Klebsiella pneumoniae type 3 pili facilitate adherence and biofilm formation on abiotic surfaces

The aim of this study was to determine the diversity of Klebsiella pneumoniae capsular serotypes in an Australian setting. Consecutive (n ‫؍‬ 293) nonrepetitive isolates of K. pneumoniae from a large teaching hospital laboratory were analyzed. The majority of isolates were from urinary specimens (60.8%); the next most common source was sputum (14.3%), followed by blood (14%). Serotyping revealed a wide range of capsule types. K54 (17.1%), K28 (4.1%), and K17 (3.1%) were the most common, and K54 isolates displayed a high degree of clonality, suggesting a common, nosocomial source. In vitro, one K54 isolate was more adherent to urinary catheters and HEp-2 cells than four other tested isolates; it was slightly more resistant to chlorhexidine but was more susceptible to drying than heavily encapsulated strains. This is the first seroprevalence survey of K. pneumoniae to be performed on Australian isolates, and the high level of diversity of serotypes suggests that capsule-based immunoprophylaxis might not be useful for Australia. In addition there are significant differences in the predominance of specific serotypes compared to the results of surveys performed overseas, which has important implications for capsule-based immunoprophylaxis aimed at a global market.

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“…polymers (11,17,28). There are several reports linking adhesive phenotypes of K. pneumoniae to nosocomial infection (10,12,20).…”

Section: Discussionmentioning

confidence: 99%

Seroepidemiology ofKlebsiella pneumoniaein an Australian Tertiary Hospital and Its Implications for Vaccine Development

et al. 2006

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“…Biofilms develop in natural aquatic systems, water pipes, on the teeth, on medical devices [15]. The signals that promote biofilm rapid formation are: (i) presence of a suitable surface; (ii) increase of extracellular iron; (iii) presence of indole, polyamines, calcium and bile salts [75][76][77]. In the initial phase of biofilm formation, bacterial attacks proliferate, forming microcolonies and attracting surrounding cells.…”

Section: Agnps Antibiofilm Activitymentioning

confidence: 99%

Silver Nanoparticles as Potential Antibacterial Agents

et al. 2015

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Multi-drug resistance is a growing problem in the treatment of infectious diseases and the widespread use of broad-spectrum antibiotics has produced antibiotic resistance for many human bacterial pathogens. Advances in nanotechnology have opened new horizons in nanomedicine, allowing the synthesis of nanoparticles that can be assembled into complex architectures. Novel studies and technologies are devoted to understanding the mechanisms of disease for the design of new drugs, but unfortunately infectious diseases continue to be a major health burden worldwide. Since ancient times, silver was known for its anti-bacterial effects and for centuries it has been used for prevention and control of disparate infections. Currently nanotechnology and nanomaterials are fully integrated in common applications and objects that we use every day. In addition, the silver nanoparticles are attracting much interest because of their potent antibacterial activity. Many studies have also shown an important activity of silver nanoparticles against bacterial biofilms. This review aims to OPEN ACCESSMolecules 2015, 20 8857 summarize the emerging efforts to address current challenges and solutions in the treatment of infectious diseases, particularly the use of nanosilver antimicrobials.

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“…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).…”

mentioning

confidence: 99%

“…The MrkA protein is the pilin fibrial subunit, MrkB and MrkC function as the periplasmic chaperone and usher translocase for MrkA, and MrkD forms the tip adhesion subunit (10)(11)(12)(13). Studies showed that type 3 fimbriae can adhere to a number of inert surfaces that are present on biomedical devices such as polystyrene, polypropylene, glass, and stainless steel (6)(7)(8)(9)(10)(11)(12)(13)(14). The expression of type 3 fimbriae components was recently shown to be activated by increasing intracellular concentrations of the second messenger, 3′,5′-cyclic diguanylic acid (c-di-GMP) (7).…”

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confidence: 99%

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

Schumacher

Zhang

2016

Proc. Natl. Acad. Sci. U.S.A.

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The pathogenesis of Klebsiella pneumonia is linked to the bacteria’s ability to form biofilms. Mannose-resistant Klebsiella-like (Mrk) hemagglutinins are critical for K. pneumonia biofilm development, and the expression of the genes encoding these proteins is activated by a 3′,5′-cyclic diguanylic acid (c-di-GMP)–regulated transcription factor, MrkH. To gain insight into MrkH function, we performed structural and biochemical analyses. Data revealed MrkH to be a monomer with a two-domain architecture consisting of a PilZ C-domain connected to an N domain that unexpectedly also harbors a PilZ-like fold. Comparison of apo- and c-di-GMP–bound MrkH structures reveals a large 138° interdomain rotation that is induced by binding an intercalated c-di-GMP dimer. c-di-GMP interacts with PilZ C-domain motifs 1 and 2 (RxxxR and D/NxSxxG) and a newly described c-di-GMP–binding motif in the MrkH N domain. Strikingly, these c-di-GMP–binding motifs also stabilize an open state conformation in apo MrkH via contacts from the PilZ motif 1 to residues in the C-domain motif 2 and the c-di-GMP–binding N-domain motif. Use of the same regions in apo structure stabilization and c-di-GMP interaction allows distinction between the states. Indeed, domain reorientation by c-di-GMP complexation with MrkH, which leads to a highly compacted structure, suggests a mechanism by which the protein is activated to bind DNA. To our knowledge, MrkH represents the first instance of specific DNA binding mediated by PilZ domains. The MrkH structures also pave the way for the rational design of inhibitors that target K. pneumonia biofilm formation.

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Klebsiella pneumoniae type 3 pili facilitate adherence and biofilm formation on abiotic surfaces

Cited by 157 publications

References 55 publications

Seroepidemiology ofKlebsiella pneumoniaein an Australian Tertiary Hospital and Its Implications for Vaccine Development

Seroepidemiology ofKlebsiella pneumoniaein an Australian Tertiary Hospital and Its Implications for Vaccine Development

Silver Nanoparticles as Potential Antibacterial Agents

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

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