肠道是药物抗性细菌的重要定植场所,这些抗药细菌的存在对人类生命健康存在很大威胁。近日,来自美国的研究人员在国际学术期刊plos pathogens上发表了一项最新研究进展,他们利用小鼠进行研究发现两种最常见的抗药细菌在肠道中占据着相同位置,同时将健康的肠道菌群通过粪便移植的方式转移到小鼠模型中可以清除抗药细菌。
研究人员对肠道环境中携带万古霉素抗性的Enterococcus faecium(VRE)和携带多种药物抗性的Klebsiella pneumoniae之间的相互作用进行了研究。有数据表明,在美国有大约10%需要住院治疗的严重病原体感染是由这两种细菌造成。这两种细菌都可以在肠道中定植下来并向其他部位传播,引起自身或他人发生局部感染或全身感染。
研究人员首先提出一个问题:是否VRE或K. pneumoniae中的一种占据小肠环境之后就会对另外一种细菌的定植产生抵抗。在利用小鼠模型进行研究之后发现这两种细菌能够同时占据小肠中的相同位置,并且在定植过程中两者之间不会形成竞争也不会产生协同作用。虽然这两种细菌可以和平共处,但研究人员发现它们驻留在不同的"niches"之中,以满足各自的代谢需求。
目前大家已经了解将健康小鼠的粪便移植到细菌定植的小鼠肠道可以清除VRE,而对于人类来说,利用健康供体进行粪便移植可以治疗一些受到肠道特定病原菌感染的病人。为了证明粪便移植是否也能够清除VRE和K. pneumoniae ,研究人员首先将这两种病原菌共同定植到小鼠肠道,随后进行了连续三天的健康粪便菌群移植。结果发现在进行了一天的移植之后,K. pneumoniae就出现下降,而七天之后所有的小鼠粪便中都检测不到K. pneumoniae的存在,而VRE在60%的小鼠中得到清除,在剩余40%的小鼠中减少了一千倍。
总的来说,这项研究发现VRE和K. pneumoniae这两种抗药病原菌可以在小鼠肠道中共同存在,并且利用粪便移植的方法可以将这两种病原菌进行清除,这对于深入探究肠道细菌的关系具有重要意义。
DOI: 10.1371/journal.ppat.1005132
Distinct but Spatially Overlapping Intestinal Niches for Vancomycin-Resistant Enterococcus faecium and Carbapenem-Resistant Klebsiella pneumoniae
Silvia Caballero, Rebecca Carter, Xu Ke, Bo?e Su?ac, Ingrid M. Leiner, Grace J. Kim, Liza Miller, Lilan Ling, Katia Manova, Eric G. Pamer
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 mechanis 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.