Inhibiting Host Protein Deposition on Urinary Catheters Reduces Urinary Tract Infections
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Enterococcus Faecalis (ncbitaxon:1351) Mus Musculus (ncbitaxon:10090)
SUBMITTER: 
Ana Lidia Flores-Mireles Marissa Jeme Andersen Matthew Champion
PROVIDER: MSV000088527 | MassIVE | Mon Dec 06 12:41:00 GMT 2021
REPOSITORIES: MassIVE
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Project description:Chronic bacterial infections on medical devices, including catheter-associated urinary tract infections (CAUTI), are associated with bacterial biofilm communities that are refractory to antibiotic therapy and resistant to host immunity. Previously, we have shown that Pseudomonas aeruginosa can cause CAUTI by forming a device-associated biofilm that is independent of known biofilm exopolysaccharides. Here, we show by RNA-seq that host urine alters the transcriptome of P. aeruginosa by suppressing quorum sensing regulated genes. P. aeruginosa produces acyl homoserine lactones (AHLs) in the presence of urea, but cannot perceive AHLs. Repression of quorum sensing by urine implies that quorum sensing should be dispensable during infection of the urinary tract. Indeed, mutants defective in quorum sensing are able to colonize similarly to wild-type in a murine model of CAUTI. Quorum sensing-regulated processes in clinical isolates are also inhibited by urea. These data show that urea in urine is a natural anti-quorum sensing mechanism in mammals.
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Project description:Urinary tract infections (UTIs) are common, recurrent infections that can be mild to life-threatening. The continued emergence of antibiotic resistance, together with our increasing understanding of the detrimental effects conferred by broad-spectrum antibiotic use on the health of the beneficial microbiota of the host, has underscored the weaknesses in our current treatment paradigm for UTIs. In this Review, we discuss how recent microbiological, structural, genetic and immunological studies have expanded our understanding of host-pathogen interactions during UTI pathogenesis. These basic scientific findings have the potential to shift the strategy for UTI treatment away from broad-spectrum antibiotics targeting conserved aspects of bacterial replication towards pathogen-specific antibiotic-sparing therapeutics that target core determinants of bacterial virulence at the host-pathogen interface.
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Project description:The urinary tract is constantly exposed to different microorganisms that colonize the gastrointestinal tract and the urinary tract is normally well prepared to resist infections by these microorganisms. This resistance to infection is mainly accomplished by the versatility of the immune system in the urinary tract, with both innate and adaptive immune responses. With the increasing knowledge of how the immune system works in the urinary tract and also the recognition of the virulence attributes of uropathogens, several potentially effective and tailored strategies to contain or prevent urinary tract infections have emerged.
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Project description:A urinary tract infection (UTI) is a collective term for infections that involve any part of the urinary tract. It is one of the most common infections in local primary care. The incidence of UTIs in adult males aged under 50 years is low, with adult women being 30 times more likely than men to develop a UTI. Appropriate classification of UTI into simple or complicated forms guides its management and the ORENUC classification can be used. Diagnosis of a UTI is based on a focused history, with appropriate investigations depending on individual risk factors. Simple uncomplicated cystitis responds very well to oral antibiotics, but complicated UTIs may require early imaging, and referral to the emergency department or hospitalisation to prevent urosepsis may be warranted. Escherichia coli remains the predominant uropathogen in acute community-acquired uncomplicated UTIs and amoxicillin-clavulanate is useful as a first-line antibiotic. Family physicians are capable of managing most UTIs if guided by appropriate history, investigations and appropriate antibiotics to achieve good outcomes and minimise antibiotic resistance.
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Project description:Proteus mirabilis is a Gram-negative bacterium and is well known for its ability to robustly swarm across surfaces in a striking bulls'-eye pattern. Clinically, this organism is most frequently a pathogen of the urinary tract, particularly in patients undergoing long-term catheterization. This review covers P. mirabilis with a focus on urinary tract infections (UTI), including disease models, vaccine development efforts, and clinical perspectives. Flagella-mediated motility, both swimming and swarming, is a central facet of this organism. The regulation of this complex process and its contribution to virulence is discussed, along with the type VI-secretion system-dependent intra-strain competition, which occurs during swarming. P. mirabilis uses a diverse set of virulence factors to access and colonize the host urinary tract, including urease and stone formation, fimbriae and other adhesins, iron and zinc acquisition, proteases and toxins, biofilm formation, and regulation of pathogenesis. While significant advances in this field have been made, challenges remain to combatting complicated UTI and deciphering P. mirabilis pathogenesis.
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Project description:Urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC) strains. In contrast to many enteric E. coli pathogroups, no genetic signature has been identified for UPEC strains. We conducted a high-resolution comparative genomic study using E. coli isolates collected from the urine of women suffering from frequent recurrent UTIs. These isolates were genetically diverse and varied in their urovirulence, that is, their ability to infect the bladder in a mouse model of cystitis. We found no set of genes, including previously defined putative urovirulence factors (PUFs), that were predictive of urovirulence. In addition, in some patients, the E. coli strain causing a recurrent UTI had fewer PUFs than the supplanted strain. In competitive experimental infections in mice, the supplanting strain was more efficient at colonizing the mouse bladder than the supplanted strain. Despite the lack of a clear genomic signature for urovirulence, comparative transcriptomic and phenotypic analyses revealed that the expression of key conserved functions during culture, such as motility and metabolism, could be used to predict subsequent colonization of the mouse bladder. Together, our findings suggest that UTI risk and outcome may be determined by complex interactions between host susceptibility and the urovirulence potential of diverse bacterial strains.
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