Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Weill Cornell Medical College, New York, NY, USA.
Nature. 2019 Aug;572(7771):665-669. doi: 10.1038/s41586-019-1501-z. Epub 2019 Aug 21.
Intestinal commensal bacteria can inhibit dense colonization of the gut by vancomycin-resistant Enterococcus faecium (VRE), a leading cause of hospital-acquired infections. A four-strained consortium of commensal bacteria that contains Blautia producta BP can reverse antibiotic-induced susceptibility to VRE infection. Here we show that BP reduces growth of VRE by secreting a lantibiotic that is similar to the nisin-A produced by Lactococcus lactis. Although the growth of VRE is inhibited by BP and L. lactis in vitro, only BP colonizes the colon and reduces VRE density in vivo. In comparison to nisin-A, the BP lantibiotic has reduced activity against intestinal commensal bacteria. In patients at high risk of VRE infection, high abundance of the lantibiotic gene is associated with reduced density of E. faecium. In germ-free mice transplanted with patient-derived faeces, resistance to VRE colonization correlates with abundance of the lantibiotic gene. Lantibiotic-producing commensal strains of the gastrointestinal tract reduce colonization by VRE and represent potential probiotic agents to re-establish resistance to VRE.
肠道共生细菌可以抑制万古霉素耐药粪肠球菌(VRE)的密集定植,而 VRE 是医院获得性感染的主要原因。含有布氏瘤胃球菌 BP 的四种共生细菌组成的联合体可以逆转抗生素诱导的 VRE 感染易感性。在这里,我们发现 BP 通过分泌类似于乳球菌 lactis 产生的乳链菌肽的类细菌素来抑制 VRE 的生长。尽管 BP 和 L. lactis 在体外抑制 VRE 的生长,但只有 BP 在体内定植结肠并降低 VRE 的密度。与乳链菌肽相比,BP 类细菌素对肠道共生细菌的活性降低。在 VRE 感染风险高的患者中,类细菌素基因的高丰度与粪肠球菌密度降低相关。在移植了患者来源粪便的无菌小鼠中,对 VRE 定植的抗性与类细菌素基因的丰度相关。胃肠道中产类细菌素的共生菌株可减少 VRE 的定植,代表了重新建立对 VRE 抗性的潜在益生菌制剂。