Distinct but Spatially Overlapping Intestinal Niches for Vancomycin-Resistant Enterococcus faecium and Carbapenem-Resistant Klebsiella pneumoniae.
Distinct but Spatially Overlapping Intestinal Niches for Vancomycin-Resistant Enterococcus faecium and Carbapenem-Resistant Klebsiella pneumoniae.
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DOI：
10.1371/journal.ppat.1005132
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发表时间：
2015-09
期刊：
影响因子：
6.7
通讯作者：
Pamer EG
中科院分区：
文献类型：
--
作者：
Caballero S;Carter R;Ke X;Sušac B;Leiner IM;Kim GJ;Miller L;Ling L;Manova K;Pamer EG
肠球菌和γ-变形菌中的抗生素耐药性是医疗机构中日益严重的问题。耐药细菌在肠道的密集定植促进了它们在患者之间的传播，也导致了血流和其他全身性感染。抗生素介导的肠道微生物群的破坏和随之而来的定植抗性的丧失是导致耐药性细菌持续存在和传播的关键因素。微生物群介导的定殖抗性的潜在机制仍然不完全确定，并且对于不同的耐药性细菌物种可能是不同的。目前尚不清楚肠球菌或γ-变形菌在肠道中扩增至高密度后是否赋予对竞争细菌物种的定殖抗性。在此，我们证明了万古霉素耐药屎肠球菌（VRE）在肠道的密集定植不会减少碳青霉烯类耐药肺炎克雷伯菌的体内生长。相反，K。肺炎并不损害VRE的肠道定植。相比之下，移植不同的粪便微生物群消除了VRE和K。从肠道感染肺炎荧光原位杂交结果表明，VRE和K。肺炎杆菌定位于结肠中的相同区域，但在结肠粘液层的刺激和侵入方面不同。VRE和K.尽管肺炎克雷伯氏菌在肠腔内占据相同的三维空间，但它们在肠中的独立生长和持久性表明它们存在于满足其特定体内代谢需要的不同小生境中。肠道定植先于医院病原体万古霉素耐药肠球菌（VRE）和碳青霉烯耐药肺炎克雷伯菌的播散性感染和菌血症的发展。尽管抗生素治疗使小鼠对VRE或K.对于肺炎，目前还不清楚这些微生物是否会在肠道中争夺空间和资源。我们的定量研究表明，无论是VRE或K。pneumoniae不受其他物种的影响，这表明它们占据了不同的生态位。使用荧光原位杂交，我们表明，这两种细菌确实占据不同的壁龛，但栖息在肠道内的相同区域。我们发现K。pneumoniae，而不是VRE，诱导粘液产生并侵入邻近结肠上皮细胞的粘液层，可能导致K.肺炎转移至肠系膜淋巴结。尽管VRE和K.在移植健康的微生物群后，肺炎链球菌可以从肠腔移位。我们的研究提供了VRE和K之间的相互作用的见解。与对方，与自己的主人。
Antibiotic resistance among enterococci and γ-proteobacteria is an increasing problem in healthcare settings. Dense colonization of the gut by antibiotic-resistant bacteria facilitates their spread between patients and also leads to bloodstream and other systemic infections. Antibiotic-mediated destruction of the intestinal microbiota and consequent loss of colonization resistance are critical factors leading to persistence and spread of antibiotic-resistant bacteria. The mechanisms underlying microbiota-mediated colonization resistance remain incompletely defined and are likely distinct for different antibiotic-resistant bacterial species. It is unclear whether enterococci or γ-proteobacteria, upon expanding to high density in the gut, confer colonization resistance against competing bacterial species. Herein, we demonstrate that dense intestinal colonization with vancomycin-resistant Enterococcus faecium (VRE) does not reduce in vivo growth of carbapenem-resistant Klebsiella pneumoniae. Reciprocally, K. pneumoniae does not impair intestinal colonization by VRE. In contrast, transplantation of a diverse fecal microbiota eliminates both VRE and K. pneumoniae from the gut. Fluorescence in situ hybridization demonstrates that VRE and K. pneumoniae localize to the same regions in the colon but differ with respect to stimulation and invasion of the colonic mucus layer. While VRE and K. pneumoniae occupy the same three-dimensional space within the gut lumen, their independent growth and persistence in the gut suggests that they reside in distinct niches that satisfy their specific in vivo metabolic needs. Intestinal colonization precedes the development of disseminated infections and bacteremia by the nosocomial pathogens vancomycin-resistant Enterococcus (VRE) and carbapenem-resistant Klebsiella pneumoniae. Although antibiotic treatment renders mice susceptible to dense colonization by VRE or K. pneumoniae, it is unclear whether these microbes compete for space and resources in the gut. Our quantitative studies demonstrate that the density of intestinal colonization by either VRE or K. pneumoniae is unaffected by the presence of the other species, suggesting that they occupy separate niches. Using fluorescence in situ hybridization, we show that both bacterial species indeed occupy distinct niches but inhabit the same regions within the intestine. We find that K. pneumoniae, but not VRE, induces mucus production and invades the mucus layer adjacent to colonic epithelial cells, potentially leading to increased K. pneumoniae translocation to mesenteric lymph nodes. Despite their high colonization levels, both VRE and K. pneumoniae can be displaced from the intestinal lumen following transplantation of a healthy microbiota. Our study provides insight into the interactions between VRE and K. pneumoniae with each other and with their host.