Global and local selection acting on the pathogen Stenotrophomonas maltophilia in the human lung

被引:40
作者
Chung, Hattie [1 ]
Lieberman, Tami D. [1 ]
Vargas, Sara O. [2 ]
Flett, Kelly B. [3 ]
McAdam, Alexander J. [4 ]
Priebe, Gregory P. [3 ,5 ]
Kishony, Roy [1 ,6 ,7 ]
机构
[1] Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA
[2] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA
[3] Boston Childrens Hosp, Div Infect Dis, Dept Med, Boston, MA 02115 USA
[4] Boston Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA
[5] Boston Childrens Hosp, Div Crit Care Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA
[6] Technion Israel Inst Technol, Fac Biol, IL-32000 Haifa, Israel
[7] Technion Israel Inst Technol, Fac Comp Sci, IL-32000 Haifa, Israel
基金
欧洲研究理事会;
关键词
HUMAN GUT MICROBIOME; CYSTIC-FIBROSIS; PSEUDOMONAS-AERUGINOSA; RESISTANCE; BACTERIA;
D O I
10.1038/ncomms14078
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Bacterial populations diversify during infection into distinct subpopulations that coexist within the human body. Yet, it is unknown to what extent subpopulations adapt to location-specific selective pressures as they migrate and evolve across space. Here we identify bacterial genes under local and global selection by testing for spatial co-occurrence of adaptive mutations. We sequence 552 genomes of the pathogen Stenotrophomonas maltophilia across 23 sites of the lungs from a patient with cystic fibrosis. We show that although genetically close isolates colocalize in space, distant lineages with distinct phenotypes separated by adaptive mutations spread throughout the lung, suggesting global selective pressures. Yet, for one gene (a distant homologue of the merC gene implicated in metal resistance), mutations arising independently in two lineages colocalize in space, providing evidence for location-specific selection. Our work presents a general framework for understanding how selection acts upon a pathogen that colonizes and evolves across the complex environment of the human body.
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页数:7
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