Alteri Christopher J, Himpsl Stephanie D, Mobley Harry L T
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
PLoS Pathog. 2015 Jan 8;11(1):e1004601. doi: 10.1371/journal.ppat.1004601. eCollection 2015 Jan.
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.
人类泌尿生殖道是多微生物感染常见的解剖学生态位，也是菌血症和败血症发生的主要部位。大多数非复杂性社区获得性尿路感染（UTI）由大肠杆菌引起，而另一种细菌奇异变形杆菌则更常与复杂性UTI相关。在此，我们报告致病性大肠杆菌和奇异变形杆菌尽管定殖并占据相同的宿主环境，但在体内对特定中心途径有不同的需求。利用特定中心代谢酶的突变体，我们确定缺乏pgi、tpiA、pfkA或pykA的糖酵解突变体在体内对奇异变形杆菌均有适应性缺陷，但在UTI期间不影响大肠杆菌的定殖。同样，氧化戊糖磷酸途径仅在体内对奇异变形杆菌是必需的。相反，糖异生仅对大肠杆菌在体内的适应性是必需的。在实验性UTI期间，对于sdhB、fumC和frdA中的三羧酸循环突变体，也观察到大肠杆菌和奇异变形杆菌在中心途径利用上的显著差异。这些病原体在体内的不同需求表明，大肠杆菌和奇异变形杆菌在宿主泌尿道营养生态位内并非直接竞争者。支持这一点的是，我们发现大肠杆菌和奇异变形杆菌野生型菌株的共感染增强了UTI期间两种病原体的细菌定殖和持续存在。我们的结果表明，中心碳代谢的互补利用促进了多微生物疾病，并表明体内的微生物活动改变了宿主泌尿道营养生态位。
