Role of Klebsiella pneumoniae Type 1 and Type 3 Fimbriae in Colonizing Silicone Tubes Implanted into the Bladders of Mice as a Model of Catheter-Associated Urinary Tract Infections

Abstract

bCatheter-associated urinary tract infections are biofilm-mediated infections that cause a significant economic and health burden in nosocomial environments. Using a newly developed murine model of this type of infection, we investigated the role of fimbriae in implant-associated urinary tract infections by the Gram-negative bacterium Klebsiella pneumoniae, which is a proficient biofilm former and a commonly isolated nosocomial pathogen. Studies have shown that type 1 and type 3 fimbriae are involved in attachment and biofilm formation in vitro, and these fimbrial types are suspected to be important virulence factors during infection. To test this hypothesis, the virulence of fimbrial mutants was assessed in independent challenges in which mouse bladders were inoculated with the wild type or a fimbrial mutant and in coinfection studies in which the wild type and fimbrial mutants were inoculated together to assess the results of a direct competition in the urinary tract. Using these experiments, we were able to show that both fimbrial types serve to enhance colonization and persistence. Additionally, a double mutant had an additive colonization defect under some conditions, indicating that both fimbrial types have unique roles in the attachment and persistence in the bladder and on the implant itself. All of these mutants were outcompeted by the wild type in coinfection experiments. Using these methods, we are able to show that type 1 and type 3 fimbriae are important colonization factors in the murine urinary tract when an implanted silicone tube is present.

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

“…This idea is supported by work done with a mouse model of catheter-associated UTI, where the presence of a catheter allowed the persistence of K. pneumoniae in the bladder for at least 48 h postinfection (hpi). In contrast, clearance of K. pneumoniae was observed in the absence of a catheter (302). In this model, colonization and persistence in the bladder and on the catheter were facilitated by type 1 and 3 fimbriae.…”

Positive Autoregulation ofmrkHIby the Cyclic Di-GMP-Dependent MrkH Protein in the Biofilm Regulatory Circuit of Klebsiella pneumoniae

“…K. pneumoniae isolates express two different, well-characterized fimbrial structures that are involved in surface attachment-the type 1 and type 3 fimbriae (4,5,(11)(12)(13)(14)(15)(16). FimK regulates type 1 fimbriation through a phase- …”

“…K. pneumoniae isolates express two different, well-characterized fimbrial structures that are involved in surface attachment-the type 1 and type 3 fimbriae (4,5,(11)(12)(13)(14)(15)(16). FimK regulates type 1 fimbriation through a phase-variation process (17), while type 3 fimbrial production is controlled by MrkH, a novel c-di-GMP-dependent transcriptional activator (7,8,10,18) that binds to a nucleotide sequence known as the "MrkH box" that is located upstream of the type 3 fimbrial operon, mrkABCDF (9).…”

“…Klebsiella pneumoniae is a Gram-negative, opportunistic pathogen that is frequently associated with nosocomial infections such as pneumonia, urinary tract infections, and septicemia (1). An important clinical pathogenic mechanism of K. pneumoniae is its ability to form biofilms on inert surfaces such as medical devices, which can lead to rapid microbial colonization on host tissues (2)(3)(4)(5)(6).…”

Structures of the activator of K. pneumonia biofilm formation, MrkH, indicates PilZ domains involved in c-di-GMP and DNA binding

“…The pathogenicity of K. pneumonia is associated with its ability to form biofilms, which are largely recalcitrant to treatment (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Key to K. pneumonia biofilm development are mannose-resistant Klebsiella-like (Mrk) hemagglutinins or Mrk proteins, which are encoded by the mrkABCDF operon (7)(8)(9)(10)(11)(12)(13)(14).…”