Myeloperoxidase Selectively Binds and Selectively Kills Microbes

Myeloperoxidase Selectively Binds and Selectively Kills Microbes
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DOI:
10.1128/iai.00910-09
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发表时间:
2011-01-01
影响因子:
3.1
通讯作者:
Stephens, Jackson T., Jr.
Stephens, Jackson T., Jr.
中科院分区:
医学2区
文献类型:
--
作者:
Allen, Robert C.;Stephens, Jackson T., Jr.

文献摘要

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髓过氧化物酶(MPO)被报道选择性地与细菌结合。本研究提供了MPO选择性结合的直接证据,并测试了选择性结合与选择性杀伤的关系。比较了H2O2和OCl-的抑菌效果与MPO + H2O2的抑菌效果。通过将低MPO结合的产H2O2微生物——血链球菌(Streptococcus sanguinis)与高MPO结合的不含外源性H2O2的大肠杆菌、金黄色葡萄球菌或铜绿假单胞菌(Pseudomonas aeruginosa)、含和不含MPO以及含和不含红细胞(red blood cells [rbc])联合使用,研究了协同杀微生物作用。对大肠杆菌、铜绿假单胞菌、金黄色葡萄球菌、粪肠球菌、化脓性链球菌、无乳链球菌和绿绿链球菌等82种细菌,采用MPO MIC和最小杀菌浓度(MBC)测定MPO杀灭微生物的选择性。H2O2和OCl-都以亚杀微生物浓度破坏红细胞。纳米摩尔浓度的MPO将H2O2的杀微生物作用提高了1000倍。链球菌加MPO对所有测试的微生物产生了有效的协同杀微生物作用,而红细胞只引起效力的轻微下降,而红细胞没有损伤。MPO直接杀死产H(2)O(2)的产化脓链球菌,但对不产h2o2的粪肠杆菌无效。大肠杆菌、铜绿假单胞菌和金黄色葡萄球菌的MPO mic和MBCs显著低于粪肠杆菌。链球菌研究显示了更高的MIC/MBC结果,但这种测试需要溶解的马血补充培养基,因此无法将这些结果与其他微生物的结果进行有效比较。据报道,与大肠杆菌、铜绿假单胞菌和金黄色葡萄球菌的结合相比,粪肠杆菌的MPO结合弱,但与链球菌的结合强。选择性MPO结合导致选择性杀伤。
Myeloperoxidase (MPO) is reported to selectively bind to bacteria. The present study provides direct evidence of MPO binding selectivity and tests the relationship of selective binding to selective killing. The microbicidal effectiveness of H2O2 and of OCl- was compared to that of MPO plus H2O2. Synergistic microbicidal action was investigated by combining Streptococcus sanguinis, a H2O2-producing microbe showing low MPO binding, with high-MPO-binding Escherichia coli, Staphylococcus aureus, or Pseudomonas aeruginosa without exogenous H2O2, with and without MPO, and with and without erythrocytes (red blood cells [RBCs]). Selectivity of MPO microbicidal action was conventionally measured as the MPO MIC and minimal bactericidal concentration (MBC) for 82 bacteria including E. coli, P. aeruginosa, S. aureus, Enterococcus faecalis, Streptococcus pyogenes, Streptococcus agalactiae, and viridans streptococci. Both H2O2 and OCl- destroyed RBCs at submicrobicidal concentrations. Nanomolar concentrations of MPO increased H2O2 microbicidal action 1,000-fold. Streptococci plus MPO produced potent synergistic microbicidal action against all microbes tested, and RBCs caused only a small decrease in potency without erythrocyte damage. MPO directly killed H(2)O(2)producing S. pyogenes but was ineffective against non-H2O2-producing E. faecalis. The MPO MICs and MBCs for E. coli, P. aeruginosa, and S. aureus were significantly lower than those for E. faecalis. The streptococcal studies showed much higher MIC/MBC results, but such testing required lysed horse blood-supplemented medium, thus preventing valid comparison of these results to those for the other microbes. E. faecalis MPO binding is reportedly weak compared to binding of E. coli, P. aeruginosa, and S. aureus but strong compared to binding of streptococci. Selective MPO binding results in selective killing.