Longitudinal Surveys Show that Urethral Catheters Harbor Recurrent Polymicrobial Biofilms with Cooperative and Competitive Behaviors Among Cohabitating Pathogens

Abstract

The analysis of catheter biofilms (CBs) from patients with neurogenic bladder disorders revealed persistent colonization by polymicrobial communities. The recurrence of bacterial species in the CBs of sequentially replaced catheters suggests urothelial reservoirs responsible for recolonization of the catheter surface. Proteomic data for CB samples were indicative of chronic inflammation in the patients urinary tracts via neutrophil and eosinophil infiltration and epithelial cell exfoliation. These host defense pathways, effective in killing pathogens during uncomplicated urinary tract infection, failed to eliminate CBs. Intermittent antibiotic drug treatment had different outcomes: either replacement of drug-susceptible by drug-tolerant bacteria or transient microbial biomass reduction followed by resurgence of the previously colonizing bacteria. Proteins that sequester iron and zinc such as lactotransferrin, lipocalin-2 and calprotectin were abundant in the patients CBs and urine sediments. Indicative of a host-pathogen battle for bivalent metal ions, acquisition and transport systems for such ions were highly expressed by many organisms residing in CBs. Species part of the Enterococcaceae and Aerococcaceae families, generally not well-characterized in their ability to synthesize siderophores, frequently cohabitated biofilms dominated by siderophore-producing Enterobacteriaceae. In support of metal acquisition cooperativity, we noticed positive abundance correlations for a Proteus mirabilis yersiniabactin-type siderophore system and two Enterococcus faecalis ABC transporters. Distinct bacterial strains highly expressed known or putative cytotoxins that appeared to compromise the survival of co-resident bacteria, e.g. a P. mirabilis hemolysin and Pseudomonas aeruginosa type 6 secretion and pyoverdin biosynthesis systems. In conclusion, there is support for cooperative and competitive behaviors among bacteria cohabitating CBs.