RESUMEN
BACKGROUND: Urinary tract infection (UTI) is a common disease with a significant risk of relapse. Deliberate bladder colonization with asymptomatic Escherichia coli is being explored as a potential strategy to fend off invading uropathogens thereby mitigating the risk symptomatic UTI. Currently, one major obstacle is the low success rates for achieving persistent bladder colonization with asymptomatic bacteria and experimental challenge studies are lacking. Here, we assessed the influence of an indwelling bladder catheter on the ability of asymptomatic E. coli to colonize the bladder and to assess the protective efficacy of such colonization against experimental urinary tract infection with uropathogenic E. coli. METHODS: Pigs with or without indwelling bladder catheters were experimentally inoculated with the asymptomatic E. coli strain 83972 and subsequently challenged by inoculation with the uropathogenic E. coli isolate, UTI89. The animals were monitored with regular urine and blood samples and bladders and kidneys were harvested at termination. RESULTS: All pigs with indwelling catheters were colonized by 83972 in response to inoculation, compared to pigs without catheters in which only one of eight animals were colonized. When removing the catheter, 83972 were spontaneously cleared. Colonization with 83972 prevented experimental infection in 50% of animals compared to controls that all became infected. CONCLUSIONS: The presence of indwelling bladder catheters strongly facilitates the colonization of 83972, indicating that individuals using catheters may be particularly suited for receiving this treatment. The research supports prophylactic colonization with 83972 as a potential strategy to reduce the risk of urinary tract infections.
RESUMEN
Two-component systems are key signal-transduction systems that enable bacteria to respond to a wide variety of environmental stimuli. The human pathogen, Streptococcus pneumoniae (pneumococcus) encodes 13 two-component systems and a single orphan response regulator, most of which are significant for pneumococcal pathogenicity. Mapping the regulatory networks governed by these systems is key to understand pneumococcal host adaptation. Here we employ a novel bioinformatic approach to predict the regulons of each two-component system based on publicly available whole-genome sequencing data. By employing pangenome-wide association studies (panGWAS) to predict genotype-genotype associations for each two-component system, we predicted regulon genes of 11 of the pneumococcal two-component systems. Through validation via next-generation RNA-sequencing on response regulator overexpression mutants, several top candidate genes predicted by the panGWAS analysis were confirmed as regulon genes. The present study presents novel details on multiple pneumococcal two-component systems, including an expansion of regulons, identification of candidate response regulator binding motifs, and identification of candidate response regulator-regulated small non-coding RNAs. We also demonstrate a use for panGWAS as a complementary tool in target gene identification via identification of genotype-to-genotype links. Expanding our knowledge on two-component systems in pathogens is crucial to understanding how these bacteria sense and respond to their host environment, which could prove useful in future drug development.