OatA, a Peptidoglycan O-Acetyltransferase Involved in Listeria monocytogenes Immune Escape, Is Critical for Virulence
OatA, a Peptidoglycan O-Acetyltransferase Involved in Listeria monocytogenes Immune Escape, Is Critical for Virulence
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DOI：
10.1093/infdis/jir396
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发表时间：
2011-09-01
影响因子：
6.4
通讯作者：
Dussurget, Olivier
中科院分区：
文献类型：
--
作者：
Aubry, Camille;Goulard, Celine;Dussurget, Olivier
微生物病原体已经进化出克服免疫反应并成功感染宿主的机制。在这里，我们研究了单核细胞增生李斯特菌如何通过肽聚糖（PGN）修饰逃避免疫检测。通过分析单核增生乳杆菌的多肽，我们检测到o -乙酰化的乳杆菌酸残基。我们在单核增生乳杆菌的基因组序列中鉴定了一个o -乙酰转移酶基因oatA。亲本和等基因oatA突变株的PGN比较表明，o -乙酰基转移酶oatA能使李斯特菌PGN o -乙酰化。我们还发现，PGN的o -乙酰化对针对细菌细胞壁的不同类型的抗菌化合物（如溶菌酶、β -内酰胺抗生素和细菌素）具有耐药性，并且o -乙酰化是李斯特菌在巨噬细胞中生长所必需的。此外，oatA突变体的毒力在小鼠静脉或口服接种后会受到显著影响。此外，oatA突变体在体内诱导了促炎细胞因子和趋化因子的早期分泌。这些结果表明OatA在限制先天免疫反应和促进感染宿主细菌存活方面具有重要作用。
Microbial pathogens have evolved mechanisms to overcome immune responses and successfully infect their host. Here, we studied how Listeria monocytogenes evades immune detection by peptidoglycan (PGN) modification. By analyzing L. monocytogenes muropeptides, we detected O-acetylated muramic acid residues. We identified an O-acetyltransferase gene, oatA, in the L. monocytogenes genome sequence. Comparison of PGN from parental and isogenic oatA mutant strains showed that the O-acetyltransferase OatA O-acetylates Listeria PGN. We also found that PGN O-acetylation confers resistance to different types of antimicrobial compounds targeting bacterial cell wall such as lysozyme, beta-lactam antibiotics, and bacteriocins and that O-acetylation is required for Listeria growth in macrophages. Moreover, oatA mutant virulence is drastically affected in mice following intravenous or oral inoculation. In addition, the oatA mutant induced early secretion of proinflammatory cytokines and chemokines in vivo. These results suggest an important role for OatA in limiting innate immune responses and promoting bacterial survival in the infected host.