Widespread Detection of Yersiniabactin Gene Cluster and Its Encoding Integrative Conjugative Elements (ICE Kp ) among Nonoutbreak OXA-48-Producing Klebsiella pneumoniae Clinical Isolates from Spain and the Netherlands.

In this study, we determined the presence of virulence factors in nonoutbreak, high-risk clones and other isolates belonging to less common sequence types associated with the spread of OXA-48-producing Klebsiella pneumoniae clinical isolates from The Netherlands ( n  = 61) and Spain ( n  = 53). Most isolates shared a chromosomally encoded core of virulence factors, including the enterobactin gene cluster, fimbrial fim and mrk gene clusters, and urea metabolism genes ( ureAD ). We observed a high diversity of K-Locus and K/O loci combinations, KL17 and KL24 (both 16%), and the O1/O2v1 locus (51%) being the most prevalent in our study. The most prevalent accessory virulence factor was the yersiniabactin gene cluster (66.7%). We found seven yersiniabactin lineages- ybt  9, ybt  10, ybt  13, ybt  14, ybt  16, ybt  17, and ybt  27-which were chromosomally embedded in seven integrative conjugative elements (ICE Kp ): ICE Kp3 , ICE Kp4 , ICE Kp2 , ICE Kp5 , ICE Kp12 , ICE Kp10 , and ICE Kp22 , respectively. Multidrug-resistant lineages-ST11, ST101, and ST405-were associated with ybt  10/ICE Kp4 , ybt  9/ICE Kp3 , and ybt  27/ICE Kp22 , respectively. The fimbrial adhesin kpi operon ( kpiABCDEFG ) was predominant among ST14, ST15, and ST405 isolates, as well as the ferric uptake system kfuABC , which was also predominant among ST101 isolates. No convergence of hypervirulence and resistance was observed in this collection of OXA-48-producing K. pneumoniae clinical isolates. Nevertheless, two isolates, ST133 and ST792, were positive for the genotoxin colibactin gene cluster (ICE Kp10 ). In this study, the integrative conjugative element, ICE Kp , was the major vehicle for yersiniabactin and colibactin gene clusters spreading. IMPORTANCE Convergence of multidrug resistance and hypervirulence in Klebsiella pneumoniae isolates has been reported mostly related to sporadic cases or small outbreaks. Nevertheless, little is known about the real prevalence of carbapenem-resistant hypervirulent K. pneumoniae since these two phenomena are often separately studied. In this study, we gathered information on the virulent content of nonoutbreak, high-risk clones (i.e., ST11, ST15, and ST405) and other less common STs associated with the spread of OXA-48-producing K. pneumoniae clinical isolates. The study of virulence content in nonoutbreak isolates can help us to expand information on the genomic landscape of virulence factors in K. pneumoniae population by identifying virulence markers and their mechanisms of spread. Surveillance should focus not only on antimicrobial resistance but also on virulence characteristics to avoid the spread of multidrug and (hyper)virulent K. pneumoniae that may cause untreatable and more severe infections.
Competing Interests: The authors declare a conflict of interest. J.W.A.R. was employed by IDbyDNA and is currently consulting for ARES-genetics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.