scholarly journals A Chlamydial Plasmid-Dependent Secretion System for the Delivery of Virulence Factors to the Host Cytosol

mBio ◽  
2021 ◽  
Author(s):  
Lei Lei ◽  
Chunfu Yang ◽  
Michael John Patton ◽  
Margery Smelkinson ◽  
David Dorward ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Virulence Factors ◽  
Immune Evasion ◽  
Secretion System ◽  
Unknown Mechanism ◽  
Content Type ◽  
Plasmid Gene

The Chlamydia trachomatis plasmid regulates the expression and secretion of immune evasion virulence factors to the host cytosol by an unknown mechanism. In this study, we identified a novel plasmid gene protein 4 (Pgp4)-dependent secretion system.

scholarly journals Non-O1/Non-O139 Vibrio cholerae Carrying Multiple Virulence Factors and V. cholerae O1 in the Chesapeake Bay, Maryland

2015 ◽  
Vol 81 (6) ◽  
pp. 1909-1918 ◽  
Author(s):  
Daniela Ceccarelli ◽  
Arlene Chen ◽  
Nur A. Hasan ◽  
Shah M. Rashed ◽  
Anwar Huq ◽  
...  
Keyword(s):  
Chesapeake Bay ◽  
Vibrio Cholerae ◽  
Virulence Factors ◽  
Fluorescent Antibody ◽  
Secretion System ◽  
Surveillance Program ◽  
Toxin Gene ◽  
Protease Gene ◽  
Content Type ◽  
Pathogenic Variants

ABSTRACTNon-O1/non-O139Vibrio choleraeinhabits estuarine and coastal waters globally, but its clinical significance has not been sufficiently investigated, despite the fact that it has been associated with septicemia and gastroenteritis. The emergence of virulent non-O1/non-O139V. choleraeis consistent with the recognition of new pathogenic variants worldwide. Oyster, sediment, and water samples were collected during a vibrio surveillance program carried out from 2009 to 2012 in the Chesapeake Bay, Maryland.V. choleraeO1 was detected by a direct fluorescent-antibody (DFA) assay but was not successfully cultured, whereas 395 isolates of non-O1/non-O139V. choleraewere confirmed by multiplex PCR and serology. Only a few of the non-O1/non-O139V. choleraeisolates were resistant to ampicillin and/or penicillin. Most of the isolates were sensitive to all antibiotics tested, and 77 to 90% carried the El Tor variant hemolysin genehlyAET, the actin cross-linking repeats in toxin genertxA, the hemagglutinin protease genehap, and the type 6 secretion system. About 19 to 21% of the isolates carried the neuraminidase-encoding genenanHand/or the heat-stable toxin (NAG-ST), and only 5% contained a type 3 secretion system. None of the non-O1/non-O139V. choleraeisolates containedVibriopathogenicity island-associated genes. However,ctxA,ace, orzotwas present in nine isolates. Fifty-five different genotypes showed up to 12 virulence factors, independent of the source of isolation, and represent the first report of both antibiotic susceptibility and virulence associated with non-O1/non-O139V. choleraefrom the Chesapeake Bay. Since these results confirm the presence of potentially pathogenic non-O1/non-O139V. cholerae, monitoring for totalV. cholerae, regardless of serotype, should be done within the context of public health.

scholarly journals Genomic Avenue to Avian Colisepticemia

mBio ◽  
2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Sagi Huja ◽  
Yaara Oren ◽  
Eva Trost ◽  
Elzbieta Brzuszkiewicz ◽  
Dvora Biran ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Genetic Analysis ◽  
Virulence Factors ◽  
Iron Uptake ◽  
Secretion System ◽  
Economic Losses ◽  
Content Type ◽  
E Coli ◽  
Type 3 Secretion System ◽  
Type 3

ABSTRACTHere we present an extensive genomic and genetic analysis of Escherichia coli strains of serotype O78 that represent the major cause of avian colisepticemia, an invasive infection caused by avian pathogenicEscherichia coli(APEC) strains. It is associated with high mortality and morbidity, resulting in significant economic consequences for the poultry industry. To understand the genetic basis of the virulence of avian septicemic E. coli, we sequenced the entire genome of a clinical isolate of serotype O78—O78:H19 ST88 isolate 789 (O78-9)—and compared it with three publicly available APEC O78 sequences and one complete genome of APEC serotype O1 strain. Although there was a large variability in genome content between the APEC strains, several genes were conserved, which are potentially critical for colisepticemia. Some of these genes are present in multiple copies per genome or code for gene products with overlapping function, signifying their importance. A systematic deletion of each of these virulence-related genes identified three systems that are conserved in all septicemic strains examined and are critical for serum survival, a prerequisite for septicemia. These are the plasmid-encoded protein, the defective ETT2 (E. colitype 3 secretion system 2) type 3 secretion system ETT2sepsis, and iron uptake systems. Strain O78-9 is the only APEC O78 strain that also carried the regulon coding for yersiniabactin, the iron binding system of theYersiniahigh-pathogenicity island. Interestingly, this system is the only one that cannot be complemented by other iron uptake systems under iron limitation and in serum.IMPORTANCEAvian colisepticemia is a severe systemic disease of birds causing high morbidity and mortality and resulting in severe economic losses. The bacteria associated with avian colisepticemia are highly antibiotic resistant, making antibiotic treatment ineffective, and there is no effective vaccine due to the multitude of serotypes involved. To understand the disease and work out strategies to combat it, we performed an extensive genomic and genetic analysis of Escherichia coli strains of serotype O78, the major cause of the disease. We identified several potential virulence factors, conserved in all the colisepticemic strains examined, and determined their contribution to growth in serum, an absolute requirement for septicemia. These findings raise the possibility that specific vaccines or drugs can be developed against these critical virulence factors to help combat this economically important disease.

scholarly journals Derivatives of Plant Phenolic Compound Affect the Type III Secretion System of Pseudomonas aeruginosa via a GacS-GacA Two-Component Signal Transduction System

2011 ◽  
Vol 56 (1) ◽  
pp. 36-43 ◽  
Author(s):  
Akihiro Yamazaki ◽  
Jin Li ◽  
Quan Zeng ◽  
Devanshi Khokhani ◽  
William C. Hutchins ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Phenolic Compounds ◽  
Virulence Factors ◽  
Type Iii Secretion ◽  
Small Rnas ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Human Pathogen ◽  
Content Type ◽  
Type Iii

ABSTRACTAntibiotic therapy is the most commonly used strategy to control pathogenic infections; however, it has contributed to the generation of antibiotic-resistant bacteria. To circumvent this emerging problem, we are searching for compounds that target bacterial virulence factors rather than their viability.Pseudomonas aeruginosa, an opportunistic human pathogen, possesses a type III secretion system (T3SS) as one of the major virulence factors by which it secretes and translocates T3 effector proteins into human host cells. The fact that this human pathogen also is able to infect several plant species led us to screen a library of phenolic compounds involved in plant defense signaling and their derivatives for novel T3 inhibitors. Promoter activity screening ofexoS, which encodes a T3-secreted toxin, identified two T3 inhibitors and two T3 inducers ofP. aeruginosaPAO1. These compounds alterexoStranscription by affecting the expression levels of the regulatory small RNAs RsmY and RsmZ. These two small RNAs are known to control the activity of carbon storage regulator RsmA, which is responsible for the regulation of the key T3SS regulator ExsA. As RsmY and RsmZ are the only targets directly regulated by GacA, our results suggest that these phenolic compounds affect the expression ofexoSthrough the GacSA-RsmYZ-RsmA-ExsA regulatory pathway.

scholarly journals The Whole-Genome Sequence of Plasmid-Bearing Staphylococcus argenteus Strain B3-25B from Retail Beef Liver Encodes the Type VII Secretion System and Several Virulence Factors

2019 ◽  
Vol 8 (45) ◽  
Author(s):  
Leena Neyaz ◽  
Anand B. Karki ◽  
Mohamed K. Fakhr
Keyword(s):  
Virulence Factors ◽  
Genome Sequence ◽  
Secretion System ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Circular Chromosome ◽  
Beef Liver ◽  
Content Type ◽  
Type Vii Secretion ◽  
Type Vii Secretion System

The whole-genome sequence of Staphylococcus argenteus strain B3-25B, isolated from retail beef liver, comprises a circular chromosome (2,676,222 bp) and a single plasmid (21,570 bp). The chromosome harbors genes encoding the type VII secretion system and several virulence factors.

scholarly journals The Type IX Secretion System Is Required for Virulence of the Fish Pathogen Flavobacterium psychrophilum

2020 ◽  
Vol 86 (16) ◽  
Author(s):  
Paul Barbier ◽  
Tatiana Rochat ◽  
Haitham H. Mohammed ◽  
Gregory D. Wiens ◽  
Jean-François Bernardet ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Gene Deletion ◽  
Cold Water ◽  
Secretion System ◽  
Gliding Motility ◽  
Control Measures ◽  
Fish Pathogen ◽  
Wild Type ◽  
Content Type ◽  
Bacterial Cold Water Disease

ABSTRACT Flavobacterium psychrophilum causes bacterial cold-water disease in wild and aquaculture-reared fish and is a major problem for salmonid aquaculture. The mechanisms responsible for cold-water disease are not known. It was recently demonstrated that the related fish pathogen, Flavobacterium columnare, requires a functional type IX protein secretion system (T9SS) to cause disease. T9SSs secrete cell surface adhesins, gliding motility proteins, peptidases, and other enzymes, any of which may be virulence factors. The F. psychrophilum genome has genes predicted to encode components of a T9SS. Here, we used a SacB-mediated gene deletion technique recently adapted for use in the Bacteroidetes to delete a core F. psychrophilum T9SS gene, gldN. The ΔgldN mutant cells were deficient for secretion of many proteins in comparison to wild-type cells. Complementation of the mutant with wild-type gldN on a plasmid restored secretion. Compared to wild-type and complemented strains, the ΔgldN mutant was deficient in adhesion, gliding motility, and extracellular proteolytic and hemolytic activities. The ΔgldN mutant exhibited reduced virulence in rainbow trout and complementation restored virulence, suggesting that the T9SS plays an important role in the disease. IMPORTANCE Bacterial cold-water disease, caused by F. psychrophilum, is a major problem for salmonid aquaculture. Little is known regarding the virulence factors involved in this disease, and control measures are inadequate. A targeted gene deletion method was adapted to F. psychrophilum and used to demonstrate the importance of the T9SS in virulence. Proteins secreted by this system are likely virulence factors and targets for the development of control measures.

scholarly journals The Haemophilus ducreyi Fis Protein Is Involved in Controlling Expression of thelspB-lspA2Operon and Other Virulence Factors

2013 ◽  
Vol 81 (11) ◽  
pp. 4160-4170 ◽  
Author(s):  
Maria Labandeira-Rey ◽  
Dana A. Dodd ◽  
Chad A. Brautigam ◽  
Kate R. Fortney ◽  
Stanley M. Spinola ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Regulatory System ◽  
Structural Similarity ◽  
Enteric Bacteria ◽  
Secretion System ◽  
Haemophilus Ducreyi ◽  
Altered Expression ◽  
Content Type ◽  
Genes Encoding ◽  
Regulatory Effects

ABSTRACTExpression of thelspB-lspA2operon encoding a virulence-related two-partner secretion system inHaemophilus ducreyi35000HP is directly regulated by the CpxRA regulatory system (M. Labandeira-Rey, J. R. Mock, and E. J. Hansen, Infect. Immun. 77:3402–3411, 2009). In the present study, we show that this secretion system is also regulated by the small nucleoid-associated protein Fis. Inactivation of theH. ducreyi fisgene resulted in a reduction in expression of both theH. ducreyiLspB and LspA2 proteins. DNA microarray experiments showed that aH. ducreyi fisdeletion mutant exhibited altered expression levels of genes encoding other importantH. ducreyivirulence factors, including DsrA and Flp1, suggesting a possible global role for Fis in the control of virulence in this obligate human pathogen. While theH. ducreyiFis protein has a high degree of sequence and structural similarity to the Fis proteins of other bacteria, its temporal pattern of expression was very different from that of enterobacterial Fis proteins. The use of alacZ-based transcriptional reporter provided evidence which indicated that theH. ducreyiFis homolog is a positive regulator ofgyrB, a gene that is negatively regulated by Fis in enteric bacteria. Taken together, the Fis protein expression data and the observed regulatory effects of Fis inH. ducreyisuggest that this small DNA binding protein has a regulatory role inH. ducreyiwhich may differ in substantial ways from that of other Fis proteins.

scholarly journals Discovery of Plant Phenolic Compounds That Act as Type III Secretion System Inhibitors or Inducers of the Fire Blight Pathogen, Erwinia amylovora

2013 ◽  
Vol 79 (18) ◽  
pp. 5424-5436 ◽  
Author(s):  
Devanshi Khokhani ◽  
Chengfang Zhang ◽  
Yan Li ◽  
Qi Wang ◽  
Quan Zeng ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Virulence Factors ◽  
Type Iii Secretion ◽  
Fire Blight ◽  
Erwinia Amylovora ◽  
Fluorescent Protein ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Content Type ◽  
Type Iii

ABSTRACTErwinia amylovoracauses a devastating disease called fire blight in rosaceous plants. The type III secretion system (T3SS) is one of the important virulence factors utilized byE. amylovorain order to successfully infect its hosts. By using a green fluorescent protein (GFP) reporter construct combined with a high-throughput flow cytometry assay, a library of phenolic compounds and their derivatives was studied for their ability to alter the expression of the T3SS. Based on the effectiveness of the compounds on the expression of the T3SS pilus, the T3SS inhibitors 4-methoxy-cinnamic acid (TMCA) and benzoic acid (BA) and one T3SS inducer,trans-2-(4-hydroxyphenyl)-ethenylsulfonate (EHPES), were chosen for further study. Both the T3SS inhibitors (TMCA and BA) and the T3SS inducer (EHPES) were found to alter the expression of T3SS through the HrpS-HrpL pathway. Additionally, TMCA altered T3SS expression through thersmBEa-RsmAEasystem. Finally, we found that TMCA and BA weakened the hypersensitive response (HR) in tobacco by suppressing the T3SS ofE. amylovora. In our study, we identified phenolic compounds that specifically targeted the T3SS. The T3SS inhibitor may offer an alternative approach to antimicrobial therapy by targeting virulence factors of bacterial pathogens.

scholarly journals Esx Paralogs Are Functionally Equivalent to ESX-1 Proteins but Are Dispensable for Virulence inMycobacterium marinum

2018 ◽  
Vol 200 (11) ◽  
Author(s):  
Rachel E. Bosserman ◽  
Cristal Reyna Thompson ◽  
Kathleen R. Nicholson ◽  
Patricia A. Champion
Keyword(s):  
Virulence Factors ◽  
Ex Vivo ◽  
Secretion System ◽  
Mycobacterium Marinum ◽  
Host Cells ◽  
Duplicated Genes ◽  
Disease Etiology ◽  
Content Type ◽  
M Genome

ABSTRACTMycobacterium marinumis a nontuberculous pathogen of poikilothermic fish and an opportunistic human pathogen. Like tuberculous mycobacteria, theM. marinumM strain requires the ESX-1 (ESAT-6 system 1) secretion system for virulence in host cells. EsxB and EsxA, two major virulence factors exported by the ESX-1 system, are encoded by theesxBAgenes within the ESX-1 locus. Deletion of theesxBAgenes abrogates ESX-1 export and attenuatesM. marinuminex vivoandin vivomodels of infection. Interestingly, there are several duplications of theesxBandesxAgenes (esxB_1,esxB_2,esxA_1,esxA_2, andesxA_3) in theM. marinumM genome located outside the ESX-1 locus. We sought to understand if this region, known as ESX-6, contributes to ESX-1-mediated virulence. We found that deletion of theesxB_1gene alone or the entire ESX-6 locus did not impact ESX-1 export or function, supporting the idea that theesxBAgenes present at the ESX-1 locus are the primary contributors to ESX-1-mediated virulence. Nevertheless, overexpression of theesxB_1locus complemented ESX-1 function in the ΔesxBAstrain, signifying that the two loci are functionally equivalent. Our findings raise questions about why duplicate versions of theesxBAgenes are maintained in theM. marinumM genome and how these proteins, which are functionally equivalent to virulence factors, contribute to mycobacterial biology.IMPORTANCEMycobacterium tuberculosisis the causative agent of the human disease tuberculosis (TB). There are 10.4 million cases and 1.7 million TB-associated deaths annually, making TB a leading cause of death globally. Nontuberculous mycobacteria (NTM) cause chronic human infections that are acquired from the environment. Despite differences in disease etiology, both tuberculous and NTM pathogens use the ESX-1 secretion system to cause disease. The nontubercular mycobacterial species,Mycobacterium marinum, has additional copies of specific ESX-1 genes. Our findings demonstrate that the duplicated genes do not contribute to virulence but can substitute for virulence factors inM. marinum. These findings suggest that the duplicated genes may play a specific role in NTM biology.

scholarly journals Hypervirulent Chlamydia trachomatis Clinical Strain Is a Recombinant between Lymphogranuloma Venereum (L2) and D Lineages

mBio ◽  
2011 ◽  
Vol 2 (3) ◽  
Author(s):  
Naraporn Somboonna ◽  
Raymond Wan ◽  
David M. Ojcius ◽  
Matthew A. Pettengill ◽  
Sandeep J. Joseph ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Virulence Factors ◽  
The United States ◽  
Lymphogranuloma Venereum ◽  
Genetic Exchange ◽  
Clinical Strain ◽  
Toxin Gene ◽  
Content Type ◽  
Hemorrhagic Proctitis ◽  
Sex With Men

ABSTRACTChlamydia trachomatisis an obligate intracellular bacterium that causes a diversity of severe and debilitating diseases worldwide. Sporadic and ongoing outbreaks of lymphogranuloma venereum (LGV) strains among men who have sex with men (MSM) support the need for research on virulence factors associated with these organisms. Previous analyses have been limited to single genes or genomes of laboratory-adapted reference strain L2/434 and outbreak strain L2b/UCH-1/proctitis. We characterized an unusual LGV strain, termed L2c, isolated from an MSM with severe hemorrhagic proctitis. L2c developed nonfusing, grape-like inclusions and a cytotoxic phenotype in culture, unlike the LGV strains described to date. Deep genome sequencing revealed that L2c was a recombinant of L2and D strains with conserved clustered regions of genetic exchange, including a 78-kb region and a partial, yet functional, toxin gene that was lost with prolonged culture. Indels (insertions/deletions) were discovered in anftsKgene promoter and in thetarpandhctBgenes, which encode key proteins involved in replication, inclusion formation, and histone H1-like protein activity, respectively. Analyses suggest that these indels affect gene and/or protein function, supporting thein vitroand disease phenotypes. While recombination has been known to occur forC. trachomatisbased on gene sequence analyses, we provide the first whole-genome evidence for recombination between a virulent, invasive LGV strain and a noninvasive common urogenital strain. Given the lack of a genetic system for producing stableC. trachomatismutants, identifying naturally occurring recombinants can clarify gene function and provide opportunities for discovering avenues for genomic manipulation.IMPORTANCELymphogranuloma venereum (LGV) is a prevalent and debilitating sexually transmitted disease in developing countries, although there are significant ongoing outbreaks in Australia, Europe, and the United States among men who have sex with men (MSM). Relatively little is known about LGV virulence factors, and only two LGV genomes have been sequenced to date. We isolated an LGV strain from an MSM with severe hemorrhagic proctitis that was morphologically unique in tissue culture compared with other LGV strains. Bioinformatic and statistical analyses identified the strain as a recombinant of L2and D strains with highly conserved clustered regions of genetic exchange. The unique culture morphology and, more importantly, disease phenotype could be traced to the genes involved in recombination. The findings have implications for bacterial species evolution and, in the case of ongoing LGV outbreaks, suggest that recombination is a mechanism for strain emergence that results in significant disease pathology.

scholarly journals Transcriptional Silencing by TsrA in the Evolution of Pathogenic Vibrio cholerae Biotypes

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Florence Caro ◽  
José A. Caro ◽  
Nicole M. Place ◽  
John J. Mekalanos
Keyword(s):  
Gene Expression ◽  
Vibrio Cholerae ◽  
Virulence Factors ◽  
Virulence Genes ◽  
Secretion System ◽  
Type Vi Secretion System ◽  
Content Type ◽  
Type Vi Secretion ◽  
Genes Encoding ◽  
El Tor

ABSTRACT Vibrio cholerae is a globally important pathogen responsible for the severe epidemic diarrheal disease called cholera. The current and ongoing seventh pandemic of cholera is caused by El Tor strains, which have completely replaced the sixth-pandemic classical strains of V. cholerae. To successfully establish infection and disseminate to new victims, V. cholerae relies on key virulence factors encoded on horizontally acquired genetic elements. The expression of these factors relies on the regulatory architecture that coordinates the timely expression of virulence determinants during host infection. Here, we apply transcriptomics and structural modeling to understand how type VI secretion system regulator A (TsrA) affects gene expression in both the classical and El Tor biotypes of V. cholerae. We find that TsrA acts as a negative regulator of V. cholerae virulence genes encoded on horizontally acquired genetic elements. The TsrA regulon comprises genes encoding cholera toxin (CT), the toxin-coregulated pilus (TCP), and the type VI secretion system (T6SS), as well as genes involved in biofilm formation. The majority of the TsrA regulon is carried on horizontally acquired AT-rich genetic islands whose loss or acquisition could be directly ascribed to the differences between the classical and El Tor strains studied. Our modeling predicts that the TsrA protein is a structural homolog of the histone-like nucleoid structuring protein (H-NS) oligomerization domain and is likely capable of forming higher-order superhelical structures, potentially with DNA. These findings describe how TsrA can integrate into the intricate V. cholerae virulence gene expression program, controlling gene expression through transcriptional silencing. IMPORTANCE Pathogenic Vibrio cholerae strains express multiple virulence factors that are encoded by bacteriophage and chromosomal islands. These include cholera toxin and the intestinal colonization pilus called the toxin-coregulated pilus, which are essential for causing severe disease in humans. However, it is presently unclear how the expression of these horizontally acquired accessory virulence genes can be efficiently integrated with preexisting transcriptional programs that are presumably fine-tuned for optimal expression in V. cholerae before its conversion to a human pathogen. Here, we report the role of a transcriptional regulator (TsrA) in silencing horizontally acquired genes encoding important virulence factors. We propose that this factor could be critical to the efficient acquisition of accessory virulence genes by silencing their expression until other signals trigger their transcriptional activation within the host.

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