Abstract
Increasing numbers of pyelonephritis-associated uropathogenic Escherichia coli (UPEC) are exhibiting high resistance to antibiotic therapy. They include a particular clonal group, the CTX-M-15-producing O25b:H4-ST131 clone, which has been shown to have a high dissemination potential. Here we show that a representative isolate of this E. coli clone, referred to as TN03, has enhanced metabolic capacities, acts as a potent intestine- colonizing strain, and displays the typical features of UPEC strains. In a modified streptomycin-treated mouse model of intestinal colonization where streptomycin was stopped 5 days before inoculation, we show that TN03 outcompetes the commensal E. coli strains K-12 MG1655, IAI1, and ED1a at days 1 and 7. Using an experimental model of ascending UTI in C3H/HeN mice, we then show that TN03 colonized the urinary tract. One week after the transurethral inoculation of the TN03 isolates, the bacterial loads in the bladder and kidneys were significantly greater than those of two other UPEC strains (CFT073 and HT7) belonging to the same B2 phylogenetic group. The differences in bacterial loads did not seem to be directly linked to differences in the inflammatory response, since the intrarenal expression of chemokines and cytokines and the number of polymorphonuclear neutrophils attracted to the site of inflammation was the same in kidneys colonized by TN03, CFT073, or HT7. Lastly, we show that in vitro TN03 has a high maximum growth rate in both complex (Luria-Bertani and human urine) and minimum media. In conclusion, our findings indicate that TN03 is a potent UPEC strain that colonizes the intestinal tract and may persist in the kidneys of infected hosts.
Highlights
Urinary tract infections (UTIs) are one of the bacterial infections that most often affect children, young adults, and renal transplanted patients
The TN03 strain is a potent colonizer of the intestine Infection of the urinary tract presumably begins with the colonization of the bowel by a uropathogenic strain [15], as suggested by the fact that the uropathogenic Escherichia coli (UPEC) isolates present in infected urine are almost always detectable in the host’s fecal flora at the time of presentation [16]
The bacteria were mixed in a 1:1 ratio of TN03 with commensal E. coli K-12 MG1655, IAI1, or ED1a bacteria. 106 of this bacterial mix was administered per os to the mice as described above, The sizes of the bacterial populations in the intestine were evaluated at days 1, 2, 4 and 7 following inoculation
Summary
Urinary tract infections (UTIs) are one of the bacterial infections that most often affect children, young adults, and renal transplanted patients. In 2008, two research groups, analyzing the population of E. coli ESBL-producing strains, described a particular CTX-M-15-producing clonal group This clone occurred in both in-patients and out-patients worldwide, strongly suggesting that it is widely disseminated [6,7], which constitutes a major health problem [8,9]. Such bacterial resistance frequently delays the establishment of appropriate therapy [10], leading to higher costs and increased use of the ‘‘last resort’’ antimicrobials (i.e. carbapenems) [5]. This ST131 sequence type has been detected in companion animals, non-companion animals, and food [12]
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