한빛사논문
- 조회187
Washington University School of Medicine in St. Louis
JooHee Choi a,m, Robert Thänert a,b,m, Kimberly A. Reske c, Katelin B. Nickel c, Margaret A. Olsen c, Tiffany Hink c, Anna Thänert a, Meghan A. Wallace b, Bin Wang a,b, Candice Cass c, Margaret H. Barlet c, Emily L. Struttmann c, Zainab Hassan Iqbal c, Steven R. Sax c, Victoria J. Fraser c, Arthur W. Baker d,e, Katherine R. Foy d,e, Brett Williams f, Ben Xu f, Pam Capocci-Tolomeo g,h, Ebbing Lautenbach h,i, Carey-Ann D. Burnham b,c,j,k, Erik R. Dubberke c, Gautam Dantas a,b,j,k,l, Jennie H. Kwon c on behalf of the CDC Prevention Epicenters Program
aThe Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA
bDepartment of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA
cDivision of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
dDivision of Infectious Diseases, Duke University School of Medicine, Durham, NC, USA
eDuke Center for Antimicrobial Stewardship and Infection Prevention, Durham, NC, USA
fDivision of Infectious Diseases, Department of Internal Medicine, Rush Medical College, Chicago, IL, USA
gDepartment of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
hCenter for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
iDivision of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
jDepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
kDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
lDepartment of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA
mThese authors contributed equally.
Corresponding authors: Erik R. Dubberke, Gautam Dantas, Jennie H. Kwon
Abstract
Background: Urinary tract infections (UTI) affect approximately 250 million people annually worldwide. Patients often experience a cycle of antimicrobial treatment and recurrent UTI (rUTI) that is thought to be facilitated by a gut reservoir of uropathogenic Escherichia coli (UPEC).
Methods: 125 patients with UTI caused by an antibiotic-resistant organism (ARO) were enrolled from July 2016 to May 2019 in a longitudinal, multi-center cohort study. Multivariate statistical models were used to assess the relationship between uropathogen colonization and recurrent UTI (rUTI), controlling for clinical characteristics. 644 stool samples and 895 UPEC isolates were interrogated for taxonomic composition, antimicrobial resistance genes, and phenotypic resistance. Cohort UTI gut microbiome profiles were compared against published healthy and UTI reference microbiomes, as well as assessed within-cohort for timepoint- and recurrence-specific differences.
Findings: Risk of rUTI was not independently associated with clinical characteristics. The UTI gut microbiome was distinct from healthy reference microbiomes in both taxonomic composition and antimicrobial resistance gene (ARG) burden, with 11 differentially abundant taxa at the genus level. rUTI and non-rUTI gut microbiomes in the cohort did not generally differ, but gut microbiomes from urinary tract colonized patients were elevated in E. coli abundance 7-14 days post-antimicrobial treatment. Corresponding UPEC gut isolates from urinary tract colonizing lineages showed elevated phenotypic resistance against 11 of 23 tested drugs compared to non-colonizing lineages.
Interpretation: The gut microbiome is implicated in UPEC urinary tract colonization during rUTI, serving as an ARG-enriched reservoir for UPEC. UPEC can asymptomatically colonize the gut and urinary tract, and post-antimicrobial blooms of gut E. coli among urinary tract colonized patients suggest that cross-habitat migration of UPEC is an important mechanism of rUTI. Thus, treatment duration and UPEC populations in both the urinary and gastrointestinal tract should be considered in treating rUTI and developing novel therapeutics.
Funding: This work was supported in part by awards from the U.S. Centers for Disease Control and Prevention Epicenter Prevention Program (grant U54CK000482; principal investigator, V.J.F.); to J.H.K. from the Longer Life Foundation (an RGA/Washington University partnership), the National Center for Advancing Translational Sciences (grants KL2TR002346 and UL1TR002345), and the National Institute of Allergy and Infectious Diseases (NIAID) (grant K23A1137321) of the National Institutes of Health (NIH); and to G.D. from NIAID (grant R01AI123394) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant R01HD092414) of NIH. R.T.'s research was funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation; grant 402733540). REDCap is Supported by Clinical and Translational Science Award (CTSA) Grant UL1 TR002345 and Siteman Comprehensive Cancer Center and NCI Cancer Center Support Grant P30 CA091842. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
논문정보
- Research article
- 2024년 05월 (BRIC 등록일 2024-06-04)
- 국외 연구진
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