Kpi, a Chaperone-Usher Pili System Associated with the Worldwide-Disseminated High-Risk Clone Klebsiella Pneumoniae ST-15

Control of infections caused by carbapenem-resistant Klebsiella pneumoniae continues to be challenging. The success of this pathogen is favored by its ability to acquire antimicrobial resistance and to spread and persist in both the environment and in humans.The emergence of clinically important clones, such as sequence types 11, 15, 101, and 258, has been reported worldwide. However,the mechanisms promoting the dissemination of such highrisk clones are unknown. Unraveling the factors that play a role in the pathobiology and epidemicity of K. pneumoniae is therefore important for managing infections. To address this issue, we studied a carbapenem-resistant ST-15 K. pneumoniae isolate (Kp3380) that displayed a remarkable adherent phenotype with abundant pilus-like structures. Genome sequencing enabled us to identify a chaperone-usher pili system (Kpi) in Kp3380. Analysis of a large K. pneumoniae population from 32 European countries showed that the Kpi system is associated with the ST-15 clone. Phylogenetic analysis of the operon revealed that Kpi belongs to the littlecharacterized γ2-fimbrial clade. We demonstrate that Kpi contributes positively to the ability of K.pneumoniae to form biofilms and adhere to different host tissues. Moreover, the in vivo intestinal colonizing capacity of the Kpi-defective mutant was significantly reduced, as was its ability to infect Galleria mellonella. The findings provide information about the pathobiology and epidemicity of Kpi+ K. pneumoniae and indicate that the presence of Kpi may explain the success of the ST-15 clone. Disrupting bacterial adherence to the intestinal surface could potentially target gastrointestinal colonization.
This research was supported by Projects p-01216A and IJCI-2016-29524 (to A.P.), funded by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Minestry of Economy and Competetiveness(MINECO), respectively. It was also supported by Projects PI11/01034 (to M.P.), PI14/00059 and PI17/1482 (to M.P. and A.B.), and PI18/00501 (to G.B.),included in the National Plan for Scientific Research, Development and Technological Innovation 2013-2016 and funded by the Instituto de Salud Carlos III (ISCIII) and Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/006) cofinanced by European Development Regional Fund “A way to achieve Europe” and operative program Intelligent Growth 2014-2020. Grant BFU2016-77835-R of the MINECO (to A.R.) also supported this research. E.G. was financially supported by the SEIMC project. J.C.V.-U. was financially supported by the PFIS (Contratos Predoctorales de Formación en Investigación en Salud) program (F18/00315);J.A.V. was financially supported by IN607A 2016/22; M.M.-G. was financially supported by a Clara Roy grant (SEIMC); A.B. was financially supported by the Miguel Servet program (ISCIII, Spain); B.K.R.-J. was financially supported by Marie S. Curie Action SaPhaDe project (MSCA-IF-GF-836754); and A.P. was financially supported by the Juan de la Cierva program (MINECO, IJCI-2016-29524).