Identification of an Outer Membrane Lipoprotein Involved in Nasopharyngeal Colonization by Moraxella catarrhalis in an Animal Model

Wang, Wei; Joslin, Stephanie N.; Pybus, Christine; Evans, Amanda S.; Lichaa, Flora; Brautigam, Chad A.; Hansen, Eric J.

doi:10.1128/iai.01745-14

Cited by 8 publications

(10 citation statements)

References 81 publications

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“…Examination of data from a previous study that identified M. catarrhalis genes whose expression was upregulated when broth-grown bacteria were inoculated into the chinchilla nasopharynx (21) showed that there was little or no change in the level of mesR transcription, even though the levels of lipA and lipB transcripts increased approximately 4-fold and 1.5-fold, respectively. In M. catarrhalis bacteria that attached to human bronchial epithelial cells in vitro (80), there were very modest (i.e., 1.4-to 1.5-fold) increases in mesR, lipA, and lipB transcription levels. Further interpretation of the available regulatory data is limited by the fact that the phosphorylation, or a lack thereof, of a response regulator (i.e., MesR) greatly affects its ability to stimulate or inhibit transcriptional activity (81).…”

Section: Discussionmentioning

confidence: 99%

“…Attachment assay. The ability of wild-type and mutant strains of M. catarrhalis to attach to an immortalized human bronchial epithelial cell line (16HBE14o-) (38) in vitro was measured as described previously (22).…”

Section: Methodsmentioning

confidence: 99%

“…Inactivation of MCORF 1550 decreased the ability of M. catarrhalis O35E to colonize the chinchilla nasopharynx (21), and a lack of expression of the outer membrane lipoprotein encoded by MCORF 113 resulted in the decreased persistence of M. catarrhalis in the chinchilla nasopharynx (22). Expression of both MCORF 1550 (which increased 6-fold; Table 2) and MCORF 113 (which increased 1.7-fold; see Table S1 in the supplemental material) was upregulated in the mesR mutant.…”

Section: Structural Biology Of the M Catarrhalis Mess And Mesr Protementioning

confidence: 99%

“…To determine whether these two M. catarrhalis proteins might be involved in adherence, the lipA and lipB genes were deleted in M. catarrhalis strain O35E. The O35E strain was used for mutant construction because its genome has been sequenced (36) and because we have extensive experience in using the O35E strain in attachment assays (22,70). Western blot analysis confirmed that individual lipA and lipB mutants (Fig.…”

Section: Fig 2 Growth Characteristics Of Wild-type M Catarrhalis Etsmentioning

confidence: 99%

“…To date, the type IV pilus is the only known adhesin shown to be involved in the colonization ability of M. catarrhalis in vivo in an animal model (18). More recently, expression of both M. catarrhalis open reading frame (MCORF) 1550 (21) and MCORF 113 (22) was shown to be necessary for the optimal persistence of M. catarrhalis O35E in the chinchilla nasopharynx, although the specific function of the products encoded by the genes remains to be determined.…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%