Preferential Use of Central Metabolism In Vivo Reveals a Nutritional Basis for Polymicrobial Infection

PLoS Pathogens

Harry L. T. Mobley¹  Stephanie D. Himpsl¹  Christopher J. Alteri¹ 

[1] Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America

关键词: Proteus mirabilis;    Urinary tract infections;    Bacterial pathogens;    Escherichia coli infections;    Bladder;    Renal system;    Kidneys;    Glycolysis;   

DOI  :  10.1371/journal.ppat.1004601

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The human genitourinary tract is a common anatomical niche for polymicrobial infection and a leading site for the development of bacteremia and sepsis. Most uncomplicated, community-acquired urinary tract infections (UTI) are caused by Escherichia coli, while another bacterium, Proteus mirabilis, is more often associated with complicated UTI. Here, we report that uropathogenic E. coli and P. mirabilis have divergent requirements for specific central pathways in vivo despite colonizing and occupying the same host environment. Using mutants of specific central metabolism enzymes, we determined glycolysis mutants lacking pgi, tpiA, pfkA, or pykA all have fitness defects in vivo for P. mirabilis but do not affect colonization of E. coli during UTI. Similarly, the oxidative pentose phosphate pathway is required only for P. mirabilis in vivo. In contrast, gluconeogenesis is required only for E. coli fitness in vivo. The remarkable difference in central pathway utilization between E. coli and P. mirabilis during experimental UTI was also observed for TCA cycle mutants in sdhB, fumC, and frdA. The distinct in vivo requirements between these pathogens suggest E. coli and P. mirabilis are not direct competitors within host urinary tract nutritional niche. In support of this, we found that co-infection with E. coli and P. mirabilis wild-type strains enhanced bacterial colonization and persistence of both pathogens during UTI. Our results reveal that complementary utilization of central carbon metabolism facilitates polymicrobial disease and suggests microbial activity in vivo alters the host urinary tract nutritional niche.

【 授权许可】

CC BY