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Edwardsiella tarda MliC, a lysozyme inhibitor that participates in pathogenesis in a manner that parallels Ivy.

ABSTRACT: Edwardsiella tarda, a bacterial pathogen to farmed fish as well as humans, possesses the genes of two lysozyme inhibitors, ivy and mliC (ivy(Et) and mliC(Et)). We recently studied IvyEt and found it to be implicated in E. tarda virulence. In the present study, we characterized MliC(Et) in comparison with Ivy(Et) in a turbot model. MliC(Et) contains the FWSKG motif and two cysteines (C33 and C98) that are highly conserved in subgroup 1 MliCs but are of unknown functional importance. To examine the essentialness of these conserved structural features, recombinant MliC(Et) (rMliC) and its mutants bearing C33S and W79A (of the FWSKG motif) substitutions were prepared. Subsequent analysis showed that rMliC (i) inhibited lysozyme-induced lysis of a Gram-positive bacterium, (ii) reduced serum-facilitated lysozyme killing of E. tarda, and (iii) when introduced into turbot, promoted bacterial dissemination in fish tissues. The C33S mutation had no influence on the activity of rMliC, while the W79A mutation slightly but significantly enhanced the activity of rMliC. Knockout strains of either mliC(Et) or ivy(Et) were severely attenuated for the ability of tissue invasion, host lethality, serum survival, and intracellular replication. The lost virulence of the mliC transformant (TX?mliC) was restored by complementation with an introduced mliC(Et) gene. Compared to the ?ivy(Et) or ?mliC(Et) single-knockout strains, the ?mliC(Et) ?ivy(Et) double-knockout strain was significantly impaired in most of the virulence features. Together, these results provide the first evidence that the conserved cysteine is functionally dispensable to a subgroup 1 MliC and that as a virulence factor, MliC(Et) most likely works in a concerted and parallel manner with Ivy.

SUBMITTER: Li MF

PROVIDER: S-EPMC4294240 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Edwardsiella tarda MliC, a lysozyme inhibitor that participates in pathogenesis in a manner that parallels Ivy.

Li Mo-Fei MF Wang Chong C Sun Li L

Infection and immunity 20141117 2

Edwardsiella tarda, a bacterial pathogen to farmed fish as well as humans, possesses the genes of two lysozyme inhibitors, ivy and mliC (ivy(Et) and mliC(Et)). We recently studied IvyEt and found it to be implicated in E. tarda virulence. In the present study, we characterized MliC(Et) in comparison with Ivy(Et) in a turbot model. MliC(Et) contains the FWSKG motif and two cysteines (C33 and C98) that are highly conserved in subgroup 1 MliCs but are of unknown functional importance. To examine th ...[more]

PMID: 25404031

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Project description:UnlabelledEdwardsiella tarda is an important pathogenic bacterium that can replicate in macrophages. However, how the intramacrophage infection process affects the virulence of this bacterium is essentially unknown. Here, we show that E. tarda replicates and induces a caspase-1-dependent cell pyroptosis in a murine macrophage model. Via pyroptosis, intracellular E. tarda escapes to the extracellular milieu, forming a unique bacterial population. Being different from the bacteria cultured alone, this unique population possesses a reprogrammed transcriptional profile, particularly with upregulated type III secretion system (T3SS)/T6SS cluster genes. Subsequent studies revealed that the macrophage-released population gains enhanced infectivity for host epithelial cells and increases resistance to multiple host defenses and hence displays significantly promoted virulence in vivo Further studies indicated that T3SS is essentially required for the macrophage infection process, while T6SS contributes to infection-induced bacterial virulence. Altogether, this work demonstrates that E. tarda can utilize macrophages as a niche for virulence priming and for spreading infection, suggesting a positive role for intramacrophage infection in bacterial pathogenesis.ImportanceMany pathogens can replicate in macrophages, which is crucial for their pathogenesis. To survive in the macrophage cell, pathogens are likely to require fitness genes to counteract multiple host-killing mechanisms. Here, Edwardsiella tarda is proved to exit from macrophages during infection. This macrophage-released population displays a reprogrammed transcriptional profile with significantly upregulated type III secretion system (T3SS)/T6SS-related genes. Furthermore, both enhanced infectivity in epithelial cells and activated resistance to complex host defenses were conferred on this macrophage-primed population, which consequently promoted the full virulence of E. tarda in vivo Our work provides evidence that E. tarda can utilize macrophages as a niche for virulence priming and for spreading infection, highlighting the importance of the intramacrophage infection cycle for the pathogenesis of E. tarda.

Dataset Information

Edwardsiella tarda MliC, a lysozyme inhibitor that participates in pathogenesis in a manner that parallels Ivy.

Publications

Edwardsiella tarda MliC, a lysozyme inhibitor that participates in pathogenesis in a manner that parallels Ivy.

Similar Datasets

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