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At least 19 recordsLinked to original sources
PubMed2002

Role of the Hha/YmoA family of proteins in the thermoregulation of the expression of virulence factors.

Virulent bacteria are able to sense temperature changes and respond by modifying the expression of--among others--genes that code for virulence factors. The chromatin-associated protein H-NS has been shown to play a role in the thermomodulation of virulence factor expression. In addition to H-NS, proteins of the Hha/YmoA family have also been identified in different enterobacteria as participating in the thermoregulation of some virulence factors. For one of these proteins, the Hha protein, it has been shown that it interacts with H-NS, and both proteins form a nucleoid-protein complex responsible for the thermoregulation of, at least, E. coli hemolysin. The presence of genes coding for homologues of both proteins on some conjugative plasmids and their relation to thermoregulation suggests that this complex could also play a role in the regulation of plasmid transfer.

Amino Acid Sequence↗
PubMed1999

Pseudomonas aeruginosa strains obtained from patients with tracheal, urinary tract and wound infection: variations in virulence factors and virulence genes.

Pseudomonas aeruginosa produces several virulence factors including exotoxin A, exoenzyme S and elastase. In previous reports we have analysed several clinical isolates for the production of these three virulence factors and for possible heterogeneity within the genes that code for these factors (toxA, lasB and the exoS genes). The isolates were obtained from three specific sites (trachea, urinary tract and wounds). Although the isolates produced variable levels of these factors, isolates that were obtained specifically from urinary tract and wound infections produced increased levels of exotoxin A and exoenzyme S. In addition, a prolonged infection with P. aeruginosa appears to enhance exoenzyme S production. Restriction site polymorphism was very limited within the toxA, lasB, and exoS structural genes; however, the upstream region of toxA showed restriction site polymorphisms between the different isolates. The observed polymorphisms did not correlate with any variations in the levels of the virulence factors. In this article, we provide a short review of these studies.

ADP Ribose Transferases↗
PubMed1992

Roles of Listeria monocytogenes virulence factors in survival: virulence factors distinct from listeriolysin are needed for the organism to survive an early neutrophil-mediated host defense mechanism.

Avirulent mutant strains of Listeria monocytogenes which fail to produce phosphatidylinositol-specific phospholipase C, or which produce reduced amounts of hemolytic listeriolysin O, are incapable of causing progressive infection in normal mice. However, both strains can grow progressively in mice that have been rendered incapable of focusing neutrophils at sites of infection as a result of being treated with monoclonal antibody 5C6, specific for the type 3 complement receptor of myelomonocytic cells. In 5C6-treated mice, phospholipase C-negative and listeriolysin-defective mutant strains of L. monocytogenes, like the wild-type strain, give rise in the liver to large numbers of discrete foci of infected hepatocytes that retain their morphological integrity during the first 24 h, despite their large bacterial burden. In normal mice, in contrast, sites of infection in the liver are indicated by discrete focal accumulations of neutrophils that occupy the space originally occupied by infected hepatocytes. It is apparent that in normal mice neutrophils function to lyse infected hepatocytes and thereby to release L. monocytogenes for ingestion and killing by neutrophils themselves and by macrophages. However, whereas a proportion of wild-type organisms survive this early mechanism of defense to give rise to progressive infection, the phospholipase C-negative organisms are totally eliminated. On the basis of these and other results, it is suggested that virulence factors other than listeriolysin are needed by L. monocytogenes to counteract the early neutrophil-mediated mechanism of defense. Listeriolysin, itself, is an intrinsic virulence factor that allows L. monocytogenes to survive and multiply in a proportion of the fixed phagocytes of the liver (permissive phagocytes) and which enables the organism to go on to infect and replicate in adjacent hepatocytes. It was found that a mutant strain of L. monocytogenes incapable of producing any listeriolysin was incapable of establishing progressive infection, even in 5C6-treated mice.

Animals↗
PubMed1997

Glucose-1-phosphate utilization by Listeria monocytogenes is PrfA dependent and coordinately expressed with virulence factors.

Virulence genes of the facultative intracellular pathogen Listeria monocytogenes are coordinately regulated by the activator protein PrfA, encoded by prfA, a member of the cyclic AMP receptor protein family of bacterial transcription factors. We found that prfA* mutants that constitutively overexpress the virulence regulon due to a Gly145Ser substitution in PrfA (M.-T. Ripio, G. Domínguez-Bernal, M. Lara, M. Suárez, and J.-A. Vázquez-Boland, J. Bacteriol. 179:1533-1540, 1997) rapidly utilized glucose-1-phosphate (G-1-P) as a carbon source for growth, in contrast to wild-type strains, which characteristically do not. Wild-type strains acquired the capacity for readily metabolizing G-1-P upon exposure to environmental conditions that activate the expression of prfA and PrfA-dependent virulence genes (i.e., culture at 37 degrees C in charcoal-treated medium). In these strains, G-1-P utilization followed an expressional pattern identical to that of virulence genes controlled by PrfA, with repression at 20 degrees C. Tn917 insertions in L. monocytogenes mutants selected for G-1-P utilization deficiency mapped to the plcA-prfA operon, a deltaprfA strain was totally unable to utilize G-1-P, and trans complementation with prfA constructs restored the ability to efficiently metabolize and grow on G-1-P to these mutants. Thus, G-1-P utilization by L. monocytogenes is under the tight positive control of the central virulence regulator, PrfA, and is coexpressed with PrfA-dependent pathogenicity determinants. It was recently reported that readily utilized carbohydrates, such as glucose or cellobiose, repress virulence genes in L. monocytogenes. We confirmed this but, interestingly, found that G-1-P does not inhibit expression of the PrfA regulon, indicating that this sugar follows a catabolic pathway that bypasses the repressor mechanism triggered by other readily metabolized carbon sources. PrfA dependence and coexpression with virulence genes suggest that utilization of exogenous G-1-P may be relevant to Listeria pathogenesis. G-1-P is the precursor metabolite and primary degradation product of glycogen and is therefore available within the mammalian cell. Based on our results, we hypothesize that G-1-P could play an important role as a growth substrate for intracellular Listeria.

Amino Acid Substitution↗
PubMed2001

Laccase of Cryptococcus neoformans is a cell wall-associated virulence factor.

Virulence is the outcome of an interaction between the host and a microbe and is characterized by a large array of opposing reactions operating at the host-pathogen interface. Cryptococcus neoformans is an important opportunistic pathogen in immunocompromised patients, including those with human immunodeficiency virus, and expresses a virulence-associated laccase which is believed to oxidize brain catecholamines and iron as a defense against host immune cells. In the present report, we investigated the cellular location of laccase to understand more fully how it contributes to cryptococcal virulence. A monoclonal antibody to the C. neoformans laccase was generated and used to show localization in the cell walls of representative serotype A (H99) and serotype D (B-3501) strains by immunoelectron microscopy. In addition, confocal microscopy was used to show a peripheral location of green fluorescent protein-tagged laccase expressed in live H99 cells. Biochemical studies showed that laccase could be released from intact cells or cell wall fractions with glucanase enzymes but was retained in the cell wall after sequential extraction with 1 M NaCl, 6 M urea, and 1% sodium dodecyl sulfate. The presence of a hydrolyzable bond linking laccase to the cell wall was suggested by removal of laccase from cell wall preparations after they were boiled in 1% sodium dodecyl sulfate, as was the presence of a disulfide or thioester bond by removal with dithiothreitol or beta-mercaptoethanol. These data show that laccase is present as a tightly associated cell wall enzyme that is readily accessible for interactions with host immune cells.

Animals↗
PubMed1979

Relationship between antibiotic resistance, the production of "virulence factors", and virulence for experimental animals in Staphylococcus aureus.

Variants that had lost some of their antibiotic-resistance determinants were selected from a multiple-antibiotic-resistant strain of Staphylococcus aureus. When tested by subcutaneous injection into guinea-pigs, and measured as the number of cocci needed to produce a skin lesion of an arbitrarily chosen diameter, the virulence of strains fell progressively with loss of resistance determinants. When the staphylococci were injected intracutaneously into mice, however, the results were less easy to interpret, but loss of resistance appeared to be associated with a reduction of the slope of the dose-response line. There was no association between the antibiogram of the strains and their production of certain enzymes and haemolysins.

Animals↗
PubMed1983

Urinary tract infectivity or R strains of Escherichia coli carrying various virulence factors.

The virulence factors of Escherichia coli supposed to act in urinary tract infections were studied on R strains in a suckling mouse model. The production of alpha-(diffusible-) haemolysin or the possession of antigen K1 enhanced the virulence significantly, while the type 1 (common) fimbriae failed to do so. An isogenic motile and non-motile pair of E. coli did not show any difference in infectivity in the model. The adhesins, the diffusible haemolysin, and the acidic polysaccharide K antigens (K1) are definitely additive virulence factors in the model. This is in good agreement with the experience of clinical bacteriology.

Animals↗
PubMedDate not supplied

The lipopolysaccharide of Shigella bacteria as a virulence factor.

The virulence factors of the lipopolysaccharide of Shigella species bacteria include the endotoxic activities of the lipid A component of the molecule and the ability of the polysaccharide chain--the core and the O-antigenic polysaccharide--to provide the bacterium with resistance to host defense mechanisms such as opsonization, phagocytosis, and intracellular killing. Structural features of the lipopolysaccharides of four Shigella species-S. dysenteriae, S. flexneri, S. boydii, and S. sonnei--are described.

Carbohydrate Sequence↗
PubMed1995

P-fimbriation and haemolysin production are the most important virulence factors in diabetic patients with Escherichia coli bacteraemia: a multivariate statistical analysis of seven bacterial virulence factors.

Diabetic patients, as compared to non-diabetic subjects, run an increased risk of acquiring Gram-negative bacteraemia. We therefore studied the prevalence and coexpression of seven bacterial virulence markers of 69 Escherichia coli strains isolated from 64 bacteraemic patients with diabetes mellitus and 67 E. coli strains from faeces of healthy controls. The strains were analyzed for haemolysin (HLY) production, aerobactin-mediated iron uptake (AMI), cytotoxic necrotizing factor (CNF) production, expression of cell surface hydrophobicity, P-fimbriae, mannose-resistant haemagglutination (MRHA) and mannose-sensitive haemagglutination (MSHA). All bacterial properties were significantly more common among the bacteraemic strains (P < 0.02 vs. controls). Correlations between HLY and CNF (P < 0.0004) and between P-fimbriae and MRHA (P < 0.0001), MSHA (P < 0.0002) or AMI (P < 0.05), as well as between MRHA and MSHA (P < 0.0005) were observed. In patients with proteinuria, as sign of diabetic complications in the urinary tract, HLY-negative strains, P-fimbriae-negative strains, and strains which were both HLY-/CNF-negative, were more common (P = 0.04, P < 0.01 and P = 0.048, respectively). Using a multivariate statistical analysis, production of HLY and the expression of P-fimbriae were the two virulence factors with the highest discrimination between bacteraemic and control strains. In conclusion, all virulence factors studied were more prevalent in bacteraemic than in control strains, although HLY and P-fimbriae were shown to be of greatest and independent importance. Low virulent strains (P-fimbriae-, HLY- and CNF-negative) were more prevalent in diabetic patients with signs of renal complications.

Adult↗
PubMed2006

Serum opacity factor, a streptococcal virulence factor that binds to apolipoproteins A-I and A-II and disrupts high density lipoprotein structure.

Serum opacity factor (SOF) is a virulence determinant of group A streptococci that opacifies mammalian sera. We analyzed the specificity and mechanism of the opacity reaction using a recombinant form of the amino-terminal opacification domain of SOF, rSOF. Our data indicate that rSOF is neither a protease nor a lipase, but rather it is the binding of rSOF to high density lipoprotein (HDL) that triggers the opacity reaction. rSOF did not opacify plasma from apoA-I(-/-) mice or purified low or very low density lipoproteins but readily opacified HDL. rSOF binding to HDL was characterized by two high affinity binding sites; it bound to apoA-I (K(d) = 6 nm) and apoA-II (K(d) = 30 nm), and both apoA-I and apoA-II blocked the binding of rSOF to HDL. Electron microscopic examination and biochemical analyses of HDL treated with rSOF revealed the formation of lipid droplets devoid of apolipoproteins. Thus, SOF interacts with HDL in human blood by binding to apoA-I and apoA-II and causing the release of HDL lipid cargo, which coalesces to form lipid droplets, resulting in opacification. The disruption of HDL may attenuate its anti-inflammatory functions and contribute to the pathogenesis of group A streptococcal infections.

Animals↗
PubMed2004

Enteroaggregative Escherichia coli virulence factors are found to be associated with infantile diarrhea in Brazil.

We have previously shown that enteroaggregative Escherichia coli (EAEC) is an important pathogen among Brazilian infants. Most EAEC strains harbor a plasmid (pAA) from which a DNA fragment has been used as a probe (EAEC probe). To better understand the characteristics of EAEC in Brazil, 109 strains carrying and lacking the EAEC probe sequence were tested for the presence of pAA plasmid-borne and chromosomal factors. Common virulence factors of probe-positive and probe-negative isolates included the presence of the Pet, EAST-1, Shf, Irp2, ShET1/Pic, and Hly virulence markers. The presence of AggR or one other virulence factor (AAF/I, AAF/II, AAF/III, or Aap) was predominantly identified only in probe-positive strains. In EAEC probe-positive strains, the virulence marker Aap was found significantly more frequently (P = 0.023) in isolates from children with diarrhea (22%) than in isolates from controls (3%). EAST-1 and Shf were the markers most frequently detected (61%) in EAEC probe-negative strains and were found to be significantly associated with diarrhea (P = 0.003 and P = 0.020, respectively). Furthermore, our data suggest that AggR can be used as an important genetic marker for EAEC probe-positive strains.

Bacterial Typing Techniques↗
PubMed2000

The Yersinia protein kinase A is a host factor inducible RhoA/Rac-binding virulence factor.

The pathogenic yersiniae inject proteins directly into eukaryotic cells that interfere with a number of cellular processes including phagocytosis and inflammatory-associated host responses. One of these injected proteins, the Yersinia protein kinase A (YpkA), has previously been shown to affect the morphology of cultured eukaryotic cells as well as to localize to the plasma membrane following its injection into HeLa cells. Here it is shown that these activities are mediated by separable domains of YpkA. The amino terminus, which contains the kinase domain, is sufficient to localize YpkA to the plasma membrane while the carboxyl terminus of YpkA is required for YpkAs morphological effects. YpkAs carboxyl-terminal region was found to affect the levels of actin-containing stress fibers as well as block the activation of the GTPase RhoA in Yersinia-infected cells. We show that the carboxyl-terminal region of YpkA, which contains sequences that bear similarity to the RhoA-binding domains of several eukaryotic RhoA-binding kinases, directly interacts with RhoA as well as Rac (but not Cdc42) and displays a slight but measurable binding preference for the GDP-bound form of RhoA. Surprisingly, YpkA binding to RhoA(GDP) affected neither the intrinsic nor guanine nucleotide exchange factor-mediated GDP/GTP exchange reaction suggesting that YpkA controls activated RhoA levels by a mechanism other than by simply blocking guanine nucleotide exchange factor activity. We go on to show that YpkAs kinase activity is neither dependent on nor promoted by its interaction with RhoA and Rac but is, however, entirely dependent on heat-sensitive eukaryotic factors present in HeLa cell extracts and fetal calf serum. Collectively, our data show that YpkA possesses both similarities and differences with the eukaryotic RhoA/Rac-binding kinases and suggest that the yersiniae utilize the Rho GTPases for unique activities during their interaction with eukaryotic cells.

Actins↗
PubMed2001

Virulence factors of Mycobacterium bovis.

Virulence factors of Mycobacterium bovis are the special properties that enable it to infect, survive, multiply and cause disease in an animal host. An understanding of these factors will lead to new strategies including an effective vaccine to control bovine tuberculosis. A few factors have already been identified and two broadly different approaches to discover other virulence factors are now being used. In the first approach, libraries of random M. bovis mutants are produced, the likely attenuated mutants are identified using a screening technique and the interrupted genes in selected mutants are identified. In the second approach, genes encoding putative virulence factors are selected by a range of different methods and then inactivated, usually by allelic exchange, to produce likely attenuated mutants of M. bovis. In both approaches, loss of virulence by a mutant must be determined in an animal model. Subsequently, the mutant must be complemented back to virulence with an active form of the identified gene in order to demonstrate that loss of virulence was not due to polar effects of the mutation on nearby genes. It is almost certain that most of the virulence factors of M. bovis are the same as those of the classical human tuberculosis organism, Mycobacterium tuberculosis, as both organisms can cause identical clinical disease in humans and are genetically very similar. Many putative virulence genes are now being investigated and only the inherent slowness with which mycobacterial work proceeds, delays the inevitable arrival of an exciting new phase in the understanding of mycobacterial disease.

Alleles↗
PubMed1997

A Gly145Ser substitution in the transcriptional activator PrfA causes constitutive overexpression of virulence factors in Listeria monocytogenes.

Virulence genes in Listeria monocytogenes are coordinately expressed under the control of the transcriptional activator PrfA, encoded by prfA, a member of the cyclic AMP (cAMP) receptor protein (CRP)/FNR family of bacterial regulators. Strain P14-A is a spontaneous mutant of L. monocytogenes serovar 4b which produces elevated levels of virulence factors (M. T. Ripio, G. Domínguez-Bernal, M. Suárez, K. Brehm, P. Berche, and J. A. Vázquez-Boland, Res. Microbiol. 147:371-384, 1996). Here we report that P14-A and other variant strains with the same phenotype carry a point mutation in codon 145 of prfA, leading to a Gly-->Ser substitution. trans-complementation experiments with PrfA-deficient mutants demonstrated that the Gly145Ser prfA allele causes overexpression of virulence factors in L. monocytogenes, to the levels found in the virulence factor-overexpressing variants. In strain P14-A with a chromosomal Glyl45Ser prfA background, transcription of prfA and of PrfA-dependent virulence genes remained constitutively high under culture conditions in which virulence factor expression is downregulated in wild-type L. monocytogenes. The Glyl45Ser substitution is located in a PrfA stretch (residues 141 to 151) showing high sequence similarity to the D alpha-helix of CRP. Interestingly, well-characterized crp* mutations, which make CRP functionally active in the absence of cAMP, map in this region (i.e., Gly141Ser and Ala144Thr substitutions). By analogy with the CRP model, the phenotype conferred to L. monocytogenes by the Gly145Ser substitution in PrfA could be due to the mutant regulatory protein being locked in a transcriptionally active, cofactor-independent conformational state. Our observations allow the construction of a model for PrfA-dependent virulence gene regulation in which the levels of virulence factor expression depend primarily on the conformational state of the PrfA protein, which alternates between active and inactive forms according to its interaction with an environmentally regulated signal molecule or cofactor.

Amino Acid Sequence↗
PubMed1994

Proliferation of a bovine mammary epithelial cell line in the presence of bacterial virulence factors.

Effects of bacterial virulence factors on bovine mammary cell structure and function are not well defined. In this study, we evaluated the influence of specific bacterial virulence factors on proliferation of a bovine mammary epithelial cell line. The MAC-T cells were cultured in the presence of medium only, Staphylococcus aureus alpha-toxin, Staph. aureus beta-toxin, Escherichia coli endotoxin, Streptococcus uberis capsule, or hyaluronidase. Cells were cultured in the presence of virulence factors for 48 h at 37 degrees C. The MAC-T cell proliferation was inhibited by all concentrations of endotoxin and alpha-toxin and by most concentrations of hyaluronic acid capsule and hyaluronidase > 7.8 micrograms/ml. Staphylococcus aureus beta-toxin had no effect on MAC-T cell proliferation. Virulence factors produced by mastitis pathogens may influence mammary epithelial cell proliferation in vivo, which could be important during the periparturient period, when mammary tissue undergoes rapid differentiation and growth.

Analysis of Variance↗
PubMedDate not supplied

A novel family of channel-forming, autotransporting, bacterial virulence factors.

Pathogenic bacteria produce virulence factors that cross the bacterial cell envelope from the cytoplasm to the extracellular milieu where they promote disease. The mechanisms of their export are poorly understood. We here characterize a family of autotransporter (AT) protein domains present at the C-termini of several nonhomologous Gram-negative bacterial virulence factors. The family consist of 18 sequenced protein domains, the functionally characterized members of which catalyze export of (1) proteases, (2) virulence-related cell adhesins, (3) mediators of actin-promoted bacterial motility, (4) cytotoxins and (5) tissue invasion proteins. We (1) establish that these AT domains are homologous, (2) multiply align their sequences, (3) derive an AT family-specific signature sequence, and (4) define the evolutionary relationships between members of the family. Secondary structural predictions as well as average hydropathy, average similarity and average amphipathicity plots have allowed us to propose a specific 14 beta-stranded barrel structural model that may be applicable to all protein members of the AT family. We suggest that the AT domains became associated with active virulence factor domains by interdomain fusion events that occurred during the evolution of these complex proteins.

Adhesins, Bacterial↗