A new Escherichia coli strain called ST131-H30 ? unknown prior to 2000 ? is now the single most common cause of E. coli infections such as urinary tract infections, particularly those associated with resistance to first- line antibiotics. Veterans are especially vulnerable to ST131-H30, which causes 25-30% of all their E. coli infections, and 70-75% of those involving fluoroquinolone (e.g., ciprofloxacin) resistance. Gut colonization is an important upstream step in ST131-H30 infections, and therefore is a key part of the ST131-H30 epidemic. We have found that, in veterans and their household members, gut colonization with fluoroquinolone-resistant E. coli (12-13% overall) is quite prolonged (possibly years), is significantly longer for ST131-H30 than other resistant E. coli, and is attributable more to strain persistence than frequent transmission. This suggests the possibility of reducing gut colonization with ST131-H30 by identifying modifiable risk factors, host immune factors, bacterial traits, and characteristics of the gut microbiota that correlate with prolonged H30 colonization and loss of colonization, to inform the development of appropriate interventions. Accordingly, we propose to augment our current longitudinal fecal surveillance of H30-colonized veterans and household members by: identifying epidemiological risk factors for presence and loss of H30 colonization identifying humoral and cell-mediated immune correlates of presence and loss of H30 colonization identifying genomic differences between initial vs. final, and shorter vs. longer-persisting, fecal ST131- H30 isolates identifying shifts in the gut microbiota (i.e., bacterial community and E. coli population) that correspond with presence and loss of H30 colonization. The results of these studies can be expected to provide essential information needed for the design of interventions (e.g., risk factor modification, vaccines, anti-colonization drugs, and pre- or probiotics) to reduce gut colonization with the ST131-H30 strains that cause infections in veterans. Such interventions should help to reduce the enormous disease burden from infections caused by multi-resistant E. coli, mainly ST131-H30.

Public Health Relevance

Infections caused by Escherichia coli ? such as urinary tract infections ? are extremely common among veterans and are increasingly antibiotic-resistant, making them harder to treat and resulting in worse clinical outcomes. Our proposed investigation of the source for these infections, the gut reservoir, and of the basis for the prolonged gut persistence of the most common antibiotic-resistant E. coli strain, ST131-H30 (including human behaviors, immune factors, bacterial genetic factors, and the gut microbiome), should help us to develop interventions against gut colonization with these troublesome strains. Such interventions can be expected to reduce the enormous number of ST131-H30 infections among veterans, with their huge disease burden and associated costs.

National Institute of Health (NIH)
Veterans Affairs (VA)
Non-HHS Research Projects (I01)
Project #
Application #
Study Section
Infectious Diseases B (INFB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Minneapolis VA Medical Center
United States
Zip Code
Mendis, Shehara M; Vasoo, Shawn; Johnston, Brian D et al. (2018) Clinical and Molecular Correlates of Escherichia coli Bloodstream Infection from Two Geographically Diverse Centers in Rochester, Minnesota, and Singapore. Antimicrob Agents Chemother 62:
Kanamori, Hajime; Parobek, Christian M; Juliano, Jonathan J et al. (2017) Genomic Analysis of Multidrug-Resistant Escherichia coli from North Carolina Community Hospitals: Ongoing Circulation of CTX-M-Producing ST131-H30Rx and ST131-H30R1 Strains. Antimicrob Agents Chemother 61:
Kisiela, Dagmara I; Radey, Matthew; Paul, Sandip et al. (2017) Inactivation of Transcriptional Regulators during Within-Household Evolution of Escherichia coli. J Bacteriol 199:
Johnson, James R (2017) Definition of Complicated Urinary Tract Infection. Clin Infect Dis 64:529
Johnson, James R; Drekonja, Dimitri M (2017) Bacteriuria/Pyuria of Clinically Undetermined Significance (BPCUS): Common, but Currently Nameless. Am J Med 130:e201-e204
Johnson, James R (2017) Definitions of Complicated Urinary Tract Infection and Pyelonephritis. Clin Infect Dis 64:390
Manges, Amee R; Mende, Katrin; Murray, Clinton K et al. (2017) Clonal distribution and associated characteristics of Escherichia coli clinical and surveillance isolates from a military medical center. Diagn Microbiol Infect Dis 87:382-385
Merino, Irene; Porter, Stephen B; Johnston, Brian D et al. (2017) Virulence genes and subclone status as markers of experimental virulence in a murine sepsis model among Escherichia coli sequence type 131 clinical isolates from Spain. PLoS One 12:e0188838
Johnson, James R (2017) Treatment of ED patients with bacteriuria/pyuria of clinically undetermined significance. Am J Emerg Med 35:1561
Johnson, James R; Porter, Stephen; Thuras, Paul et al. (2017) Epidemic Emergence in the United States of Escherichia coli Sequence Type 131-H30 (ST131-H30), 2000 to 2009. Antimicrob Agents Chemother 61:

Showing the most recent 10 out of 53 publications