PerR-regulated manganese ion uptake contributes to oxidative stress defense in an oral streptococcus----中国科学院微生物研究所

科研成果

论文题目:	PerR-regulated manganese ion uptake contributes to oxidative stress defense in an oral streptococcus
作者:	Wang Xinhui, Tong Huichun*, Dong Xiuzhu
联系作者:	Tong Huichun*
刊物名称:	Appl Environ Microbiol
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年份:	2014
影响因子:	4.406
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摘要:	Metal homeostasis plays a critical role in anti-oxidative stress. Streptococcus oligofermentans, an oral commensal facultative anaerobe lacking catalase activity, produces and tolerates abundant H2O2, whereas Dpr, a Fe2+-chelating protein, dependent H2O2 protection does not confer such high tolerance. Here, we report that inactivation of perR, a peroxide-responsive repressor that regulates zinc and iron homeostasis in Gram-positive bacteria, increased 32-fold survival of H2O2 pulsed S. oligofermentans and elevated the cellular manganese for 4.5-fold. perR complementation recovered the wild type phenotype. When growing in 0.1-0.25 mM MnCl2, S. oligofermentans increased 2.5-23-fold survival after H2O2 stress, and even higher survival was found for the perR mutant, indicating that PerR is involved in Mn2+-mediated H2O2 resistance in S. oligofermentans. Mutation of mntA could not be obtained in BHI broth (containing approximately 0.4 muM Mn2+) unless supplemented with >/=2.5 muM MnCl2, and caused 82-95% reduced cellular Mn2+ level; while mntABC overexpression increased cellular Mn2+ for 2.1-4.5-fold. Thus MntABC was identified as a high-affinity Mn2+ transporter in S. oligofermentans. mntA mutation reduced 5.7-fold survival of H2O2 pulsed S. oligofermentans, while mntABC overexpression enhanced 12-fold H2O2-challengedsurvival, indicating that MntABC-mediated Mn2+ uptake is pivotal to anti-oxidative stress in S. oligofermentans. perR mutation or H2O2 pulsing upregulated mntABC, while H2O2-induced upregulation diminished in the perR mutant. This suggests that perR represses mntABC expression, but H2O2 can release the suppression. In conclusion, this work demonstrates that PerR regulates manganese homeostasis in S. oligofermentans, which is critical to H2O2 stress defenses and may be distributed across all catalase-lacking oral streptococci.