Episymbiotic Saccharibacteria TM7x modulates the susceptibility of its host bacteria to phage infection and promotes their coexistence

作者全名：Zhong, Qiu; Liao, Binyou; Liu, Jiazhen; Shen, Wei; Wang, Jing; Wei, Leilei; Ma, Yansong; Dong, Pu-Ting; Bor, Batbileg; McLean, Jeffrey S.; Chang, Yunjie; Shi, Wenyuan; Cen, Lujia; Wu, Miaomiao; Liul, Jun; Li, Yan; He, Xuesong; Le, Shuai

作者地址：[Zhong, Qiu; Liu, Jiazhen; Wang, Jing; Le, Shuai] Chongqing Army Med Univ, Key Lab Microbial Engn Educ Comm Chongqing, Coll Basic Med Sci, Dept Microbiol, Chongqing 400038, Peoples R China; [Liao, Binyou; Wu, Miaomiao; Li, Yan] Sichuan Univ, West China Hosp Stomatol, Natl Ctr Stomatol, Natl Clin Res Ctr Oral Dis,State Key Lab Oral Dis, Chengdu 610041, Sichuan, Peoples R China; [Shen, Wei] Chongqing Med Univ, Affiliated Hosp 2, Dept Infect Dis,Key Lab Mol Biol Infect Dis, Chongqing 401336, Peoples R China; [Wei, Leilei] Army Med Univ, Daping Hosp, Dept Lab Med, Chongqing 400038, Peoples R China; [Ma, Yansong] Capital Med Univ, Dept Orthodont, Beijing 100050, Peoples R China; [Dong, Pu-Ting; Bor, Batbileg; Shi, Wenyuan; Cen, Lujia; He, Xuesong] Amer Dent Assoc Forsyth Inst, Dept Microbiol, Cambridge, MA 02142 USA; [Bor, Batbileg; He, Xuesong] Harvard Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA; [McLean, Jeffrey S.] Univ Washington, Dept Periodont, Seattle, WA 98119 USA; [McLean, Jeffrey S.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA; [Chang, Yunjie] Zhejiang Univ, Sch Med, Dept Cell Biol, Hangzhou 310058, Zhejiang, Peoples R China; [Chang, Yunjie] Zhejiang Univ, Sir Run Run Shaw, Sch Med, Dept Infect Dis, Hangzhou 310058, Zhejiang, Peoples R China; [Liul, Jun] Yale Sch Med, Dept Microbial Pathogenesis, New Haven, CT 06536 USA

通信作者：Le, S (通讯作者)，Chongqing Army Med Univ, Key Lab Microbial Engn Educ Comm Chongqing, Coll Basic Med Sci, Dept Microbiol, Chongqing 400038, Peoples R China.; Li, Y (通讯作者)，Sichuan Univ, West China Hosp Stomatol, Natl Ctr Stomatol, Natl Clin Res Ctr Oral Dis,State Key Lab Oral Dis, Chengdu 610041, Sichuan, Peoples R China.; He, XS (通讯作者)，Amer Dent Assoc Forsyth Inst, Dept Microbiol, Cambridge, MA 02142 USA.; He, XS (通讯作者)，Harvard Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.

来源：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

ESI学科分类：Multidisciplinary

WOS号：WOS:001209030400001

JCR分区：Q1

影响因子：9.4

年份：2024

卷号：121

期号：16

开始页：　

结束页：　

文献类型：Article

关键词：TM7x |; Saccharibacteria; phage resistance; bacteria-phage interaction |; episymbiosis

摘要：Bacteriophages (phages) play critical roles in modulating microbial ecology. Within the human microbiome, the factors influencing the long - term coexistence of phages and bacteria remain poorly investigated. Saccharibacteria (formerly TM7) are ubiquitous members of the human oral microbiome. These ultrasmall bacteria form episymbiotic relationships with their host bacteria and impact their physiology. Here, we showed that during surface- associated growth, a human oral Saccharibacteria isolate (named TM7x) protects its host bacterium, a Schaalia odontolytica strain (named XH001) against lytic phage LC001 predation. RNA- Sequencing analysis identified in XH001 a gene cluster with predicted functions involved in the biogenesis of cell wall polysaccharides (CWP), whose expression is significantly down- regulated when forming a symbiosis with TM7x. Through genetic work, we experimentally demonstrated the impact of the expression of this CWP gene cluster on bacterial-phage interaction by affecting phage binding. In vitro coevolution experiments further showed that the heterogeneous populations of TM7x- associated and TM7x-free XH001, which display differential susceptibility to LC001 predation, promote bacteria and phage coexistence. Our study highlights the tripartite interaction between the bacterium, episymbiont, and phage. More importantly, we present a mechanism, i.e., episymbiont- mediated modulation of gene expression in host bacteria, which impacts their susceptibility to phage predation and contributes to the formation of "source- sink" dynamics between phage and bacteria in biofilm, promoting their long - term coexistence within the human microbiome.

基金机构：National Institute of Dental and Craniofacial Research of the NIH [1R01DE023810, R01DE030943, 1R01DE031274]; National Natural Science Foundation of China [31870167, 81991502]; National Institute of General Medical Sciences [R01GM124378, R01GM110243]; National Institute of Allergy and Infectious Diseases [R01AI152421]; NIH [1S10OD023603-01A1]

基金资助正文：Research in this publication was supported by the National Institute of Dental and Craniofacial Research of the NIH under awards 1R01DE023810 (to X.H., J.S.M., and W. Shi) , R01DE030943 (to X.H.) , and 1R01DE031274 (to B.B.) . The research was also partly supported by the National Natural Science Foundation of China grants: 31870167 (to S.L.) and 81991502 (to Y.L.) . We thank Meng Shao for preparing cryo-ET samples with cryo-FIB at the Liu laboratory at Yale; Y.C. and Jun Liu. were supported by grants R01GM124378 and R01GM110243 from National Institute of General Medical Sciences and R01AI152421 from the National Institute of Allergy and Infectious Diseases; cryo-ET data were collected at the Yale cryo-EM resources and funded in part by the NIH grant 1S10OD023603-01A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.