Institut Pasteur, Département de Biologie Cellulaire et Infection, Unité des Interactions Bactéries-Cellules, Paris, France.
J Infect Dis. 2011 Sep 1;204(5):731-40. doi: 10.1093/infdis/jir396.
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, β-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.
微生物病原体已经进化出多种机制来克服免疫反应并成功感染宿主。在这里，我们研究了李斯特菌如何通过肽聚糖（PGN）修饰来逃避免疫检测。通过分析李斯特菌的肽聚糖，我们检测到了 O-乙酰化的胞壁酸残基。我们在李斯特菌基因组序列中鉴定了一个 O-乙酰转移酶基因 oatA。比较亲本和同源 oatA 突变株的 PGN 表明，O-乙酰转移酶 OatA 对李斯特菌 PGN 进行 O-乙酰化。我们还发现，PGN 的 O-乙酰化赋予了细菌对不同类型的针对细胞壁的抗菌化合物的抗性，例如溶菌酶、β-内酰胺类抗生素和细菌素，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 突变体在静脉内或口服接种的小鼠中的毒力受到严重影响。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中细菌存活方面发挥着重要作用。
