete fungus,Magnaporthe oryzae,is a significant threat to sustainable rice production worldwide.Studies have shown that the blast fungus secretes vast arrays of functionally diverse proteins into the host cell for a successful disease progression.However,the final destinations of these effector proteins inside the host cell and their role in advancing fungal pathogenesis remain a mystery.Here,we reported that a putative mitochondrial targeting non-classically secreted protein(MoMtp)positively regulates conidiogenesis and appressorium maturation in M.oryzae.Moreover,MoM TP gene deletion mutant strains triggered a hypersensitive response when inoculated on rice leaves displaying that MoMtp is essential for the virulence of M.oryzae.In addition,cell wall and oxidative stress results indicated that MoMtp is likely involved in the maintenance of the structural integrity of the fungus cell.Our study also demonstrates an upregulation in the expression pattern of the MoMTP gene at all stages of infection,indicating its possible regulatory role in host invasion and the infectious development of M.oryzae.Furthermore,Agrobacterium infiltration and sheath inoculation confirmed that MoMtpGFP protein is predominantly localized in the host mitochondria of tobacco leaf and rice cells.Taken together,we conclude that MoMtp protein likely promotes the normal conidiation and pathogenesis of M.oryzae and might have a role in disturbing the proper functioning of the host mitochondria during pathogen invasion.展开更多
Fusarium graminearum is an important plant pathogenic fungus that causes disease and yield reduction in many cereal crops, such as wheat and barley. Gyp8 stimulates GTP hydrolysis on Ypt1 in yeast. However, the functi...Fusarium graminearum is an important plant pathogenic fungus that causes disease and yield reduction in many cereal crops, such as wheat and barley. Gyp8 stimulates GTP hydrolysis on Ypt1 in yeast. However, the functions of Gyp8 in plant pathogenic fungi are still unknown. In this study, we investigated the roles of Fg Gyp8 in F. graminearum by genetic and pathological analyses. Through gene knockout and phenotypic analyses, we found that Fg Gyp8 is required for vegetative growth in F. graminearum. The conidiation, conidial size and number of septa per conidium of ΔFggyp8 mutant are significantly reduced when compared to the wild type PH-1. Furthermore, Fg Gyp8 is crucial for pathogenicity on wheat coleoptiles and wheat heads. Fg Gyp8 contains a conserved TBC domain. Domain deletion analysis showed that the TBC domain, C-and N-terminal regions of Fg Gyp8 are all important for its biological functions in F. graminearum. Moreover, we showed that Fg Gyp8 catalyzes the hydrolysis of the GTP on Fg Rab1 to GDP in vitro, indicating that Fg Gyp8 is a GTPase-activating protein(GAP) for Fg Rab1. In addition, we demonstrated that Fg Gyp8 is required for Fg Snc1-mediated fusion of secretory vesicles with the plasma membrane in F. graminearum. Finally, we showed that Fg Gyp8 has functional redundancy with another Fg Rab1 GAP, Fg Gyp1, in F. graminearum. Taken together, we conclude that Fg Gyp8 is required for vegetative growth, conidiogenesis, pathogenicity and acts as a GAP for Fg Rab1 in F. graminearum.展开更多
Burkholderia pseudomallei is the pathogen that causes melioidosis.Melioidosis has a long duration of chronic infection,atypical clinical manifestations at acute onset,and is prone to life-threatening complications and...Burkholderia pseudomallei is the pathogen that causes melioidosis.Melioidosis has a long duration of chronic infection,atypical clinical manifestations at acute onset,and is prone to life-threatening complications and poor prognosis.Understanding the pathogenesis and drug resistance mechanism of Burkholderia pseudomallei will effectively help the diagnosis and treatment of the disease and improve the prognosis.This review focuses on the extracellular movement of Burkholderia pseudomallei in host cells,the way of infecting host cells,virulence factors,and drug resistance mechanisms(efflux pumps,changes in target sites,etc.).This study provides a possible direction for the early diagnosis,treatment and control of melioidosis caused by this bacterium.展开更多
Hepatitis D virus(HDV) is a defective RNA virus which requires the help of hepatitis B virus(HBV) virus for its replication and assembly of new virions. HDV genome contains only one actively transcribed open reading f...Hepatitis D virus(HDV) is a defective RNA virus which requires the help of hepatitis B virus(HBV) virus for its replication and assembly of new virions. HDV genome contains only one actively transcribed open reading frame which encodes for two isoforms of hepatitis delta antigen. Post-translational modifications of small and large delta antigens(S-HDAg and L-HDAg) involving phosphorylation and isoprenylation respectively con- fer these antigens their specific properties. S-HDAg is required for the initiation of the viral genome replica- tion, whereas L-HDAg serves as a principal inhibitor of replication and is essential for the assembly of new virion particles. Immune mediation has usually been implicated in HDV-associated liver damage. The patho- genesis of HDV mainly involves interferon-α signaling inhibition, HDV-specific T-lymphocyte activation and cytokine responses, and tumor necrosis factor-alpha and nuclear factor kappa B signaling. Due to limited protein coding capacity, HDV makes use of host cel- lular proteins to accomplish their life cycle processes, including transcription, replication, post-transcriptional and translational modifications. This intimate host- pathogen interaction significantly alters cell proteome and is associated with an augmented expression of pro-inflammatory, growth and anti-apoptotic factorswhich explains severe necroinflammation and increased cell survival and an early progression to hepatocellular carcinoma in HDV patients. The understanding of the process of viral replication, HBV-HDV interactions, and etio-pathogenesis of the severe course of HDV infection is helpful in identifying the potential therapeutic targets in the virus life cycle for the prophylaxis and treatment of HDV infection and complications.展开更多
Wheat crown rot caused by Fusarium spp. is a common disease worldwide. Both Fusarium pseudograminearum and Fusarium graminearum infect wheat crown and produce mycotoxin leading to grain loss due to white head. F. pseu...Wheat crown rot caused by Fusarium spp. is a common disease worldwide. Both Fusarium pseudograminearum and Fusarium graminearum infect wheat crown and produce mycotoxin leading to grain loss due to white head. F. pseudograminearum （Fp） was reported in wheat from Henan Province of China a couple of years ago. The wheat crown rot （CR） caused by this new pathogen is as an emerging severe disease of wheat, which has recently expanded to several provinces in China and is, therefore, under rapid investigation. Colonization of wheat tissue by Fp is accomplished though the formation of a septated foot-shaped appressoria and generation of a penetration peg to break through the internal cells of leaf sheath. The molecular mechanism by which Fp regulates the pathogenesis on wheat host is unclear. Here, we report FpPDE1, a P-type ATPase-encoding predicted PDE1 orthologue gene of Magnaporthe oryzae, belonging to the DRS2 subfamily of aminophospholipid translocases. The gene deletion of FpPDE1 with the split-marker approach did not obviously affect hyphae growth and conidiation, but led to an attenuated virulence on wheat base stem and root. Our finding indicates that the putative aminophospholipid translocases is not essential for the infectious hyphae development in Fp.展开更多
Mucosal-associated invariant T(MAIT)cells have been described in liver and nonliver diseases,and they have been ascribed antimicrobial,immune regulatory,protective,and pathogenic roles.The goals of this review are to ...Mucosal-associated invariant T(MAIT)cells have been described in liver and nonliver diseases,and they have been ascribed antimicrobial,immune regulatory,protective,and pathogenic roles.The goals of this review are to describe their biological properties,indicate their involvement in chronic liver disease,and encourage investigations that clarify their actions and therapeutic implications.English abstracts were identified in PubMed by multiple search terms,and bibliographies were developed.MAIT cells are activated by restricted non-peptides of limited diversity and by multiple inflammatory cytokines.Diverse pro-inflammatory,anti-inflammatory,and immune regulatory cytokines are released;infected cells are eliminated;and memory cells emerge.Circulating MAIT cells are hyper-activated,immune exhausted,dysfunctional,and depleted in chronic liver disease.This phenotype lacks disease-specificity,and it does not predict the biological effects.MAIT cells have presumed protective actions in chronic viral hepatitis,alcoholic hepatitis,non-alcoholic fatty liver disease,primary sclerosing cholangitis,and decompensated cirrhosis.They have pathogenic and pro-fibrotic actions in autoimmune hepatitis and mixed actions in primary biliary cholangitis.Local factors in the hepatic microenvironment(cytokines,bile acids,gut-derived bacterial antigens,and metabolic by-products)may modulate their response in individual diseases.Investigational manipulations of function are warranted to establish an association with disease severity and outcome.In conclusion,MAIT cells constitute a disease-nonspecific,immune response to chronic liver inflammation and infection.Their pathological role has been deduced from their deficiencies during active liver disease,and future investigations must clarify this role,link it to outcome,and explore therapeutic interventions.展开更多
Objective To investigate the pathogenesis and immunogenicity of H9N2 influenza virus A/Guangzhou/333/99 （a reassortant of G1 and G9 viruses isolated from a female patient in 1999） in a mouse model of infection.Metho...Objective To investigate the pathogenesis and immunogenicity of H9N2 influenza virus A/Guangzhou/333/99 （a reassortant of G1 and G9 viruses isolated from a female patient in 1999） in a mouse model of infection.Methods Mice were infected with increasing virus titers.Viral load in the lungs and trachea was determined by EID50 assay.Pulmonary histopathology was assessed by hematoxylin‐eosin staining.Anti‐HI antibody titers and T‐cell responses to viral HA were determined by ELISPOT and confirmed by flow cytometry.Results Mice presented a mild syndrome after intranasal infection with A/Guangzhou/333/99 （H9N2） influenza virus.Virus was detected in the trachea and lungs of mice harvested on days 3,6,and 9 post‐infection.A T‐cell response to viral HA was detected on day 6 and H9 HA‐specific CD 4＋ T‐cells predominated.Seroconversion was detected after 14 days and antibody persisted for at least 28 weeks.Conclusion Our results suggest that H9N2 （A/Guangzhou/333/99） can replicate in the murine respiratory tract without prior adaptation,and both humoral and cell‐mediated immunity play an important role in the immune response.展开更多
Porcine reproductive and respiratory syndrome virus (PRRSV) has been recognized as one of the most important pathogens of pigs throughout the world. In 2006, more than 10 provinces of China have experienced an epizoot...Porcine reproductive and respiratory syndrome virus (PRRSV) has been recognized as one of the most important pathogens of pigs throughout the world. In 2006, more than 10 provinces of China have experienced an epizootic outbreak of pig diseases characterized by high fever, reddened skin and high morbidity and mortality. From June 2006 to April 2007, we have investigated some clinical samples in Hubei province by RT-PCR and cloned several major genes, N, GP5 and NSP2 gene, shown in this study. Phylogenetic analysis of these genes revealed that the highly pathogenic PRRSV variant, ZB, was responsible for 2006 emergent outbreak of pig disease in Hubei province similar with those variants isolated from other provinces in China in 2006, and belongs to the NA-type PRRSV. In the PRRSV variants, the N and GP5 shear about 90% identity with prototypic ATCC VR-2332 and some typical NA-type Chinese isolates, except the 2850bp NSP2 gene (only shares 65% identity with ATCC VR-2332). But they all shear more than and 97% identity with other highly pathogenetic Chinese PRRSV strains. Additionally, there are extensive amino acid (aa) mutations in the GP5 protein and 2 deletions in the Nsp2 protein when compared with the previous isolates. Most of the variants found in 2006 epizootic outbreak of pig diseases in China were the farthest variants from the typical NA-type PRRSV in phylogenetic distance, and these diversities may be responsible for the differences in the pathogenicity observed between these variants and original Chinese PRRSV strains.展开更多
Based on the characteristics of the epidemic situation and the authors’understanding of the related ancient books and documents,this paper explores the etiology and pathogenesis of Corona Virus Disease 2019(COVID-19)...Based on the characteristics of the epidemic situation and the authors’understanding of the related ancient books and documents,this paper explores the etiology and pathogenesis of Corona Virus Disease 2019(COVID-19)from 5 aspects:abnormal climate in"warm winter",unique geographical location,pathogenesis evolution of cold and dampness mixed with insidious dryness,transmission and change of"triple energizer"of toxic pathogens,and game between healthy Qi and toxic pathogens.Combined with the special treatment of traditional Chinese medicine(TCM),the purpose is to make a modest contribution to curbing the epidemic situation with TCM.展开更多
Reliable knowledge on pathogenic agents contributes to effective plant protection.For most plant pathogens,maintaining protein homeostasis(proteostasis)is essential for unfolding the cellular functions to survive and ...Reliable knowledge on pathogenic agents contributes to effective plant protection.For most plant pathogens,maintaining protein homeostasis(proteostasis)is essential for unfolding the cellular functions to survive and thrive.However,the fungal proteins involved in proteostasis remain poorly characterized in the process of pathogenesis.In this study,we characterized the function of the nascent polypeptideassociated complex(NAC)in Fusarium graminearum(F.graminearum)(FgNAC),one of the top 10 fungal pathogens with predominant scientific/economic importance.We found that FgNACa,a subunit of FgNAC,manifests high structural and functional similarity to its homologous counterparts in yeast and other species.The mutants of F.graminearum lacking NACa are viable but suffer significant defects in vegetative growth,conidial production,and pathogenesis.In addition,we show here that FgNACa can interact with another subunit of NAC(FgNACb)in a yeast-two-hybrid assay.The subcellular localization results show that FgNACa and FgNACb are predominantly localized in the cytoplasm.Future studies should focus on deciphering the mechanism by which NAC orchestrates protein biogenesis and consequentially modulates development and pathogenesis.展开更多
[Objectives]The paper was to understand the species and pathogenicity of the pathogen causing potato early blight in winter.[Methods]The occurrence of potato early blight was investigated in 5 winter potato growing ar...[Objectives]The paper was to understand the species and pathogenicity of the pathogen causing potato early blight in winter.[Methods]The occurrence of potato early blight was investigated in 5 winter potato growing areas in Yunnan Province.The disease samples were collected from two locations(Zhutang Village and Zhanai Village,Pu'er City)where the occurrence of early blight was severe.The pathogen was isolated and purified in laboratory and identified by morphological characteristics and phylogenetic analysis of ITS gene sequence.And it was further verified via re-inoculation by Koch's rules.The growth characteristics and pathogenicity of isolates in different seasons were analyzed with 4 strains of Alternaria isolated in spring(EYZ,EYAX,TA1 and TAC)as controls.[Results]Early blight occurred in varying degrees in the 5 winter potato growing areas,and the incidence of early blight was up to 100%in some plots in Lancang County,Pu'er City.A total of 35 strains of Alternaria were isolated from plots with high incidence,which were divided into two types according to colony morphology.The first type was round colonies with smooth edges and gray white fronts,and the second type was round colonies with rough edges and gray black fronts.Three strains LC1,LC2,LC3 of the first type and two strains ZT3 and ZT8 of the second type were selected and identified as Alternaria alternata through morphological and molecular identification.Re-inoculation test further confirmed that the pathogen was A.alternata.Meantime,it was found that the growth rate of colonies isolated in winter was relatively slow,and there was no significant difference between the pathogenicity of LC1 and TA1,but the pathogenicity of strains isolated in winter was generally higher than that isolated in spring.[Conclusions]It is confirmed that the pathogen causing potato early blight in winter is A.alternata in Yunnan Province.The results will lay a foundation for the research of pathogenesis,occurrence regularity and disease control of A.alternata in winter potato.展开更多
The pathogenesis-related proteins 1 (PR-1) gene family play important roles in the plant metabolism in response to biotic and abiotic stresses. The wheat TdPR1.2 has been previously isolated and characterized. Here we...The pathogenesis-related proteins 1 (PR-1) gene family play important roles in the plant metabolism in response to biotic and abiotic stresses. The wheat TdPR1.2 has been previously isolated and characterized. Here we showed by bio-informatic analysis that TdPR1.2 contains six cysteine residues that are conserved between all PR-1 proteins tested. Using ScanProsite tool, we found that TdPR1.2 structure has a CRISP family signature 1 and 2 located at the C-terminal part of the protein. Those two domains are conserved in many identified PR1.2 proteins in plants. Moreover, SignalIP-5.0 analysis revealed that TdPR1.2 contains a putative signal peptide formed by 25 amino acids at the N-terminal extremity. The presence of this signal peptide suggested that the mature proteins will be secreted after the cleavage of the signal sequence. Further, we investigate the role of the TdPR1.2 proteins in the growth of <i>Escherichia coli</i> transformants cells under different abiotic stresses. Our results showed that the full-length form of TdPR1.2 enhanced tolerance of <i>E. coli</i> against salt and osmotic stress but not to KCl. Moreover, TdPR1.2 protein confers bacterial tolerance to heavy metals in solid and liquid mediums. Based on these results, we suggest that the TdPR1.2 protein could play an important role in response to abiotic stress conditions.展开更多
Upper airway cough syndrome refers to a clinical syndrome with chronic cough as the main manifestation caused by the reverse flow of secretions from various upper airway diseases such as allergic rhinitis,rhino-sinusi...Upper airway cough syndrome refers to a clinical syndrome with chronic cough as the main manifestation caused by the reverse flow of secretions from various upper airway diseases such as allergic rhinitis,rhino-sinusitis,adenoid hypertrophy and other parts of the nose and pharynx.Professor Yin Dan believes that the main disease of upper airway cough syndrome is due to cold fluid retained in lung,blood stasis endogenous,compound feeling of wind evil.The pathogenesis is external wind evil and the hidden pathogen together to cause the disease.In the treatment,the warm cold fluid retention is the core,accompanied by the activation of blood and wind,so that the wind evil can go away,the cold evil can be warmed,the phlegm can be removed,and the blood stasis can be dispersed,so as to achieve the purpose of treating the upper airway cough syndrome of the children’s cold fluid retention in lung.展开更多
Myocarditis is an inflammatory cardiac disease characterized by the destruction of myocardial cells, infiltration of interstitial inflammatory cells, and fibrosis, and is becoming a major public health concern. The ae...Myocarditis is an inflammatory cardiac disease characterized by the destruction of myocardial cells, infiltration of interstitial inflammatory cells, and fibrosis, and is becoming a major public health concern. The aetiology of myocarditis continues to broaden as new pathogens and drugs emerge. The relationship between immune checkpoint inhibitors, severe acute respiratory syndrome coronavirus 2, vaccines against coronavirus disease-2019, and myocarditis has attracted increased attention. Immunopathological processes play an important role in the different phases of myocarditis, affecting disease occurrence, development, and prognosis. Excessive immune activation can induce severe myocardial injury and lead to fulminant myocarditis,whereas chronic inflammation can lead to cardiac remodelling and inflammatory dilated cardiomyopathy. The use of immunosuppressive treatments, particularly cytotoxic agents, for myocarditis, remains controversial. While reasonable and effective immunomodulatory therapy is the general trend. This review focuses on the current understanding of the aetiology and immunopathogenesis of myocarditis and offers new perspectives on immunomodulatory therapies.展开更多
Constructed wetlands(CwW)are well known nature-based systems for water treatment.This study evaluated the efficiency and effectiveness of seven domestic wastewater treatment systems based on horizontal flow CWs in Jar...Constructed wetlands(CwW)are well known nature-based systems for water treatment.This study evaluated the efficiency and effectiveness of seven domestic wastewater treatment systems based on horizontal flow CWs in Jarabacoa,the Dominican Republic.The results showed that the CWs were efficient in reducing the degree of contamination of wastewater to levels below the Dominican wastewater discharge standards for parameters such as the 5-day biochemical oxygen demand(BOD5)and chemical oxygen demand,but not for the removal of phosphorus and fecal coliforms.In addition,a horizontal flow subsurface wetland in the peri-urban area El Dorado was evaluated in terms of the performance of wastewater treatment in tropical climatic conditions.The concentrations of heavy metals,such as zinc,copper,chromium,and iron,were found to decrease in the effluent of the wetland,and the concentrations for nickel and manganese tended to increase.The levels of heavy metals in the effluent were lower than the limit values of the Dominican wastewater discharge standards.The construction cost of these facilities was around 200 USD per population equivalent,similar to the cost in other countries in the same region.This study suggested some solutions to the improved performance of CWs:selection of a microbial flora that guarantees the reduction of nitrates and nitrites to molecular nitrogen,use of endemic plants that bioaccumulate heavy metals,combination of constructed wetlands with filtration on activated carbon,and inclusion of water purification processes that allow to evaluate the reuse of treated water.展开更多
The stamping-out strategy has been used to control highly pathogenic avian influenza viruses in many countries,driven by the belief that vaccination would not be successful against such viruses and fears that avian in...The stamping-out strategy has been used to control highly pathogenic avian influenza viruses in many countries,driven by the belief that vaccination would not be successful against such viruses and fears that avian influenza virus in vaccinated birds would evolve more rapidly and pose a greater risk to humans.In this review,we summarize the successes in controlling highly pathogenic avian influenza in China and make suggestions regarding the requirements for vaccine selection and effectiveness.In addition,we present evidence that vaccination of poultry not only eliminates human infection with avian influenza virus,but also significantly reduces and abolishes some harmful characteristics of avian influenza virus.展开更多
Bordetella bronchiseptica(Bb)is recognized as a leading cause of respiratory diseases in dogs and cats.However,epidemiological data on Bb in dogs and cats in China are still limited,and there is no commercially availa...Bordetella bronchiseptica(Bb)is recognized as a leading cause of respiratory diseases in dogs and cats.However,epidemiological data on Bb in dogs and cats in China are still limited,and there is no commercially available vaccine.Live vaccines containing Bb that are widely used abroad are generally efective but can establish latency and potentially reactivate to cause illness in some immunodefcient vaccinated recipients,raising safety concerns.In this study,34 canine-derived and two feline-derived Bb strains were isolated from 1809 canine and 113 feline nasopharyngeal swab samples collected from eight provinces in China from 2021 to 2023.The PCR results showed that the percentage of positive Bb was 22.94%(441/1922),and more than 90%of the Bb isolates had four virulence factor-encoding genes(VFGs),namely,fhaB,prn,betA and dnt.All the isolated strains displayed a multidrug-resistant phenotype.The virulence of 10 Bb strains isolated from dogs with respiratory symptoms was tested in mice,and we found that eight isolates were highly virulent.Furthermore,the eight Bb isolates with high virulence were inactivated and intramuscularly injected into mice,and three Bb strains(WH1218,WH1203 and WH1224)with the best protective efcacy were selected.Dogs immunized with these three strains exhibited strong protection against challenge with the Bb feld strain WH1218.Ultimately,the WH1218 strain with the greatest protection in dogs was selected as the vaccine candidate.Dogs and cats that received a vaccine containing 109 CFU of the inactivated WH1218 strain showed complete protection against challenge with the Bb feld strain WH1218.This study revealed that Bb is an important pathogen that causes respiratory diseases in domestic dogs and cats in China,and all the isolates exhibited multidrug resistance.The present work contributes to the current understanding of the prevalence,antimicrobial resistance,and virulence genes of Bb in domestic dogs and cats.Additionally,our results suggest that the WH1218 strain is a promising candidate safe and efcacious inactivated Bb vaccine.展开更多
Pathogenic microorganisms produce numerous metabolites,including volatile organic compounds(VOCs).Monitoring these metabolites in biological matrices(e.g.,urine,blood,or breath)can reveal the presence of specific micr...Pathogenic microorganisms produce numerous metabolites,including volatile organic compounds(VOCs).Monitoring these metabolites in biological matrices(e.g.,urine,blood,or breath)can reveal the presence of specific microorganisms,enabling the early diagnosis of infections and the timely implementation of tar-geted therapy.However,complex matrices only contain trace levels of VOCs,and their constituent com-ponents can hinder determination of these compounds.Therefore,modern analytical techniques enabling the non-invasive identification and precise quantification of microbial VOCs are needed.In this paper,we discuss bacterial VOC analysis under in vitro conditions,in animal models and disease diagnosis in humans,including techniques for offline and online analysis in clinical settings.We also consider the advantages and limitations of novel microextraction techniques used to prepare biological samples for VOC analysis,in addition to reviewing current clinical studies on bacterial volatilomes that address inter-species in-teractions,the kinetics of VOC metabolism,and species-and drug-resistance specificity.展开更多
Avian pathogenic Escherichia coli(APEC)belonging to extraintestinal pathogenic E.coli(ExPEC)can cause severe infections in extraintestinal tissues in birds and humans,such as the lungs and blood.MprA(microcin producti...Avian pathogenic Escherichia coli(APEC)belonging to extraintestinal pathogenic E.coli(ExPEC)can cause severe infections in extraintestinal tissues in birds and humans,such as the lungs and blood.MprA(microcin production regulation,locus A,herein renamed AbsR,a blood survival regulator),a member of the MarR(multiple antibiotic resistance regulator)transcriptional regulator family,governs the expression of capsule biosynthetic genes in human ExPEC and represents a promising druggable target for antimicrobials.However,a deep understanding of the AbsR regulatory mechanism as well as its regulon is lacking.In this study,we present a systems-level analysis of the APEC AbsR regulon using ChIP-Seq(chromatin immunoprecipitation sequencing)and RNA-Seq(RNA sequencing)methods.We found that AbsR directly regulates 99 genes and indirectly regulates 667 genes.Furthermore,we showed that:1)AbsR contributes to antiphagocytotic effects by macrophages and virulence in a mouse model for systemic infection by directly activating the capsular gene cluster;2)AbsR positively impacts biofilm formation via direct regulation of the T2SS(type II secretion system)but plays a marginal role in virulence;and 3)AbsR directly upregulates the acid tolerance signaling system EvgAS to withstand acid stress but is dispensable in ExPEC virulence.Finally,our data indicate that the role of AbsR in virulence gene regulation is relatively conserved in ExPEC strains.Altogether,this study provides a comprehensive analysis of the AbsR regulon and regulatory mechanism,and our data suggest that AbsR likely influences virulence primarily through the control of capsule production.Interestingly,we found that AbsR severely represses the expression of the type I-F CRISPR(clustered regularly interspaced short palindromic repeats)-Cas(CRISPR associated)systems,which could have implications in CRISPR biology and application.展开更多
The necrotrophic fungus, Sclerotinia sclerotiorum, employs an array of cell wall-degrading enzymes(CWDEs), including cellulase, to dismantle host cell walls. However, the molecular mechanisms through which S. scleroti...The necrotrophic fungus, Sclerotinia sclerotiorum, employs an array of cell wall-degrading enzymes(CWDEs), including cellulase, to dismantle host cell walls. However, the molecular mechanisms through which S. sclerotiorum degrades cellulose remain elusive. Here, we unveil a novel secretory cellobiohydrolase, SsdchA, characterized by a signal peptide and a Glyco_hydro_7(GH7) domain. SsdchA exhibits a robust expression of during early infection stages. Interestingly, colony morphology and growth rates remain unaffected across the wild-type, SsdchA deletion strains and SsdchA overexpression strains on potato dextrose agar(PDA) medium. Nevertheless, the pathogenicity and cellobiohydrolase activity decreased in the SsdchA deletion strains, but enhanced in the SsdchA overexpression strains. Moreover,the heterologous expression of SsdchA in Arabidopsis thaliana leads to reduced cellulose content and heightened susceptibility to S. sclerotiorum. Collectively, our data underscore the pivotal role of the novel cellobiohydrolase SsdchA in the pathogenicity of S. sclerotiorum.展开更多
基金funded by the National Natural Science Foundation of China(32172364 to Shihong Zhang and 32272513 to Zonghua Wang)Fujian Agriculture and Forestry University scholarship,China for Wajjiha Batool。
文摘Blast disease,caused by the hemibiotrophic ascomycete fungus,Magnaporthe oryzae,is a significant threat to sustainable rice production worldwide.Studies have shown that the blast fungus secretes vast arrays of functionally diverse proteins into the host cell for a successful disease progression.However,the final destinations of these effector proteins inside the host cell and their role in advancing fungal pathogenesis remain a mystery.Here,we reported that a putative mitochondrial targeting non-classically secreted protein(MoMtp)positively regulates conidiogenesis and appressorium maturation in M.oryzae.Moreover,MoM TP gene deletion mutant strains triggered a hypersensitive response when inoculated on rice leaves displaying that MoMtp is essential for the virulence of M.oryzae.In addition,cell wall and oxidative stress results indicated that MoMtp is likely involved in the maintenance of the structural integrity of the fungus cell.Our study also demonstrates an upregulation in the expression pattern of the MoMTP gene at all stages of infection,indicating its possible regulatory role in host invasion and the infectious development of M.oryzae.Furthermore,Agrobacterium infiltration and sheath inoculation confirmed that MoMtpGFP protein is predominantly localized in the host mitochondria of tobacco leaf and rice cells.Taken together,we conclude that MoMtp protein likely promotes the normal conidiation and pathogenesis of M.oryzae and might have a role in disturbing the proper functioning of the host mitochondria during pathogen invasion.
基金National Natural Science Foundation of China (31970141)the Natural Science Foundation of Fujian Province, China (2020J06047)+1 种基金the Foundation of Minjiang University, China (MJY19019)the Foundation of Fujian Agriculture and Forestry University, China (KFb22050XA)。
文摘Fusarium graminearum is an important plant pathogenic fungus that causes disease and yield reduction in many cereal crops, such as wheat and barley. Gyp8 stimulates GTP hydrolysis on Ypt1 in yeast. However, the functions of Gyp8 in plant pathogenic fungi are still unknown. In this study, we investigated the roles of Fg Gyp8 in F. graminearum by genetic and pathological analyses. Through gene knockout and phenotypic analyses, we found that Fg Gyp8 is required for vegetative growth in F. graminearum. The conidiation, conidial size and number of septa per conidium of ΔFggyp8 mutant are significantly reduced when compared to the wild type PH-1. Furthermore, Fg Gyp8 is crucial for pathogenicity on wheat coleoptiles and wheat heads. Fg Gyp8 contains a conserved TBC domain. Domain deletion analysis showed that the TBC domain, C-and N-terminal regions of Fg Gyp8 are all important for its biological functions in F. graminearum. Moreover, we showed that Fg Gyp8 catalyzes the hydrolysis of the GTP on Fg Rab1 to GDP in vitro, indicating that Fg Gyp8 is a GTPase-activating protein(GAP) for Fg Rab1. In addition, we demonstrated that Fg Gyp8 is required for Fg Snc1-mediated fusion of secretory vesicles with the plasma membrane in F. graminearum. Finally, we showed that Fg Gyp8 has functional redundancy with another Fg Rab1 GAP, Fg Gyp1, in F. graminearum. Taken together, we conclude that Fg Gyp8 is required for vegetative growth, conidiogenesis, pathogenicity and acts as a GAP for Fg Rab1 in F. graminearum.
基金Supported by the National Natural Science Foundation of China(No.82260001)Key Special Project Supported by the National Key R&D Plan of the Ministry of Science and Technology(No.2022YFC2305004)。
文摘Burkholderia pseudomallei is the pathogen that causes melioidosis.Melioidosis has a long duration of chronic infection,atypical clinical manifestations at acute onset,and is prone to life-threatening complications and poor prognosis.Understanding the pathogenesis and drug resistance mechanism of Burkholderia pseudomallei will effectively help the diagnosis and treatment of the disease and improve the prognosis.This review focuses on the extracellular movement of Burkholderia pseudomallei in host cells,the way of infecting host cells,virulence factors,and drug resistance mechanisms(efflux pumps,changes in target sites,etc.).This study provides a possible direction for the early diagnosis,treatment and control of melioidosis caused by this bacterium.
文摘Hepatitis D virus(HDV) is a defective RNA virus which requires the help of hepatitis B virus(HBV) virus for its replication and assembly of new virions. HDV genome contains only one actively transcribed open reading frame which encodes for two isoforms of hepatitis delta antigen. Post-translational modifications of small and large delta antigens(S-HDAg and L-HDAg) involving phosphorylation and isoprenylation respectively con- fer these antigens their specific properties. S-HDAg is required for the initiation of the viral genome replica- tion, whereas L-HDAg serves as a principal inhibitor of replication and is essential for the assembly of new virion particles. Immune mediation has usually been implicated in HDV-associated liver damage. The patho- genesis of HDV mainly involves interferon-α signaling inhibition, HDV-specific T-lymphocyte activation and cytokine responses, and tumor necrosis factor-alpha and nuclear factor kappa B signaling. Due to limited protein coding capacity, HDV makes use of host cel- lular proteins to accomplish their life cycle processes, including transcription, replication, post-transcriptional and translational modifications. This intimate host- pathogen interaction significantly alters cell proteome and is associated with an augmented expression of pro-inflammatory, growth and anti-apoptotic factorswhich explains severe necroinflammation and increased cell survival and an early progression to hepatocellular carcinoma in HDV patients. The understanding of the process of viral replication, HBV-HDV interactions, and etio-pathogenesis of the severe course of HDV infection is helpful in identifying the potential therapeutic targets in the virus life cycle for the prophylaxis and treatment of HDV infection and complications.
基金financially supported by the National Special Fund for Agro-scientific Research in the Public Interest of China(201503112)the Basic and Advance Technology Research Program in Henan Province,China(152300410073)the Talent Project of Henan Agricultural University,China(3600861)
文摘Wheat crown rot caused by Fusarium spp. is a common disease worldwide. Both Fusarium pseudograminearum and Fusarium graminearum infect wheat crown and produce mycotoxin leading to grain loss due to white head. F. pseudograminearum （Fp） was reported in wheat from Henan Province of China a couple of years ago. The wheat crown rot （CR） caused by this new pathogen is as an emerging severe disease of wheat, which has recently expanded to several provinces in China and is, therefore, under rapid investigation. Colonization of wheat tissue by Fp is accomplished though the formation of a septated foot-shaped appressoria and generation of a penetration peg to break through the internal cells of leaf sheath. The molecular mechanism by which Fp regulates the pathogenesis on wheat host is unclear. Here, we report FpPDE1, a P-type ATPase-encoding predicted PDE1 orthologue gene of Magnaporthe oryzae, belonging to the DRS2 subfamily of aminophospholipid translocases. The gene deletion of FpPDE1 with the split-marker approach did not obviously affect hyphae growth and conidiation, but led to an attenuated virulence on wheat base stem and root. Our finding indicates that the putative aminophospholipid translocases is not essential for the infectious hyphae development in Fp.
文摘Mucosal-associated invariant T(MAIT)cells have been described in liver and nonliver diseases,and they have been ascribed antimicrobial,immune regulatory,protective,and pathogenic roles.The goals of this review are to describe their biological properties,indicate their involvement in chronic liver disease,and encourage investigations that clarify their actions and therapeutic implications.English abstracts were identified in PubMed by multiple search terms,and bibliographies were developed.MAIT cells are activated by restricted non-peptides of limited diversity and by multiple inflammatory cytokines.Diverse pro-inflammatory,anti-inflammatory,and immune regulatory cytokines are released;infected cells are eliminated;and memory cells emerge.Circulating MAIT cells are hyper-activated,immune exhausted,dysfunctional,and depleted in chronic liver disease.This phenotype lacks disease-specificity,and it does not predict the biological effects.MAIT cells have presumed protective actions in chronic viral hepatitis,alcoholic hepatitis,non-alcoholic fatty liver disease,primary sclerosing cholangitis,and decompensated cirrhosis.They have pathogenic and pro-fibrotic actions in autoimmune hepatitis and mixed actions in primary biliary cholangitis.Local factors in the hepatic microenvironment(cytokines,bile acids,gut-derived bacterial antigens,and metabolic by-products)may modulate their response in individual diseases.Investigational manipulations of function are warranted to establish an association with disease severity and outcome.In conclusion,MAIT cells constitute a disease-nonspecific,immune response to chronic liver inflammation and infection.Their pathological role has been deduced from their deficiencies during active liver disease,and future investigations must clarify this role,link it to outcome,and explore therapeutic interventions.
基金supported by the National Basic Research Program of China (973 program: 2005CB523006)
文摘Objective To investigate the pathogenesis and immunogenicity of H9N2 influenza virus A/Guangzhou/333/99 （a reassortant of G1 and G9 viruses isolated from a female patient in 1999） in a mouse model of infection.Methods Mice were infected with increasing virus titers.Viral load in the lungs and trachea was determined by EID50 assay.Pulmonary histopathology was assessed by hematoxylin‐eosin staining.Anti‐HI antibody titers and T‐cell responses to viral HA were determined by ELISPOT and confirmed by flow cytometry.Results Mice presented a mild syndrome after intranasal infection with A/Guangzhou/333/99 （H9N2） influenza virus.Virus was detected in the trachea and lungs of mice harvested on days 3,6,and 9 post‐infection.A T‐cell response to viral HA was detected on day 6 and H9 HA‐specific CD 4＋ T‐cells predominated.Seroconversion was detected after 14 days and antibody persisted for at least 28 weeks.Conclusion Our results suggest that H9N2 （A/Guangzhou/333/99） can replicate in the murine respiratory tract without prior adaptation,and both humoral and cell‐mediated immunity play an important role in the immune response.
基金supported in part by a National Key Technologies R&D Program (2006BAD06A01) National "973 Project" (2005CB523000, 2006CB- 933102) from the Ministry of Science and Technology, People’s Republic of China.
文摘Porcine reproductive and respiratory syndrome virus (PRRSV) has been recognized as one of the most important pathogens of pigs throughout the world. In 2006, more than 10 provinces of China have experienced an epizootic outbreak of pig diseases characterized by high fever, reddened skin and high morbidity and mortality. From June 2006 to April 2007, we have investigated some clinical samples in Hubei province by RT-PCR and cloned several major genes, N, GP5 and NSP2 gene, shown in this study. Phylogenetic analysis of these genes revealed that the highly pathogenic PRRSV variant, ZB, was responsible for 2006 emergent outbreak of pig disease in Hubei province similar with those variants isolated from other provinces in China in 2006, and belongs to the NA-type PRRSV. In the PRRSV variants, the N and GP5 shear about 90% identity with prototypic ATCC VR-2332 and some typical NA-type Chinese isolates, except the 2850bp NSP2 gene (only shares 65% identity with ATCC VR-2332). But they all shear more than and 97% identity with other highly pathogenetic Chinese PRRSV strains. Additionally, there are extensive amino acid (aa) mutations in the GP5 protein and 2 deletions in the Nsp2 protein when compared with the previous isolates. Most of the variants found in 2006 epizootic outbreak of pig diseases in China were the farthest variants from the typical NA-type PRRSV in phylogenetic distance, and these diversities may be responsible for the differences in the pathogenicity observed between these variants and original Chinese PRRSV strains.
基金the funding support from the National Natural Science Foundation of China(No.81774126)Hunan Provincial Innovation Foundation for Postgraduate(No.CX2018B481)Program for First-class Disciplines of Hunan Province in the Direction of Traditional Chinese and Western Medicine(No.2018ZXYJH20).
文摘Based on the characteristics of the epidemic situation and the authors’understanding of the related ancient books and documents,this paper explores the etiology and pathogenesis of Corona Virus Disease 2019(COVID-19)from 5 aspects:abnormal climate in"warm winter",unique geographical location,pathogenesis evolution of cold and dampness mixed with insidious dryness,transmission and change of"triple energizer"of toxic pathogens,and game between healthy Qi and toxic pathogens.Combined with the special treatment of traditional Chinese medicine(TCM),the purpose is to make a modest contribution to curbing the epidemic situation with TCM.
基金This work was supported by the National Natural Science Foundation of China(31471737,31671984,and 31801691)the Advanced Programs of Guizhou Province for the Returned Overseas Scholars([2018]02).
文摘Reliable knowledge on pathogenic agents contributes to effective plant protection.For most plant pathogens,maintaining protein homeostasis(proteostasis)is essential for unfolding the cellular functions to survive and thrive.However,the fungal proteins involved in proteostasis remain poorly characterized in the process of pathogenesis.In this study,we characterized the function of the nascent polypeptideassociated complex(NAC)in Fusarium graminearum(F.graminearum)(FgNAC),one of the top 10 fungal pathogens with predominant scientific/economic importance.We found that FgNACa,a subunit of FgNAC,manifests high structural and functional similarity to its homologous counterparts in yeast and other species.The mutants of F.graminearum lacking NACa are viable but suffer significant defects in vegetative growth,conidial production,and pathogenesis.In addition,we show here that FgNACa can interact with another subunit of NAC(FgNACb)in a yeast-two-hybrid assay.The subcellular localization results show that FgNACa and FgNACb are predominantly localized in the cytoplasm.Future studies should focus on deciphering the mechanism by which NAC orchestrates protein biogenesis and consequentially modulates development and pathogenesis.
基金Major Science and Technology Special Plan of Yunnan Department of Science and Technology(202102AE090018)Key Research and Development Program of Hainan Province(ZDYF2021XDNY291).
文摘[Objectives]The paper was to understand the species and pathogenicity of the pathogen causing potato early blight in winter.[Methods]The occurrence of potato early blight was investigated in 5 winter potato growing areas in Yunnan Province.The disease samples were collected from two locations(Zhutang Village and Zhanai Village,Pu'er City)where the occurrence of early blight was severe.The pathogen was isolated and purified in laboratory and identified by morphological characteristics and phylogenetic analysis of ITS gene sequence.And it was further verified via re-inoculation by Koch's rules.The growth characteristics and pathogenicity of isolates in different seasons were analyzed with 4 strains of Alternaria isolated in spring(EYZ,EYAX,TA1 and TAC)as controls.[Results]Early blight occurred in varying degrees in the 5 winter potato growing areas,and the incidence of early blight was up to 100%in some plots in Lancang County,Pu'er City.A total of 35 strains of Alternaria were isolated from plots with high incidence,which were divided into two types according to colony morphology.The first type was round colonies with smooth edges and gray white fronts,and the second type was round colonies with rough edges and gray black fronts.Three strains LC1,LC2,LC3 of the first type and two strains ZT3 and ZT8 of the second type were selected and identified as Alternaria alternata through morphological and molecular identification.Re-inoculation test further confirmed that the pathogen was A.alternata.Meantime,it was found that the growth rate of colonies isolated in winter was relatively slow,and there was no significant difference between the pathogenicity of LC1 and TA1,but the pathogenicity of strains isolated in winter was generally higher than that isolated in spring.[Conclusions]It is confirmed that the pathogen causing potato early blight in winter is A.alternata in Yunnan Province.The results will lay a foundation for the research of pathogenesis,occurrence regularity and disease control of A.alternata in winter potato.
文摘The pathogenesis-related proteins 1 (PR-1) gene family play important roles in the plant metabolism in response to biotic and abiotic stresses. The wheat TdPR1.2 has been previously isolated and characterized. Here we showed by bio-informatic analysis that TdPR1.2 contains six cysteine residues that are conserved between all PR-1 proteins tested. Using ScanProsite tool, we found that TdPR1.2 structure has a CRISP family signature 1 and 2 located at the C-terminal part of the protein. Those two domains are conserved in many identified PR1.2 proteins in plants. Moreover, SignalIP-5.0 analysis revealed that TdPR1.2 contains a putative signal peptide formed by 25 amino acids at the N-terminal extremity. The presence of this signal peptide suggested that the mature proteins will be secreted after the cleavage of the signal sequence. Further, we investigate the role of the TdPR1.2 proteins in the growth of <i>Escherichia coli</i> transformants cells under different abiotic stresses. Our results showed that the full-length form of TdPR1.2 enhanced tolerance of <i>E. coli</i> against salt and osmotic stress but not to KCl. Moreover, TdPR1.2 protein confers bacterial tolerance to heavy metals in solid and liquid mediums. Based on these results, we suggest that the TdPR1.2 protein could play an important role in response to abiotic stress conditions.
文摘Upper airway cough syndrome refers to a clinical syndrome with chronic cough as the main manifestation caused by the reverse flow of secretions from various upper airway diseases such as allergic rhinitis,rhino-sinusitis,adenoid hypertrophy and other parts of the nose and pharynx.Professor Yin Dan believes that the main disease of upper airway cough syndrome is due to cold fluid retained in lung,blood stasis endogenous,compound feeling of wind evil.The pathogenesis is external wind evil and the hidden pathogen together to cause the disease.In the treatment,the warm cold fluid retention is the core,accompanied by the activation of blood and wind,so that the wind evil can go away,the cold evil can be warmed,the phlegm can be removed,and the blood stasis can be dispersed,so as to achieve the purpose of treating the upper airway cough syndrome of the children’s cold fluid retention in lung.
基金supported by the National Natural Science Foundation of China (81790624 and C-0052)Natural Science Foundation of Hubei Province (2020CFA016)。
文摘Myocarditis is an inflammatory cardiac disease characterized by the destruction of myocardial cells, infiltration of interstitial inflammatory cells, and fibrosis, and is becoming a major public health concern. The aetiology of myocarditis continues to broaden as new pathogens and drugs emerge. The relationship between immune checkpoint inhibitors, severe acute respiratory syndrome coronavirus 2, vaccines against coronavirus disease-2019, and myocarditis has attracted increased attention. Immunopathological processes play an important role in the different phases of myocarditis, affecting disease occurrence, development, and prognosis. Excessive immune activation can induce severe myocardial injury and lead to fulminant myocarditis,whereas chronic inflammation can lead to cardiac remodelling and inflammatory dilated cardiomyopathy. The use of immunosuppressive treatments, particularly cytotoxic agents, for myocarditis, remains controversial. While reasonable and effective immunomodulatory therapy is the general trend. This review focuses on the current understanding of the aetiology and immunopathogenesis of myocarditis and offers new perspectives on immunomodulatory therapies.
基金support of the Yaque del Norte Water Fund(FAYN),INTEC(Grant No.CBA-330810-2020-P-1)Fondo Dominicano de Ciencia y Tecnologia(FONDOCYT)(Grant No.2022-2B2-161)。
文摘Constructed wetlands(CwW)are well known nature-based systems for water treatment.This study evaluated the efficiency and effectiveness of seven domestic wastewater treatment systems based on horizontal flow CWs in Jarabacoa,the Dominican Republic.The results showed that the CWs were efficient in reducing the degree of contamination of wastewater to levels below the Dominican wastewater discharge standards for parameters such as the 5-day biochemical oxygen demand(BOD5)and chemical oxygen demand,but not for the removal of phosphorus and fecal coliforms.In addition,a horizontal flow subsurface wetland in the peri-urban area El Dorado was evaluated in terms of the performance of wastewater treatment in tropical climatic conditions.The concentrations of heavy metals,such as zinc,copper,chromium,and iron,were found to decrease in the effluent of the wetland,and the concentrations for nickel and manganese tended to increase.The levels of heavy metals in the effluent were lower than the limit values of the Dominican wastewater discharge standards.The construction cost of these facilities was around 200 USD per population equivalent,similar to the cost in other countries in the same region.This study suggested some solutions to the improved performance of CWs:selection of a microbial flora that guarantees the reduction of nitrates and nitrites to molecular nitrogen,use of endemic plants that bioaccumulate heavy metals,combination of constructed wetlands with filtration on activated carbon,and inclusion of water purification processes that allow to evaluate the reuse of treated water.
基金This work was supported by the National Key Research andDevelopment Programof China(2021YFD1800200 and2021YFC2301700).
文摘The stamping-out strategy has been used to control highly pathogenic avian influenza viruses in many countries,driven by the belief that vaccination would not be successful against such viruses and fears that avian influenza virus in vaccinated birds would evolve more rapidly and pose a greater risk to humans.In this review,we summarize the successes in controlling highly pathogenic avian influenza in China and make suggestions regarding the requirements for vaccine selection and effectiveness.In addition,we present evidence that vaccination of poultry not only eliminates human infection with avian influenza virus,but also significantly reduces and abolishes some harmful characteristics of avian influenza virus.
基金the Guangdong Major Project of Basic and Applied Basic Research(2020B0301030007).
文摘Bordetella bronchiseptica(Bb)is recognized as a leading cause of respiratory diseases in dogs and cats.However,epidemiological data on Bb in dogs and cats in China are still limited,and there is no commercially available vaccine.Live vaccines containing Bb that are widely used abroad are generally efective but can establish latency and potentially reactivate to cause illness in some immunodefcient vaccinated recipients,raising safety concerns.In this study,34 canine-derived and two feline-derived Bb strains were isolated from 1809 canine and 113 feline nasopharyngeal swab samples collected from eight provinces in China from 2021 to 2023.The PCR results showed that the percentage of positive Bb was 22.94%(441/1922),and more than 90%of the Bb isolates had four virulence factor-encoding genes(VFGs),namely,fhaB,prn,betA and dnt.All the isolated strains displayed a multidrug-resistant phenotype.The virulence of 10 Bb strains isolated from dogs with respiratory symptoms was tested in mice,and we found that eight isolates were highly virulent.Furthermore,the eight Bb isolates with high virulence were inactivated and intramuscularly injected into mice,and three Bb strains(WH1218,WH1203 and WH1224)with the best protective efcacy were selected.Dogs immunized with these three strains exhibited strong protection against challenge with the Bb feld strain WH1218.Ultimately,the WH1218 strain with the greatest protection in dogs was selected as the vaccine candidate.Dogs and cats that received a vaccine containing 109 CFU of the inactivated WH1218 strain showed complete protection against challenge with the Bb feld strain WH1218.This study revealed that Bb is an important pathogen that causes respiratory diseases in domestic dogs and cats in China,and all the isolates exhibited multidrug resistance.The present work contributes to the current understanding of the prevalence,antimicrobial resistance,and virulence genes of Bb in domestic dogs and cats.Additionally,our results suggest that the WH1218 strain is a promising candidate safe and efcacious inactivated Bb vaccine.
基金funded by the National Science Centre,Poland(Project No.:2017/26/D/NZ6/00136).
文摘Pathogenic microorganisms produce numerous metabolites,including volatile organic compounds(VOCs).Monitoring these metabolites in biological matrices(e.g.,urine,blood,or breath)can reveal the presence of specific microorganisms,enabling the early diagnosis of infections and the timely implementation of tar-geted therapy.However,complex matrices only contain trace levels of VOCs,and their constituent com-ponents can hinder determination of these compounds.Therefore,modern analytical techniques enabling the non-invasive identification and precise quantification of microbial VOCs are needed.In this paper,we discuss bacterial VOC analysis under in vitro conditions,in animal models and disease diagnosis in humans,including techniques for offline and online analysis in clinical settings.We also consider the advantages and limitations of novel microextraction techniques used to prepare biological samples for VOC analysis,in addition to reviewing current clinical studies on bacterial volatilomes that address inter-species in-teractions,the kinetics of VOC metabolism,and species-and drug-resistance specificity.
基金supported by the National Natural Science Foundation of China Young Scholars Project(31902242)the Agricultural Science and Technology Innovation Program(ASTIP)of Chinese Academy of Agricultural Sciences(2017–2020)。
文摘Avian pathogenic Escherichia coli(APEC)belonging to extraintestinal pathogenic E.coli(ExPEC)can cause severe infections in extraintestinal tissues in birds and humans,such as the lungs and blood.MprA(microcin production regulation,locus A,herein renamed AbsR,a blood survival regulator),a member of the MarR(multiple antibiotic resistance regulator)transcriptional regulator family,governs the expression of capsule biosynthetic genes in human ExPEC and represents a promising druggable target for antimicrobials.However,a deep understanding of the AbsR regulatory mechanism as well as its regulon is lacking.In this study,we present a systems-level analysis of the APEC AbsR regulon using ChIP-Seq(chromatin immunoprecipitation sequencing)and RNA-Seq(RNA sequencing)methods.We found that AbsR directly regulates 99 genes and indirectly regulates 667 genes.Furthermore,we showed that:1)AbsR contributes to antiphagocytotic effects by macrophages and virulence in a mouse model for systemic infection by directly activating the capsular gene cluster;2)AbsR positively impacts biofilm formation via direct regulation of the T2SS(type II secretion system)but plays a marginal role in virulence;and 3)AbsR directly upregulates the acid tolerance signaling system EvgAS to withstand acid stress but is dispensable in ExPEC virulence.Finally,our data indicate that the role of AbsR in virulence gene regulation is relatively conserved in ExPEC strains.Altogether,this study provides a comprehensive analysis of the AbsR regulon and regulatory mechanism,and our data suggest that AbsR likely influences virulence primarily through the control of capsule production.Interestingly,we found that AbsR severely represses the expression of the type I-F CRISPR(clustered regularly interspaced short palindromic repeats)-Cas(CRISPR associated)systems,which could have implications in CRISPR biology and application.
基金financially supported by the National Nature Science Foundation of China (32372077)the Project of Chongqing Science and Technology Commission (CSTB2023NSCQ-MSX0355)the Fundamental Research Funds for the Central Universities (SWU120075)。
文摘The necrotrophic fungus, Sclerotinia sclerotiorum, employs an array of cell wall-degrading enzymes(CWDEs), including cellulase, to dismantle host cell walls. However, the molecular mechanisms through which S. sclerotiorum degrades cellulose remain elusive. Here, we unveil a novel secretory cellobiohydrolase, SsdchA, characterized by a signal peptide and a Glyco_hydro_7(GH7) domain. SsdchA exhibits a robust expression of during early infection stages. Interestingly, colony morphology and growth rates remain unaffected across the wild-type, SsdchA deletion strains and SsdchA overexpression strains on potato dextrose agar(PDA) medium. Nevertheless, the pathogenicity and cellobiohydrolase activity decreased in the SsdchA deletion strains, but enhanced in the SsdchA overexpression strains. Moreover,the heterologous expression of SsdchA in Arabidopsis thaliana leads to reduced cellulose content and heightened susceptibility to S. sclerotiorum. Collectively, our data underscore the pivotal role of the novel cellobiohydrolase SsdchA in the pathogenicity of S. sclerotiorum.
