Cooccurrence of Antibiotic Resistance and Hypervirulence in High-Risk Carbapenem-Resistant K14.K64 and Wzi209 Klebsiella pneumoniae Strains Driven by Plasmids and Their Derivatives

Abstract

Currently, an increasing number of hv-CRKP strains have been reported and pose a substantial threat to public health worldwide, because these strains are considered to be simultaneously hypervirulent, carbapenem resistant, and transmissible. In this study, we provided a complete transition process of CRKP and hv-CRKP from their early emergence to outbreak in 10 years. Emerging hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) is a severe public health problem worldwide. To assess the cooccurrence of CRKP and hv-CRKP, a total of 1,181 CRKP isolates were collected from 2009 to 2018, covering their initial occurrence to outbreaks. Overall, two major capsular serotypes, namely, wzi209-CRKP and K14.K64-CRKP, were identified as being prevalent in pediatric and adult patients, respectively. Most isolates carried bla KPC , and the bla KPC -carrying hybrid plasmid IncFII-IncR, which was stable and transferable, was identified. The conjugation region ( traN / traC ) of IncFII-IncR was found to be variable, and the genes were used as markers to identify the transmission of strains among patient groups in this study. Notably, hv-CRKP was characterized by screening for four virulence genes ( rmpA , iroN , terW , and rmpA2 ) in all 977 bla KPC -carrying K14.K64-CRKP and wzi209-CRKP strains. Two virulence types, namely, rmpA / iroN / terW / rmpA2 positive and terW / rmpA2 positive, were found. The corresponding virulence plasmids Vir1, i.e., nonconjugative IncFIB(k)-IncHI1B, and Vir2, i.e., conjugative antibiotic-resistant IncFIB-IncHI1B, were further characterized. Both Vir1 and Vir2 were stable, and the transferability of Vir2 was significantly higher than that of IncFII-IncR. However, none of the Vir1- or Vir2-carrying strains exhibited the hypervirulent phenotype. Meanwhile, hv-CRKP ( terW / rmpA2 positive) was found in late 2018 among wzi209-CRKP strains. The corresponding Vir2-related fragment was characterized as chromosomally integrated, which dramatically enhanced the virulence of wzi209-CRKP. Transmission of hv-CRKP among patient groups was also confirmed according to virulence elements. Taken together, CRKP and hv-CRKP occurred on a large scale. Plasmids and their derivatives played an important role on this process. Surveillance and intervention of hv-CRKP are urgently needed. IMPORTANCE Currently, an increasing number of hv-CRKP strains have been reported and pose a substantial threat to public health worldwide, because these strains are considered to be simultaneously hypervirulent, carbapenem resistant, and transmissible. In this study, we provided a complete transition process of CRKP and hv-CRKP from their early emergence to outbreak in 10 years. We identified two epidemic groups, K14.K64 (wzi64)-CRKP and wzi209-CRKP, in adult and pediatric patients, respectively. K14.K64 (wzi64)-CRKP was widely present, while wzi209-CRKP was rarely reported as an epidemic type. We discovered a large scale of hv-CRKP transmission from CRKP and determined the importance of antibiotic resistance and virulence plasmids and their derivatives for the transition of CRKP and hv-CRKP. Two virulence plasmids coexist in out hospital, but neither of them enhanced virulence. Notably, we found a newly emerged type of CRKP, hypervirulent wzi209-CRKP, which had dramatically enhanced virulence, making it a great threat to human health.