Periplasmic Cu, Zn-cofactored superoxide dismutase (SodC) protects Gram-negative bacteria from exogenous oxidative damage. The virulent Salmonella typhimurium strain ATCC 14028s has been found to contain two discrete periplasmic Cu, Zn-SOD enzymes that are only 57% identical at the amino acid level. SodCI is carried by a cryptic bacteriophage, and SodCII is closely related to the Cu, Znsuperoxide dismutase of Escherichia coli. All Salmonella serotypes appear to carry the sodCII locus, but the phageassociated sodCI gene is found only in certain strains belonging to the most highly pathogenic serotypes. Expression of either sodC locus appears to be enhanced during stationary phase, but only sodCII is regulated by the alternative sigma factor s (RpoS). Mutants lacking both sodC genes are less lethal for mice than mutants possessing either sodC locus alone, indicating that both Cu, Zn-SOD enzymes contribute to Salmonella pathogenicity. The evolutionary acquisition of an additional sodC gene has contributed to the enhanced virulence of selected Salmonella strains.
SummaryThe opportunistic pathogen Enterococcus faecalis is well equipped with peroxidatic activities. It harbours three loci encoding a NADH peroxidase, an alkyl hydroperoxide reductase and a protein (EF2932) belonging to the AhpC/TSA family. We present results demonstrating that ef2932 does encode a thiol peroxidase (Tpx) and show that it is part of the regulon of the hydrogen peroxide regulator HypR. Characterization of unmarked deletion mutants showed that all three peroxidases are important for the defence against externally provided H 2O2. Exposure to internal generated H2O2 by aerobic growth on glycerol, lactose, galactose or ribose showed that Npr was absolutely required for aerobic growth on glycerol and optimal growth on the other substrates. Growth on glycerol was also dependent on Ahp. Addition of catalase restored growth of the mutants, and therefore, extracellular H2O2 concentrations have been determined. This showed that the time point of growth arrest of the Dnpr mutant correlated with the highest H2O2 concentration measured. Analysis of the survival of the different strains inside peritoneal macrophages revealed that Tpx was the most important antioxidant activity for protecting the cells against the hostile phagocyte environment. Finally, the Dtpx and the triple mutant showed attenuated virulence in a mouse peritonitis model.
Background Enterococcus faecalis is one of the leading agents of nosocomial infections. To cause diseases, pathogens or opportunistic bacteria have to adapt and survive to the defense systems encountered in the host. One of the most important compounds of the host innate defense response against invading microorganisms is lysozyme. It is found in a wide variety of body fluids, as well as in cells of the innate immune system. Lysozyme could act either as a muramidase and/or as a cationic antimicrobial peptide. Like Staphylococcus aureus, E. faecalis is one of the few bacteria that are completely lysozyme resistant.ResultsThis study revealed that oatA (O-acetyl transferase) and dlt (D-Alanylation of lipoteicoic acids) genes contribute only partly to the lysozyme resistance of E. faecalis and that a specific transcriptional regulator, the extracytoplasmic function SigV sigma factor plays a key role in this event. Indeed, the sigV single mutant is as sensitive as the oatA/dltA double mutant, and the sigV/oatA/dltA triple mutant displays the highest level of lysozyme sensitivity suggesting synergistic effects of these genes. In S. aureus, mutation of both oatA and dlt genes abolishes completely the lysozyme resistance, whereas this is not the case in E. faecalis. Interestingly SigV does not control neither oatA nor dlt genes. Moreover, the sigV mutants clearly showed a reduced capacity to colonize host tissues, as they are significantly less recovered than the parental JH2-2 strain from organs of mice subjected to intravenous or urinary tract infections.ConclusionsThis work led to the discovery of an original model of lysozyme resistance mechanism which is obviously more complex than those described for other Gram positive pathogens. Moreover, our data provide evidences for a direct link between lysozyme resistance and virulence of E. faecalis.
Enterococcus faecalis is an opportunistic pathogen that causes numerous infectious diseases in humans and is a major agent of nosocomial infections. In this work, we showed that the recently identified transcriptional regulator Ers (PrfA like), known to be involved in the cellular metabolism and the virulence of E. faecalis, acts as a repressor of ace, which encodes a collagen-binding protein. We characterized the promoter region of ace, and transcriptional analysis by reverse transcription-quantitative PCR and mobility shift protein-DNA binding assays revealed that Ers directly regulates the expression of ace. Transcription of ace appeared to be induced by the presence of bile salts, probably via the deregulation of ers. Moreover, with an ace deletion mutant and the complemented strain and by using an insect (Galleria mellonella) virulence model, as well as in vivo-in vitro murine macrophage models, we demonstrated for the first time that Ace can be considered a virulence factor for E. faecalis. Furthermore, animal experiments revealed that Ace is also involved in urinary tract infection by E. faecalis.Enterococcus faecalis is a natural member of the intestinal microflora of warm-blooded animals and humans. However, E. faecalis remains an important opportunistic pathogen and represents one of the principal causes of nosocomial infections in the United States and Europe (33; for a review, see reference 20). Especially for immunocompromised patients, these infections include endocarditis, meningitis, pneumonia, peritonitis, visceral abscesses, urinary infections, and septicemia (13). About a dozen putative virulence factors have been identified in E. faecalis, but mechanisms of virulence remain not fully understood. These factors are involved in different steps of the infection process, such as attachment to host cells or extracellular matrix (ECM), macrophage resistance, tissue damage, and immune system evasion (20).For extracellular pathogens such as E. faecalis or Staphylococcus aureus, components of ECM or serum (i.e., collagen, fibronectin, and fibrinogen) are preferred targets for adhesion. During important steps of the infectious process, they interact with bacterial surface-exposed molecules, which include microbial surface components recognizing adhesive matrix molecules (MSCRAMMs). Ace, an adhesin that binds collagen (types I and IV) and laminin and belongs to the MSCRAMM family, was identified in E. faecalis by sequence homology with the virulence factor Cna, a well-characterized MSCRAMM in S. aureus (16,26). Synthesis of the A domain of Ace by S. aureus increased its arthritogenic potential to a level similar to that of S. aureus expressing Cna (34). Study of the sequence diversity of ace among several strains of E. faecalis has revealed an important variation in the number of repeated sequences (17). However, the role played by these regions has not yet been elucidated. The expression of Ace is significantly induced by high temperature (culture at 46°C) and in vivo by the presence of serum or ECM com...
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