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PubMedDate not supplied

Virulence factors of Clostridium perfringens.

Clostridium perfringens produces a variety of virulence factors. The mechanism of action of these factors usually falls into one of three groups. Some of these virulence factors, such as the alpha toxin, which is phospholipase C, and the kappa toxin, which is a collagenase, are enzymes that hydrolyze substances essential to the integrity of membranes or other body structures. Other virulence factors, such as the beta, episolon, and iota toxins, act primarily on the vascular endothelium, causing increased capillary permeability, especially in the brain. Still others, such as the delta and theta toxins, are essentially hemolysins. Theta toxin is similar in action and serologically related to streptolysin O.

Bacterial Toxins↗

PubMed1997

A two-component system in Ralstonia (Pseudomonas) solanacearum modulates production of PhcA-regulated virulence factors in response to 3-hydroxypalmitic acid methyl ester.

Expression of virulence factors in Ralstonia solanacearum is controlled by a complex regulatory network, at the center of which is PhcA, a LysR family transcriptional regulator. We report here that expression of phcA and production of PhcA-regulated virulence factors are affected by products of the putative operon phcBSR(Q). phcB is required for production of an extracellular factor (EF), tentatively identified as the fatty acid derivative 3-hydroxypalmitic acid methyl ester (3-OH PAME), but a biochemical function for PhcB could not be deduced from DNA sequence analysis. The other genes in the putative operon are predicted to encode proteins homologous to members of two-component signal transduction systems: PhcS has amino acid similarity to histidine kinase sensors, whereas PhcR and OrfQ are similar to response regulators. PhcR is quite unusual because its putative output domain strongly resembles the histidine kinase domain of a sensor protein. Production of the PhcA-regulated factors exopolysaccharide I, endoglucanase, and pectin methyl esterase was reduced 10- to 100-fold only in mutants with a nonpolar insertion in phcB [which express phcSR(Q) in the absence of the EF]; simultaneously, expression of phcA was reduced fivefold. Both a wild-type phenotype and phcA expression were restored by addition of 3-OH PAME to growing cultures. Mutants with polar insertions in phcB or lacking the entire phcBSR(Q) region produced wild-type levels of PhcA-regulated virulence factors. The genetic data suggest that PhcS and PhcR function together to regulate expression of phcA, but the biochemical mechanism for this is unclear. At low levels of the EF, it is likely that PhcS phosphorylates PhcR, and then PhcR interacts either with PhcA (which is required for full expression of phcA) or an unknown component of the signal cascade to inhibit expression of phcA. When the EF reaches a threshold concentration, we suggest that it reduces the ability of PhcS to phosphorylate PhcR, resulting in increased expression of phcA and production of PhcA-regulated factors.

Amino Acid Sequence↗

PubMed2001

The virulence factors of Bordetella pertussis: a matter of control.

Bordetella pertussis is the causative agent of whooping cough, a contagious childhood respiratory disease. Increasing public concern over the safety of whole-cell vaccines led to decreased immunisation rates and a subsequent increase in the incidence of the disease. Research into the development of safer, more efficacious, less reactogenic vaccine preparations was concentrated on the production and purification of detoxified B. pertussis virulence factors. These virulence factors include adhesins such as filamentous haemagglutinin, fimbriae and pertactin, which allow B. pertussis to bind to ciliated epithelial cells in the upper respiratory tract. Once attachment is initiated, toxins produced by the bacterium enable colonisation to proceed by interfering with host clearance mechanisms. B. pertussis co-ordinately regulates the expression of virulence factors via the Bordetella virulence gene (bvg) locus, which encodes a response regulator responsible for signal-mediated activation and repression. This strict regulation mechanism allows the bacterium to express different gene subsets in different environmental niches within the host, according to the stage of disease progression.

Animals↗

PubMed1996

Virulence factors and O groups of Escherichia coli isolates from patients with acute pyelonephritis, cystitis and asymptomatic bacteriuria.

The relationship between the presence of bacterial virulence factors and the severity of urinary tract infection (UTI) was analized in this study. The production of alpha-hemolysin (Hly), the expression of P-fimbriae and the mannose-resistant hemagglutination (MRHA) type IVa (associated with the presence of P-fimbriae), were all detected more frequently in Escherichia coli strains from acute pyelonephritis than in strains isolated from cystitis and asymptomatic bacteriuria. In contrast, the production of cytotoxic necrotizing factor type 1 (CNF1) and the expression of MRHA types III and IVb were distributed uniformly between strains causing different clinical categories of UTI. Thus 88% of the E. coli strains from acute pyelonephritis showed some of the virulence factors investigated in this study, whereas only 60% (p < 0.01) and 56% (p < 0.01) repectively of the strains isolated from cystitis and asymptomatic bacteriuria possessed virulence factors. There were no significant differences in the prevalence of virulence properties between strains isolated from patients with or without complicating factors. Only 16% (p < 0.001) of the fecal isolates from healthy individuals showed virulence factors. The virulence factors were concentrated in strains belonging to 10 (O1, O2, O4, O6, O7, O14, O18, O22, O75 and O83) of the 12 serogroups most frequently detected in uropathogenic E. coli strains. The majority of uropathogenic O4, O6, O14, O22, O75 and O83 E.coli strains were Hly+CNF1+ and expressed P-fimbriae or MRHA type III, whereas the strains of serogroup O18 were Hly+CNF1- and P-fimbriated. Among O1 and O7 strains we found Hly-CNF1-strains that expressed P-fimbriae. Among O2 strains we found Hly+CNF1+ strains that expressed P-fimbriae or MRHA type III and other Hly-CNF1-strains that possessed P-fimbriae. We conclude that E.coli strains isolated from pyelonephritis show virulence factors more frequently than those from cystitis and asymptomatic bacteriuria, and that strains that cause urinary tract infections in Spain belong to the same serogroups as uropathogenic E.coli isolated in other areas of the world. Our results support the special pathogenicity theory and suggest that many cases of serious urogenital disease may be caused by a limited number of P-fimbriated E.coli strains that usually produce alpha-hemolysin.

Acute Disease↗

PubMed2000

Role of bacterial virulence factors and host factors in the outcome of Escherichia coli bacteraemia.

In a study of the role of virulence factors in the outcome of Escherichia coli bacteraemia, blood isolates from 30 hospitalised patients were characterised with regard to O and K antigens, P and type 1 fimbriae, haemolysin production, cytonecrotising factor 1 production, serum resistance, ability to activate neutrophils and resistance to killing. Patients were analysed to identify host factors contributing to morbidity and mortality. In univariate analyses the presence of a K antigen, type 1 fimbriae, absence of haemolysin production, serum resistance and resistance to killing were associated with morbidity and mortality. In multivariate analyses only the absence of haemolysin production was associated with morbidity and mortality, after taking host factors into account. These preliminary findings suggest that host factors override bacterial virulence factors in determining the course of Escherichia coli bacteraemia. The negative association between haemolysin production and clinical deterioration during Escherichia coli bacteraemia might indicate predominance of less virulent strains in patients with other risk factors for morbidity and mortality or inactivation of neutrophil products needed for host defence.

Aged↗

PubMed1994

The maltose regulon of Vibrio cholerae affects production and secretion of virulence factors.

The effects of maltose on production and secretion of virulence factors of Vibrio cholerae in strain X28214, classical biotype, and in maltose-defective transposon mutants constructed from this strain were characterized. Maltose was found to inhibit secretion of cholera toxin and to reduce production of the mannose-sensitive hemagglutinin and the soluble hemagglutinin-protease. In contrast, the amount of toxin-coregulated pilus was increased in the presence of maltose. The maltose effect was apparently mediated by genes of the maltose regulon, since inactivation of the malQ or malF gene of V. cholerae by transposon insertion was found to affect production and secretion of the same virulence factors that were responsive to maltose. The malQ and malF mutants showed, in addition, reduced virulence in an infant-mouse model. These results suggest that maltose may have a significant regulatory role in the production of virulence factors and that an intact maltose regulon is needed for full virulence of V. cholerae.

Animals↗

PubMed1999

Environmental signals modulate ToxT-dependent virulence factor expression in Vibrio cholerae.

The regulatory protein ToxT directly activates the transcription of virulence factors in Vibrio cholerae, including cholera toxin (CT) and the toxin-coregulated pilus (TCP). Specific environmental signals stimulate virulence factor expression by inducing the transcription of toxT. We demonstrate that transcriptional activation by the ToxT protein is also modulated by environmental signals. ToxT expressed from an inducible promoter activated high-level expression of CT and TCP in V. cholerae at 30 degrees C, but expression of CT and TCP was significantly decreased or abolished by the addition of 0.4% bile to the medium and/or an increase of the temperature to 37 degrees C. Also, expression of six ToxT-dependent TnphoA fusions was modulated by temperature and bile. Measurement of ToxT-dependent transcription of genes encoding CT and TCP by ctxAp- and tcpAp-luciferase fusions confirmed that negative regulation by 37 degrees C or bile occurs at the transcriptional level in V. cholerae. Interestingly, ToxT-dependent transcription of these same promoters in Salmonella typhimurium was relatively insensitive to regulation by temperature or bile. These data are consistent with ToxT transcriptional activity being modulated by environmental signals in V. cholerae and demonstrate an additional level of complexity governing the expression of virulence factors in this pathogen. We propose that negative regulation of ToxT-dependent transcription by environmental signals prevents the incorrect temporal and spatial expression of virulence factors during cholera pathogenesis.

Bacterial Outer Membrane Proteins↗

PubMed2000

Molecular analysis of the accessory gene regulator (agr) locus and balance of virulence factor expression in epidemic methicillin-resistant Staphylococcus aureus.

Potential relationships between virulence factor expression and transmissibility were assessed in epidemic methicillin-resistant Staphylococcus aureus (MRSA) clones CMRSA-1 and CMRSA-3. A major subtype of CMRSA-1 exhibited normal transcription of RNAIII, which facilitates the induction of secreted virulence factors and repression of colonization factor expression at high cell density. However, these isolates characteristically did not express alpha-toxin or protease and displayed a limited profile of secreted proteins. CMRSA-1 also expressed a novel cell surface glycoprotein and exhibited a unique polymorphism within the accessory gene regulator (agr) locus. CMRSA-3 displayed attenuated activation of RNAIII transcription, which was consistent with its higher fibronectin-binding and coagulase activity relative to sporadic MRSA or CMRSA-1 (P=.05), low protease activity, and limited profile of secreted proteins. Thus, the balance of virulence factor expression in CMRSA-1 and CMRSA-3 favors the colonization phase of infection, and CMRSA-1 possesses unique genotypic and phenotypic traits.

Bacterial Proteins↗

PubMed2006

PtxR modulates the expression of QS-controlled virulence factors in the Pseudomonas aeruginosa strain PAO1.

The production of several virulence factors by Pseudomonas aeruginosa is regulated through the hierarchical cell-density dependent quorum sensing (QS) systems las and rhl. A third component of the QS hierarchy, the Pseudomonas quinolone signal PQS, also controls the expression of several genes. We previously described P. aeruginosa PtxR as a transcriptional activator of the exotoxin A gene toxA. Here, we provide evidence that PtxR regulates the production of other virulence factors. Mutation of ptxR in PAO1 increased pyocyanin production. This increase was reduced in the presence of a ptxR plasmid. Throughout the growth cycle, PtxR reduced the expression of the pyocyanin operon phzA1-G1 but not phzA2-G2. As pyocyanin production is stringently controlled by QS, we examined the effect of PtxR on QS-related genes in PAO1. PtxR also reduced the expression of the PQS synthesis operon pqsABCDE. ptxR mutation increased the expression of the rhamnolipid synthesis gene rhlA but decreased lasB expression. The expression of the RhlI synthase gene rhlI and the production of the C(4)-HSL autoinducer were increased in the ptxR mutant, while the expression of the LasI synthase gene lasI and the production of 3OC(12)-HSL were reduced. These results suggest that PtxR negatively regulates the expression of the rhamnolipid and pyocyanin genes through rhlI and the pqsABCDE operon while it positively regulates the expression of lasB through lasI.

4-Butyrolactone↗

PubMed2005

Transcriptional profiles of regulatory and virulence factors of Staphylococcus aureus of bovine origin: oxygen impact and strain-to-strain variations.

Staphylococcus aureus is responsible for a large panel of infections in humans and animals. In cows, S. aureus provokes chronic intramammary infections. Little information is available about the regulation of virulence factors in bovine isolates. Moreover, oxygenation, which is low in an inflamed mammary gland, could play an important role during the infectious process. We investigated the impact of oxygen on regulatory and virulence factors transcription for three S. aureus bovine isolates cultivated in CYPG medium into a fermentor under moderate oxygenation or low oxygenation. A selective panel of regulatory factors and virulence factors was studied through their mRNA profiles by real-time PCR according to growth phases and oxygenation. RNAIII, rot and sarR genes, for the regulatory factors, and asp23 and cflA genes, for the virulence factors, were strongly expressed, whatever the oxygenation and the strains. Under low oxygenation, whatever the strain, an enhanced expression of srr, clfA and spa genes was detected. Some regulators such as sae, sarA and sigB were differentially transcribed according to the strain and the oxygenation condition. This study sustains the complexity of S. aureus genes global regulation and suggests the coexistence of different pathways that can be activated depending on the strain and the oxygen availability.

Animals↗

PubMed2004

Distribution of six virulence factors in Aeromonas species isolated from US drinking water utilities: a PCR identification.

AIMS: To examine whether Aeromonas bacteria isolated from municipally treated water had virulence factor genes. METHODS AND RESULTS: A polymerase chain reaction-based genetic characterization determined the presence of six virulence factors genes, elastase (ahyB), lipase (pla/lip/lipH3/alp-1) flagella A and B (flaA and flaB), the enterotoxins, act, alt and ast, in these isolates. New primer sets were designed for all the target genes, except for act. The genes were present in 88% (ahyB), 88% (lip), 59% (fla), 43% (alt), 70% (act) and 30% (ast) of the strains, respectively. Of the 205 isolates tested only one isolate had all the virulence genes. There was a variety of combinations of virulence factors within different strains of the same species. However, a dominant strain having the same set of virulence factors, was usually isolated from any given tap in different rounds of sampling from a single tap. CONCLUSIONS: These results show that Aeromonas bacteria found in drinking water possess a wide variety of virulence-related genes and suggest the importance of examining as many isolates as possible in order to better understand the health risk these bacteria may present. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents a rapid method for characterizing the virulence factors of Aeromonas bacteria and suggests that municipally treated drinking water is a source of potentially pathogenic Aeromonas bacteria.

Aeromonas↗

PubMed1991

[New findings on virulence factors in Salmonella species].

The authors present a review of the literature on most recent findings pertaining to the properties of the most important factors of virulence of Salmonellae, in particular from the aspects of their biological and physico-chemical properties. These findings can contribute towards the elucidation of factors of pathogenicity and virulence of these microbes and mechanisms of the pathogenesis of diseases they produce.

Salmonella↗

PubMed2006

Activity and expression of a virulence factor, gelatinase, in dairy enterococci.

In order to understand the virulence potential of dairy enterococci, 35 isolates from raw ewe's milk and traditionally fermented cheeses, identified as Enterococcus faecalis, Enterococcus faecium, Enterococcus durans, Enterococcus dispar and Enterococcus hirae, were screened for their capacity to produce gelatinase and for the presence of the genes gelE, sprE, fsrA, fsrB and fsrC. Studies correlating gelatinase production with maintenance and subculture of the isolates in the Laboratory environment, and growth in different media were performed. These studies were conducted with two dairy isolates identified as E. faecalis and E. durans, and one clinical isolate, E. faecalis OG1-10. RT-PCR was used for detection of transcripts of the above mentioned genes. Results demonstrated that the virulence factor gelatinase is disseminated among the genus Enterococcus and that dairy isolates are capable of producing gelatinase at comparable levels with clinical isolates, although this capacity is easily lost during conservation by freezing in the laboratory. Therefore, gelatinase production potential of dairy enterococci may be underestimated. The gene gelE was present in all studied isolates. The same was observed for the fsr operon, either complete or incomplete, revealing that the gelatinase genetic determinants, so far only described in E. faecalis, are a common trait in the genus. This work describes for the first time the detection of the complete Fsr-GelE operon in other species than E. faecalis, namely E. faecium and E. durans. The loss of expression of this virulence factor under laboratory culture conditions correlated with the loss of one or more genes of the regulatory fsr operon, although the gene gelE was maintained, demonstrating that a complete fsr operon is required for a positive GelE phenotype. Independent of the detection of any gelatinase activity, if both gelE and the complete fsr operon are present in the cell, all genes are transcribed, as revealed by RT-PCR, suggesting that regulation of gelatinase activity can also be post-transcriptional. The silent behavior of gelE was only observed in E. faecalis, but not in E. durans, suggesting different modulation mechanisms of gelatinase activity in these two species. Overall, these findings reopen the issue of food safety of enterococci and reinforce the need to further study the mechanisms responsible for triggering the virulence factor gelatinase in non-pathogenic enterococcal environmental isolates.

Animals↗

PubMed2004

Analysis of major virulence factors in Porphyromonas gingivalis under various culture temperatures using specific antibodies.

Porphyromonas gingivalis is implicated in the occurrence of adult periodontitis. We have previously identified major outer membrane proteins from P. gingivalis, which include representative virulence factors such as gingipains, a 75 kDa major protein, RagA, RagB, and putative porin. Fimbriae, another important virulence factor, exist on the cell surface. In this study, we identified major supernatant proteins. They were fimbrilin, the 75 kDa major protein, gingipains and their adhesin domains. Microscopic examination showed that supernatant proteins formed vesicle-like and fimbrial structures. To learn more about the character of this bacterium, we examined effects of growth temperature on localization and expression of these virulence factors. In general, localization of major virulence factors did not change at the various growth temperatures used. Most of the 75 kDa major protein, RagA, RagB, and putative porin were found in the envelope fraction, not in cell-free culture supernatant. Gingipains were found in both the envelope fraction and supernatant. More than 80% of fimbriae were associated with cells, less than 20% migrated to the supernatant. Most fimbriae existed in the whole cell lysate, although there was a small amount in the envelope fraction. When the growth temperature was increased, expression of fimbriae, gingipains, the 75 kDa major protein, RagA, and RagB decreased. However, temperature had almost no effect on expression of putative porin. The tendency for expression of major virulence factors to decrease at higher temperatures may enable P. gingivalis to survive under hostile conditions.

Amino Acid Sequence↗

PubMed2006

Characterizing the effect of the Staphylococcus aureus virulence factor regulator, SarA, on log-phase mRNA half-lives.

Bacterial pathogens regulate virulence factor expression at both the level of transcription initiation and mRNA processing/turnover. Within Staphylococcus aureus, virulence factor transcript synthesis is regulated by a number of two-component regulatory systems, the DNA binding protein SarA, and the SarA family of homologues. However, little is known about the factors that modulate mRNA stability or influence transcript degradation within the organism. As our entree to characterizing these processes, S. aureus GeneChips were used to simultaneously determine the mRNA half-lives of all transcripts produced during log-phase growth. It was found that the majority of log-phase transcripts (90%) have a short half-life (<5 min), whereas others are more stable, suggesting that cis- and/or trans-acting factors influence S. aureus mRNA stability. In support of this, it was found that two virulence factor transcripts, cna and spa, were stabilized in a sarA-dependent manner. These results were validated by complementation and real-time PCR and suggest that SarA may regulate target gene expression in a previously unrecognized manner by posttranscriptionally modulating mRNA turnover. Additionally, it was found that S. aureus produces a set of stable RNA molecules with no predicted open reading frame. Based on the importance of the S. aureus agr RNA molecule, RNAIII, and small stable RNA molecules within other pathogens, it is possible that these RNA molecules influence biological processes within the organism.

Bacterial Proteins↗

PubMed2004

[Virulence factors of clinical Aeromonas caviae isolates].

Aeromonas caviae, an ubiquitous aquatic organism, has long been considered to be of low pathogenicity, and its virulence mechanisms are still not clearly understood. Twenty-eight A. caviae isolates of clinical origin, most often monomicrobic, were identified in our university hospital over a four year period. Patients, mostly immunocompromised, were: eight diarrhoeal infants, 13 diarrhoeal adults, seven bacteraemic adults. Adults were frequently suffering from underlying intestinal malignancy, hepatobiliary disease, gastrectomy. Virulence factors were investigated. Adherence, studied by use of tissue culture HEp-2 cells, and staining of characteristic lateral flagella, were observed in diarrhoeal strains. Extracellular hemolytic activity was tested on rabbit erythrocytes suspensions at 25 and 37 degrees C. One blood culture isolate showed an important hemolytic activity at 25 degrees C, but none at 37 degrees C. Treatment with furin activated the aerolysin precursor and resulted in significant hemolysis at 37 degrees C, and fluid accumulation in rabbit ileal loops similar to that of A. hydrophila as control. The presence of the hemolysin gene was confirmed in this strain by PCR. In conclusion, A. caviae was shown to be a pathogen isolated from diarrhoea and bacteraemia in immunocompromised patients with malignancies and low gastric acidity as favouring factors. Virulence including the ability to adhere to cells and the production of lateral flagella was observed in diarrhoeal strains. The expression and the production of extracellular hemolytic activity and enterotoxicity at 37 degrees C depended on the activation of the pore forming toxin aerolysin precursor by furin. In vivo the protoxin is probably processed to its mature form by host proteases.

Adult↗

PubMed2005

Occurrence of virulence factors among human intestinal enterococcal isolates.

AIMS: The aim of this study was to investigate the frequency of enterococcal virulence factors among human intestinal Enterococcus faecalis strains and to find out whether the pattern differs from that seen in published reports on food and clinical isolates. METHODS AND RESULTS: The E. faecalis isolates were cultured from human faecal samples obtained from five ulcerative colitis patients in remission phase. The species identification was based on API120 strips and species-specific PCR primers. The isolates were further characterized using the pulsed-field gel electrophoresis. The presence of seven different known enterococcal virulence factors among the confirmed E. faecalis isolates were screened using PCR techniques and published primers. CONCLUSIONS: Among the 35 isolates representing nine different pulsotypes the most frequent virulence factors were cpd (33 isolates), agg (25 isolates), gelE (22 isolates) and esp (15 isolates). No complete sets of genes associated for the production of functional cytolysin were encountered indicating that intestinal enterococci may differ in this respect from clinical strains. SIGNIFICANCE AND IMPACT OF THE STUDY: According to the results, the commensal enterococcal strains appear to differ from clinical isolates in their complement of presumed virulence factors.

Adult↗

PubMed2005

Quinolone-resistant uropathogenic Escherichia coli strains from phylogenetic group B2 have fewer virulence factors than their susceptible counterparts.

The prevalence of 31 virulence factors was analyzed among nalidixic acid-susceptible and -resistant Escherichia coli strains from phylogenetic group B2. Hemolysin, cytotoxic necrotizing factor 1, and S and F1C fimbriae genes were less prevalent among nalidixic acid-resistant E. coli strains. Quinolone resistance may be associated with a decrease in the presence of some virulence factors.

Anti-Infective Agents↗