Jones Megan M, Johnson Antoinette, Koszelak-Rosenblum Mary, Kirkham Charmaine, Brauer Aimee L, Malkowski Michael G, Murphy Timothy F
Department of Microbiology and Immunology, University at Buffalo, The State University of New York, Buffalo, New York, USA Clinical and Translational Research Center, University at Buffalo, The State University of New York, Buffalo, New York, USA.
Clinical and Translational Research Center, University at Buffalo, The State University of New York, Buffalo, New York, USA Division of Infectious Diseases, Department of Medicine, University at Buffalo, The State University of New York, Buffalo, New York, USA.
Infect Immun. 2014 Nov;82(11):4758-66. doi: 10.1128/IAI.02185-14. Epub 2014 Aug 25.
Moraxella catarrhalis is a strict human pathogen that causes otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults, resulting in significant worldwide morbidity and mortality. M. catarrhalis has a growth requirement for arginine; thus, acquiring arginine is important for fitness and survival. M. catarrhalis has a putative oligopeptide permease ABC transport operon (opp) consisting of five genes (oppB, oppC, oppD, oppF, and oppA), encoding two permeases, two ATPases, and a substrate binding protein. Thermal shift assays showed that the purified recombinant substrate binding protein OppA binds to peptides 3 to 16 amino acid residues in length regardless of the amino acid composition. A mutant in which the oppBCDFA gene cluster is knocked out showed impaired growth in minimal medium where the only source of arginine came from a peptide 5 to 10 amino acid residues in length. Whether methylated arginine supports growth of M. catarrhalis is important in understanding fitness in the respiratory tract because methylated arginine is abundant in host tissues. No growth of wild-type M. catarrhalis was observed in minimal medium in which arginine was present only in methylated form, indicating that the bacterium requires l-arginine. An oppA knockout mutant showed marked impairment in its capacity to persist in the respiratory tract compared to the wild type in a mouse pulmonary clearance model. We conclude that the Opp system mediates both uptake of peptides and fitness in the respiratory tract.
卡他莫拉菌是一种严格的人类病原体,可导致儿童中耳炎和成人慢性阻塞性肺疾病急性加重,在全球范围内造成显著的发病率和死亡率。卡他莫拉菌生长需要精氨酸;因此,获取精氨酸对其适应性和生存至关重要。卡他莫拉菌有一个假定的寡肽通透酶ABC转运操纵子(opp),由五个基因(oppB、oppC、oppD、oppF和oppA)组成,编码两种通透酶、两种ATP酶和一种底物结合蛋白。热迁移分析表明,纯化的重组底物结合蛋白OppA与长度为3至16个氨基酸残基的肽结合,而不考虑氨基酸组成。oppBCDFA基因簇被敲除的突变体在基本培养基中生长受损,在该培养基中,精氨酸的唯一来源是长度为5至10个氨基酸残基的肽。甲基化精氨酸是否支持卡他莫拉菌的生长对于理解其在呼吸道中的适应性很重要,因为甲基化精氨酸在宿主组织中含量丰富。在仅以甲基化形式存在精氨酸的基本培养基中未观察到野生型卡他莫拉菌生长,这表明该细菌需要L-精氨酸。在小鼠肺部清除模型中,与野生型相比,oppA基因敲除突变体在呼吸道中持续存在的能力明显受损。我们得出结论,Opp系统介导肽的摄取以及在呼吸道中的适应性。