Staphylococcus aureus strains lacking D-alanine modifications of teichoic acids are highly susceptible to human neutrophil killing and are virulence attenuated in mice
Staphylococcus aureus strains lacking D-alanine modifications of teichoic acids are highly susceptible to human neutrophil killing and are virulence attenuated in mice
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DOI：
10.1086/341454
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发表时间：
2002-07-15
影响因子：
6.4
通讯作者：
Peschel, A
中科院分区：
文献类型：
--
作者：
Collins, LV;Kristian, SA;Peschel, A
金黄色葡萄球菌对α -防御素具有耐药性，α -防御素是一种抗菌肽，在人类嗜中性粒细胞的不依赖氧杀伤中起重要作用。dlt操纵子介导d -丙氨酸结合到葡萄球菌细胞包膜的壁酸中，是防御素抗性的决定因素。利用金黄色葡萄球菌野生型（WT）和Dlt（-）细菌，分析氧依赖型和非依赖型抗菌吞噬细胞成分的相对贡献。即使在没有功能性呼吸爆发的情况下，Dlt（-）菌株也能被人类中性粒细胞有效地杀死，而当呼吸爆发受到抑制时，WT生物体的杀伤能力大大降低。人类单核细胞不产生防御素，以相似的效率灭活了WT和Dlt（-）细菌。此外，与感染WT菌株的小鼠相比，注射Dlt（-）菌株的小鼠脓毒症和脓毒性关节炎的发生率显著降低，肾脏细菌数量也减少。
Staphylococcus aureus is resistant to alpha-defensins, antimicrobial peptides that play an important role in oxygen-independent killing of human neutrophils. The dlt operon mediates D-alanine incorporation into teichoic acids in the staphylococcal cell envelope and is a determinant of defensin resistance. By using S. aureus wild-type (WT) and Dlt(-) bacteria, the relative contributions of oxygen-dependent and -independent antimicrobial phagocyte components were analyzed. The Dlt(-) strain was efficiently killed by human neutrophils even in the absence of a functional respiratory burst, whereas the killing of the WT organism was strongly diminished when the respiratory burst was inhibited. Human monocytes, which do not produce defensins, inactivated the WT and Dlt(-) bacteria with similar efficiencies. In addition, mice injected with the Dlt(-) strain had significantly lower rates of sepsis and septic arthritis and fewer bacteria in the kidneys, compared with mice infected with the WT strain.