Furano Kristin, Campagnari Anthony A
Department of Microbiology and Immunology, State University of New York at Buffalo, 14214, USA.
Infect Immun. 2004 Nov;72(11):6426-32. doi: 10.1128/IAI.72.11.6426-6432.2004.
Moraxella catarrhalis is a major cause of acute otitis media in young children and has also been implicated as an important cause of exacerbations in adults with underlying pulmonary disease. Due to the considerable level of antibiotic resistance and the high degree of carriage rates in young children, it is likely that the incidence of M. catarrhalis infections will continue to rise. M. catarrhalis is a strict human respiratory pathogen, and this bacterium uses both transferrin and lactoferrin receptors to fulfill the essential iron requirement for survival in vivo. However, these are the only described iron acquisition systems for this organism. In this report we have demonstrated that M. catarrhalis can also utilize hemin as a sole source of iron for growth. In addition, we have identified and characterized an outer membrane protein with homology (26 to 28% similarity) to other known hemin binding and uptake proteins in related gram-negative organisms (i.e., Bordetella and Yersinia spp.). This newly described M. catarrhalis protein, termed HumA, is capable of directly binding to hemin coupled to a solid-phase matrix. M. catarrhalis HumA expressed on the surface of an Escherichia coli hemA-deficient strain (K-12 EB53) is fully capable of complementing the defect and thus restoring the ability of this strain to grow in the presence of hemin. When M. catarrhalis is grown in the presence of hemin, HumA expression is clearly increased as shown by Western blotting with polyclonal antiserum developed against a HumA peptide. In addition, growth analyses revealed that a HumA-deficient mutant of M. catarrhalis (7169::humA) is restricted for growth in the presence of hemin as the sole iron source compared to the wild-type strain. We conclude that HumA is an essential component of a hemin uptake and utilization system previously undescribed for M. catarrhalis, thus providing another mechanism of iron acquisition that may facilitate persistent colonization of the mucosal surface.
卡他莫拉菌是幼儿急性中耳炎的主要病因，也被认为是患有基础肺部疾病的成人病情加重的重要原因。由于其抗生素耐药水平较高，且在幼儿中的携带率很高，卡他莫拉菌感染的发病率可能会持续上升。卡他莫拉菌是一种严格的人类呼吸道病原体，该细菌利用转铁蛋白和乳铁蛋白受体来满足其在体内生存所需的基本铁需求。然而，这些是该生物体仅有的已描述的铁获取系统。在本报告中，我们证明了卡他莫拉菌还可以利用血红素作为唯一的铁源进行生长。此外，我们鉴定并表征了一种外膜蛋白，它与相关革兰氏阴性菌（即博德特氏菌属和耶尔森氏菌属）中其他已知的血红素结合和摄取蛋白具有同源性（相似性为26%至28%）。这种新描述的卡他莫拉菌蛋白称为HumA，能够直接结合与固相基质偶联的血红素。在大肠杆菌血红素缺陷型菌株（K - 12 EB53）表面表达的卡他莫拉菌HumA完全能够弥补缺陷，从而恢复该菌株在血红素存在下生长的能力。当卡他莫拉菌在血红素存在下生长时，如用针对HumA肽产生的多克隆抗血清进行蛋白质印迹分析所示，HumA的表达明显增加。此外，生长分析表明，与野生型菌株相比，卡他莫拉菌HumA缺陷型突变体（7169::humA）在以血红素作为唯一铁源的情况下生长受限。我们得出结论，HumA是卡他莫拉菌先前未描述的血红素摄取和利用系统的重要组成部分，因此提供了另一种铁获取机制，这可能有助于在粘膜表面持续定植。
