Molecular Basis of Bacterial Defense against Host Lysozymes: X-ray Structures of Periplasmic Lysozyme Inhibitors PliI and PliC

Leysen, S.; Herreweghe, J.M. Van; Callewaert, Lien; Heirbaut, Michelle; Buntinx, P.; Michiels, Chris W.; Strelkov, S.V.

doi:10.1016/j.jmb.2010.12.007

Cited by 28 publications

(34 citation statements)

References 38 publications

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“…Supplementary Figure 3 presents small-angle X-ray scattering data that is consistent with a monomeric structure in solution. What is most interesting about the X-Tfi XAC2610 structure is that among its closest topological homologues are the periplasmic I-type lysozyme inhibitor PliI 25,26 (Fig. 3b) and the P. aeruginosa immunity protein Tsi1 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Bacterial killing via a type IV secretion system

et al. 2015

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Section: Resultsmentioning

confidence: 99%

Bacterial killing via a type IV secretion system

et al. 2015

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“…This supposition is based on three observations: (i) the hidden Markov matches of LipA and LipB are closer to PliC than to the membrane-bound MliC lysozyme inhibitors; (ii) PliC proteins tend to have a longer loop (loop 5) between ␤ strands 5 and 6 (65), and this region aligns well with both LipA and LipB (Fig. 5); and (iii) the MliC proteins are lipoproteins, but there is no apparent lipidation signal in either LipA or LipB.…”

Section: Discussionmentioning

confidence: 99%

A Moraxella catarrhalis Two-Component Signal Transduction System Necessary for Growth in Liquid Media Affects Production of Two Lysozyme Inhibitors

et al. 2015

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There are a paucity of data concerning gene products that could contribute to the ability of Moraxella catarrhalis to colonize the human nasopharynx. Inactivation of a gene (mesR) encoding a predicted response regulator of a two-component signal transduction system in M. catarrhalis yielded a mutant unable to grow in liquid media. This mesR mutant also exhibited increased sensitivity to certain stressors, including polymyxin B, SDS, and hydrogen peroxide. Inactivation of the gene (mesS) encoding the predicted cognate sensor (histidine) kinase yielded a mutant with the same inability to grow in liquid media as the mesR mutant. DNA microarray and real-time reverse transcriptase PCR analyses indicated that several genes previously shown to be involved in the ability of M. catarrhalis to persist in the chinchilla nasopharynx were upregulated in the mesR mutant. Two other open reading frames upregulated in the mesR mutant were shown to encode small proteins (LipA and LipB) that had amino acid sequence homology to bacterial adhesins and structural homology to bacterial lysozyme inhibitors. Inactivation of both lipA and lipB did not affect the ability of M. catarrhalis O35E to attach to a human bronchial epithelial cell line in vitro. Purified recombinant LipA and LipB fusion proteins were each shown to inhibit human lysozyme activity in vitro and in saliva. A lipA lipB deletion mutant was more sensitive than the wild-type parent strain to killing by human lysozyme in the presence of human apolactoferrin. This is the first report of the production of lysozyme inhibitors by M. catarrhalis. Moraxella catarrhalis is a Gram-negative coccobacillus that can cause disease in both the upper and lower respiratory tracts of humans (1). In infants and young children, this bacterium is a significant cause of acute otitis media (i.e., middle ear infection) (2-4). In adults, M. catarrhalis can cause infectious exacerbations of chronic obstructive pulmonary disease (COPD) (5-7) and is likely responsible for approximately 4 million exacerbations of COPD annually in the United States (6). The latter disease has global significance because it has been predicted that by 2020, COPD will become the third leading cause of death worldwide (reviewed in reference 8). In addition, M. catarrhalis can cause sinusitis, pneumonia, and, more rarely, bacteremia (1, 9).M. catarrhalis colonization of the human nasopharynx is apparently asymptomatic and, at least in infancy, can be correlated with an increased risk of otitis media (10). In this anatomic niche, M. catarrhalis likely forms a biofilm, together with the normal bacterial flora of the nasopharynx (11, 12). Once established in the nasopharynx, this bacterium can spread to the middle ear (causing otitis media) or to the lower respiratory tract (resulting in an infectious exacerbation of COPD). A number of putative M. catarrhalis colonization or virulence factors have been described in the past decade (13-20), but identification of those bacterial gene products that are truly essential for nasop...

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“…Lysozyme-inhibitory activity of rMliC. Since lysozyme inhibitors in their natural forms are usually difficult to obtain, especially with relatively high purity, these proteins have been studied in the form of recombinant proteins (13,17,20,21,32). In our study, to examine the biological activity of MliC Et , rMliC was purified from E. coli as a Trx-tagged protein.…”

Section: Sequence Of Mlic Etmentioning

confidence: 99%

“…These inhibitors are known as inhibitor of vertebrate lysozyme (Ivy) proteins, which target C-type lysozyme, periplasmic lysozyme inhibitor of C-type lysozyme (PliC), membrane-associated lysozyme inhibitor of Ctype lysozyme (MliC), periplasmic inhibitor of I-type lysozyme (PliI), and periplasmic inhibitor of G-type lysozyme (PliG) (13)(14)(15)(16)(17). Of these inhibitors, MliC/PliC have been found in various bacterial species, and high-resolution structures of the MliCs/ PliCs of Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica serovar Typhimurium, and Brucella abortus have been reported (18)(19)(20)(21). It seems that MliC proteins fall into two subgroups, which differ in dimer formation.…”

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

Wang

Sun

2015

Infect Immun

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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 Ivy Et 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 singleknockout 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.

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Molecular Basis of Bacterial Defense against Host Lysozymes: X-ray Structures of Periplasmic Lysozyme Inhibitors PliI and PliC

Cited by 28 publications

References 38 publications

Bacterial killing via a type IV secretion system

Bacterial killing via a type IV secretion system

A Moraxella catarrhalis Two-Component Signal Transduction System Necessary for Growth in Liquid Media Affects Production of Two Lysozyme Inhibitors

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

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