Edwardsiella tarda MliC, a Lysozyme Inhibitor That Participates in Pathogenesis in a Manner That Parallels Ivy release_nbn56v4etjhotpn4vy42duiypm

by Mo-Fei Li, Chong Wang, Li Sun

Abstract

<jats:named-content content-type="genus-species">Edwardsiella tarda</jats:named-content>, a bacterial pathogen to farmed fish as well as humans, possesses the genes of two lysozyme inhibitors,<jats:italic>ivy</jats:italic>and<jats:italic>mliC</jats:italic>(<jats:italic>ivy<jats:sub>Et</jats:sub></jats:italic>and<jats:italic>mliC<jats:sub>Et</jats:sub></jats:italic>). We recently studied Ivy<jats:sub>Et</jats:sub>and found it to be implicated in<jats:named-content content-type="genus-species">E. tarda</jats:named-content>virulence. In the present study, we characterized MliC<jats:sub>Et</jats:sub>in comparison with Ivy<jats:sub>Et</jats:sub>in a turbot model. MliC<jats:sub>Et</jats:sub>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<jats:sub>Et</jats:sub>(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<jats:named-content content-type="genus-species">E. tarda</jats:named-content>, 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<jats:italic>mliC<jats:sub>Et</jats:sub></jats:italic>or<jats:italic>ivy<jats:sub>Et</jats:sub></jats:italic>were severely attenuated for the ability of tissue invasion, host lethality, serum survival, and intracellular replication. The lost virulence of the<jats:italic>mliC</jats:italic>transformant (TXΔ<jats:italic>mliC</jats:italic>) was restored by complementation with an introduced<jats:italic>mliC<jats:sub>Et</jats:sub></jats:italic>gene. Compared to the Δ<jats:italic>ivy<jats:sub>Et</jats:sub></jats:italic>or Δ<jats:italic>mliC<jats:sub>Et</jats:sub></jats:italic>single-knockout strains, the Δ<jats:italic>mliC<jats:sub>Et</jats:sub></jats:italic>Δ<jats:italic>ivy<jats:sub>Et</jats:sub></jats:italic>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<jats:sub>Et</jats:sub>most likely works in a concerted and parallel manner with Ivy.
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Published in Infection and Immunity by American Society for Microbiology
ISSN-L 0019-9567
Volume 83
Page(s) 583-590
Release Date 2014-11-17
Publisher American Society for Microbiology
Primary Language en (lookup)

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Type  article-journal
Stage   published
Date   2014-11-17
DOI  10.1128/iai.02473-14
PubMed  25404031
PMC  PMC4294240
Wikidata  Q34955570
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