Human commensals producing a novel antibiotic impair pathogen colonization
Human commensals producing a novel antibiotic impair pathogen colonization
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DOI：
10.1038/nature18634
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发表时间：
2016-07-28
期刊：
影响因子：
64.8
通讯作者：
Krismer, Bernhard
中科院分区：
文献类型：
--
作者：
Zipperer, Alexander;Konnerth, Martin C.;Krismer, Bernhard
绝大多数全身性细菌感染是由兼性的，通常是耐抗生素的，病原体定植在人体表面引起的。金黄色葡萄球菌的鼻腔携带易导致侵袭性感染，但允许或干扰病原体定植的机制在很大程度上尚不清楚。众所周知，土壤微生物通过生产抗生素来竞争，但很少有关于人类微生物群的此类过程的报道。我们发现，鼻卢顿葡萄球菌菌株产生卢顿蛋白，这是一种新型含噻唑烷的环肽抗生素，可以阻止金黄色葡萄球菌的定植，也是一种罕见的从人类相关细菌中合成的非核糖体生物活性化合物。Lugdunin对主要病原体具有杀菌作用，在动物模型中有效，并且不易引起金黄色葡萄球菌的耐药性。值得注意的是，lugdunensis的人类鼻腔定植与金黄色葡萄球菌携带率显著降低相关，这表明lugdunin或产生lugdunin的共生菌可能对预防葡萄球菌感染有价值。此外，人类微生物群应被视为新抗生素的来源。
The vast majority of systemic bacterial infections are caused by facultative, often antibiotic-resistant, pathogens colonizing human body surfaces. Nasal carriage of Staphylococcus aureus predisposes to invasive infection, but the mechanisms that permit or interfere with pathogen colonization are largely unknown. Whereas soil microbes are known to compete by production of antibiotics, such processes have rarely been reported for human microbiota. We show that nasal Staphylococcus lugdunensis strains produce lugdunin, a novel thiazolidine-containing cyclic peptide antibiotic that prohibits colonization by S. aureus, and a rare example of a non-ribosomally synthesized bioactive compound from human-associated bacteria. Lugdunin is bactericidal against major pathogens, effective in animal models, and not prone to causing development of resistance in S. aureus. Notably, human nasal colonization by S. lugdunensis was associated with a significantly reduced S. aureus carriage rate, suggesting that lugdunin or lugdunin-producing commensal bacteria could be valuable for preventing staphylococcal infections. Moreover, human microbiota should be considered as a source for new antibiotics.