Sword and shield:: Linked group B streptococcal β-hemolysin/cytolysin and carotenoid pigment function to subvert host phagocyte defense

被引:168
作者
Liu, GY
Doran, KS
Lawrence, T
Turkson, N
Puliti, M
Tissi, L
Nizet, V [1 ]
机构
[1] Univ Calif San Diego, Scripps Inst Oceanog, Dept Pediat, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Scripps Inst Oceanog, Dept Pharmacol, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Scripps Inst Oceanog, Ctr Marine Biotechnol & Biomed, La Jolla, CA 92093 USA
[4] Univ Perugia, Dept Expt Med & Biochem Sci, Microbiol Sect, I-06122 Perugia, Italy
基金
英国惠康基金;
关键词
D O I
10.1073/pnas.0406143101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Group B Streptococcus (GBS) is a major cause of pneumonia, bacteremia, and meningitis in neonates and has been found to persist inside host phagocytic cells. The pore-forming GBS beta-hemolysin/ cytolysin (betaH/C) encoded by cylE is an important virulence factor as demonstrated in several in vivo models. Interestingly, cylE deletion results not only in the loss of betaH/C activity, but also in the loss of a carotenoid pigment of unknown function. in this study, we sought to define the mechanism(s) by which cylE may contribute to GBS phagocyte resistance and increased virulence potential. We found that cylE-deficient GBS was more readily cleared from a mouse's bloodstream, human whole blood, and isolated macrophage and neutrophil cultures. Survival was linked to the ability of betaH/C to induce cytolysis and apoptosis of the phagocytes. At a lower bacterial inoculum, cylE also contributed to enhanced survival within phagocytes that was attributed to the ability of carotenoid to shield GBS from oxidative damage. In oxidant killing assays, cylE mutants were shown to be more susceptible to hydrogen peroxide, hypochlorite, superoxide, and singlet oxygen. Together, these data suggest a mechanism by which the linked cylE-encoded phenotypes, betaH/C (sword) and carotenoid (shield), act in partnership to thwart the immune phagocytic defenses.
引用
收藏
页码:14491 / 14496
页数:6
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