title: A Moraxella catarrhalis two-component signal transduction system necessary for growth in liquid media affects production of two lysozyme inhibitors.
abstract: 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.
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Stephanie N
authors.initials: SN
authors.lastname: Joslin
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Pybus
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Labandeira-Rey
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Evans
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Attia
authors.affiliation: Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Brautigam
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA eric.hansen@utsouthwestern.edu.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Hansen
mesh_terms: D002448:Cell Adhesion; D002460:Cell Line; D003470:Culture Media / Q000737:chemistry; D004847:Epithelial Cells / Q000382:microbiology; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005816:Genetic Complementation Test; D000071677:Histidine Kinase; D046228:Microarray Analysis; D001936:Moraxella catarrhalis / Q000254:growth & development* / Q000378:metabolism*; D009113:Muramidase / Q000037:antagonists & inhibitors*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012463:Saliva / Q000276:immunology / Q000382:microbiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D003470:Culture Media; D014157:Transcription Factors; D011494:Protein Kinases; D000071677:Histidine Kinase; D009113:Muramidase