An in vitro dynamic model of catheter-associated urinary tract infections to investigate the role of uncommon bacteria on the Escherichia coli microbial consortium

Abstract

About 9% of nosocomial infections are attributed to catheter-associated urinary tract infections (CAUTIs). Uncommon bacteria (Delftia tusurhatensis) have been isolated in CAUTIs in combination with wellestablished pathogenic bacteria such as E. coli. Nonetheless, the reason why E. coli coexists with other bacteria instead of outcompeting and completely eliminating them are unknown. As such, a flow cell reactor simulating the hydrodynamic conditions found in CAUTIs (shear rate of 15 s-1) was used to characterize the microbial physiology of E. coli and D. tsuruhatensis individually and in consortium, in terms of growth kinetics and substrate uptake. Single-species biofilms showed that up to 48 h the CFU counts significantly increased for both species (p<0.05). After 48 h, both species stabilized with similar CFU values reaching log 6.24 CFU.cm2 for E. coli and log 6.31 CFU.cm2 for D. tsuruhatensis (p>0.05). The assessment of spatial distribution of dual-species biofilms by LNA/2´OMe-FISH revealed that E. coli and D. tsuruhatensis coexist and tend to co-aggregate over time, which implies that bacteria are able to cooperate synergistically. Substrate uptake measurements revealed that in artificial urine medium the bacteria metabolized lactic acid, uric acid (E. coli and D. tsuruhatensis) and citric acid (D. tsuruhatensis). In the consortium, D. tsuruhatensis consumed citric acid more rapidly, presumably leaving more uric acid available in the medium to be used by E. coli. In conclusion, metabolic cooperation between E. coli and uncommon species seems to occur when these species share the same environment, leading to the formation of a stable microbial community.