A specific group of Escherichia coli, sequence type ST131 is a newly recognized, widely disseminated cause of multi-drug-resistant (MDR extraintestinal infections that appears to represent an important emerging health threat in urgent need of study. Therefore, we propose to test the following Hypotheses by accomplishing the following Specific Aims: 1. ST131 has emerged in the past ten years as the predominant FQ-R E. coli clonal group in the US, including among veterans.
Aim 1. Assess the annual prevalence of ST131 in the US among FQ-R and FQ-S E. coli in the SENTRY and TRUST collections (1999-2009) and from VA medical centers nationwide (2009). 2. ST131 is more fit than other E. coli in the pathogenic and commensal niches, and is present in foods. 2.a. In humans, ST131 causes more severe infections, in less compromised hosts, than other E. coli.
Aim 2. a. Compare clinical presentation (syndrome and severity), illness outcome, and host compromise status among veterans with ST131 vs. non-ST131 E. coli clinical isolates. 2.b. In mice, ST131 is more virulent (UTI, sepsis) than other E. coli, including classic ExPEC strains.
Aim 2. b. Compare the virulence of ST131 isolates, non-ST131 clinical isolates, and classic ExPEC strains. 2.c. ST131 exhibits enhanced intestinal colonization and host-to-host transmission, vs. other E.
coli Aim 2. c.1. In humans, assess the prevalence of intestinal co-colonization among household members of index patients with ST131 vs. non-ST131 FQ-R E. coli clinical isolates.
Aim 2. c.2. In mice, compare ST131 with non-ST131 E. coli for establishment of intestinal colonization after direct challenge or indirect exposure. 2.d. ST131 is present in retail foods, consistent with foodborne transmission.
Aim 2. d.1. Determine the prevalence of ST131 in diverse retail foods.
Aim 2. d.2. Assess the similarity of food-source versus human-source ST131 isolates according to genomic background, virulence genotype, and resistance profile. 3. Specific host characteristics predict ST131 infection.
Aim 3. Compare demographics and exposures among veterans with ST131 infection versus concurrent controls with non-ST131 E. coli infection. 4. ST131 is more receptive to CTX-M-15-encoding genetic elements than are other E. coli.
Aim 4. Compare transfer frequencies for CTX-M-15 (vs. other ESBL)-encoding elements from ST131 (vs. non-ST131) donors to ST131 (vs. non-ST131) recipients.

Public Health Relevance

Relevance to Veterans Health. Veterans commonly suffer from UTI and diverse other E. coli infections (e.g. of lung, abdomen, and wounds) [16]. Emerging antimicrobial resistance in E. coli increases the risk that veterans will receive inappropriate initial antimicrobial therapy, and makes appropriate therapy more expensive, potentially toxic, and difficult to administer.

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
Liu, Cindy M; Stegger, Marc; Aziz, Maliha et al. (2018) Escherichia coli ST131-H22 as a Foodborne Uropathogen. MBio 9:
Johnson, James R; Johnston, Brian D; Delavari, Parissa et al. (2017) Phylogenetic Backgrounds and Virulence-Associated Traits of Escherichia coli Isolates from Surface Waters and Diverse Animals in Minnesota and Wisconsin. Appl Environ Microbiol 83:
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:
Han, Jennifer H; Garrigan, Charles; Johnston, Brian et al. (2017) Epidemiology and characteristics of Escherichia coli sequence type 131 (ST131) from long-term care facility residents colonized intestinally with fluoroquinolone-resistant Escherichia coli. Diagn Microbiol Infect Dis 87:275-280
Johnson, James R; Porter, Stephen; Thuras, Paul et al. (2017) The Pandemic H30 Subclone of Sequence Type 131 (ST131) as the Leading Cause of Multidrug-Resistant Escherichia coli Infections in the United States (2011-2012). Open Forum Infect Dis 4:ofx089
Johnson, James R; Thuras, Paul; Johnston, Brian D et al. (2016) The Pandemic H30 Subclone of Escherichia coli Sequence Type 131 Is Associated With Persistent Infections and Adverse Outcomes Independent From Its Multidrug Resistance and Associations With Compromised Hosts. Clin Infect Dis 62:1529-1536
Johnson, Timothy J; Danzeisen, Jessica L; Youmans, Bonnie et al. (2016) Separate F-Type Plasmids Have Shaped the Evolution of the H30 Subclone of Escherichia coli Sequence Type 131. mSphere 1:
Drekonja, Dimitri M; Kuskowski, Michael A; Anway, Ruth et al. (2016) The Niche for Escherichia coli Sequence Type 131 Among Veterans: Urinary Tract Abnormalities and Long-Term Care Facilities. Open Forum Infect Dis 3:ofw138
Stoesser, Nicole; Sheppard, Anna E; Pankhurst, Louise et al. (2016) Evolutionary History of the Global Emergence of the Escherichia coli Epidemic Clone ST131. MBio 7:e02162
Mohamed, Muhanad; Clabots, Connie; Porter, Stephen B et al. (2016) Isolation and Characterization of Escherichia coli Sequence Type 131 and Other Antimicrobial-Resistant Gram-Negative Bacilli from Clinical Stool Samples from Veterans. Antimicrob Agents Chemother 60:4638-45

Showing the most recent 10 out of 60 publications