Department of Infectious Diseases, University of Georgia, Athens, Georgia, USA.
J Bacteriol. 2014 Jan;196(1):107-20. doi: 10.1128/JB.00298-13. Epub 2013 Oct 18.
The major phospholipid constituents of Moraxella catarrhalis membranes are phosphatidylglycerol, phosphatidylethanolamine, and cardiolipin (CL). However, very little is known regarding the synthesis and function of these phospholipids in M. catarrhalis. In this study, we discovered that M. catarrhalis expresses a cardiolipin synthase (CLS), termed MclS, that is responsible for the synthesis of CL within the bacterium. The nucleotide sequence of mclS is highly conserved among M. catarrhalis isolates and is predicted to encode a protein with significant amino acid similarity to the recently characterized YmdC/ClsC protein of Escherichia coli. Isogenic mclS mutant strains were generated in M. catarrhalis isolates O35E, O12E, and McGHS1 and contained no observable levels of CL. Site-directed mutagenesis of a highly conserved HKD motif of MclS also resulted in a CL-deficient strain. Moraxella catarrhalis, which depends on adherence to epithelial cells for colonization of the human host, displays significantly reduced levels of adherence to HEp-2 and A549 cell lines in the mclS mutant strains compared to wild-type bacteria. The reduction in adherence appears to be attributed to the absence of CL. These findings mark the first instance in which a CLS has been related to a virulence-associated trait.
粘膜炎莫拉氏菌膜的主要磷脂成分是磷脂酰甘油、磷脂酰乙醇胺和心磷脂（CL）。然而，对于粘膜炎莫拉氏菌中这些磷脂的合成和功能，我们知之甚少。在这项研究中，我们发现粘膜炎莫拉氏菌表达一种心磷脂合酶（CLS），称为 MclS，它负责细菌中心磷脂的合成。mclS 的核苷酸序列在粘膜炎莫拉氏菌分离株中高度保守，预测编码的蛋白与最近表征的大肠杆菌 YmdC/ClsC 蛋白具有显著的氨基酸相似性。在粘膜炎莫拉氏菌分离株 O35E、O12E 和 McGHS1 中生成了同源 mclS 突变株，它们不含有可观察到的 CL。MclS 的高度保守的 HKD 基序的定点突变也导致 CL 缺陷株的产生。粘膜炎莫拉氏菌依赖于对上皮细胞的黏附来定植人类宿主，与野生型细菌相比，在 mclS 突变株中，其对 HEp-2 和 A549 细胞系的黏附水平显著降低。这种黏附的减少似乎归因于 CL 的缺失。这些发现标志着首次将 CLS 与与毒力相关的特征联系起来。
