Convergence of carbapenem resistance and hypervirulence in a highly-transmissible ST11 clone of K. pneumoniae: An epidemiological, genomic and functional study

Abstract

Co-occurrence of hypervirulence and KPC-2 carbapenem resistant phenotypes in a highly-transmissible ST11 clone of Klebsiella pneumoniae has elicited deep concerns from public health stand point. To address this puzzle, we conducted a large-scale epidemiological, clinical and genomic study of K. pneumonia ST11 clones with both hypervirulence and carbapenem resistance in two tertiary hospitals in Zhejiang province. Most of the patients (15/23) were diagnosed with exclusively carbapenem-resistant K . pneumoniae (CRKP) infections. Ten death cases were reported, some of which are due to the failure of antibiotic therapies. As a result, we identified one new rare sequence types (ST449) to KPC-2-producing CRKP, in addition to the dominant ST11. These clinical isolates of K. pneumoniae are multi-drug resistant and possess a number of virulence factors. Experimental infections of wax moth larvae revealed the presence of hypervirulence at varied level, suggesting the complexity in bacterial virulence factors. However, plasmid curing assays further suggested that the rmpA2 -virulence plasmid is associated with, but not sufficient for neither phenotypic hypermucoviscosity nor virulence of K . pneumoniae . Intriguingly, all the rmpA2 genes were found to be inactive due to genetic deletion. In total, we reported 21 complete plasmid sequences comprising 13 rmpA2 -positive virulence plasmids and 8 bla KPC-2 -harboring resistance plasmids. In addition to the prevalent pLVKP-like virulence plasmid variants (~178kb), we found an unexpected diversity among KPC-2-producing plasmids whose dominant form is IncFII-IncR type (~120kb), rather than the previously anticipated version of ~170kb. These findings provide an updated snapshot of convergence of hypervirulence and carbapenem resistance in ST11 K. pneumoniae.

Aerobactin Seems To Be a Promising Marker Compared With Unstable RmpA2 for the Identification of Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae: In Silico and In Vitro Evidence

“…Hypervirulent (Hv) Klebsiella pneumoniae (Kp) is a notorious pathogen causing a wide spectrum of infections in immunocompetent patients as well as immunosuppressed patients ( Shon et al, 2013 ). This pathotype is being increasingly reported in the last decade among community- and healthcare-associated infections and has acquired antimicrobial resistance, unlike its former counterpart ( Zhan et al, 2017 ; Hao et al, 2020 ; Li et al, 2021 ). The virulence plasmid described earlier such as the pLVPK and pK2044 lacked genes coding for antimicrobial resistance and typically belonged to IncHI1B ( Chen et al, 2004 ).…”

“…In addition, reports of fusion/mosaic plasmids that carry two replicons such as IncHI1B–IncFIB and IncFIIK–IncFIBK are emerging, which code for antimicrobial resistance determinants as well as virulence genes ( Lam et al, 2019 ; Turton et al, 2019 ). Furthermore, HvKp is no longer confined to selected clones but is reported among regional endemic clones such as ST11 in China and ST147 in Europe ( Turton et al, 2019 ; Li et al, 2021 ). Hence, the threat of these superbugs is increasing, and this pathotype is evolving at a tremendous pace.…”

Lytic Bacteriophages against Mutidrug-Resistant Klebsiella pneumoniae: Development of an Effective Phage-based Approach to Combat Multidrug Resistance

“…K. pneumoniae is prominent in the WHO bacterial priority pathogen list and as such has been the subject of several phage studies. This is especially for well-established lineages of Klebsiella considered high-risk clones (e.g., ST11) because of high antimicrobial resistance rates and virulence 22,23 The 14 fully characterised bacteriophages in this study were of diverse sequence and morphology and were members of five different families (Figure 1). Viruses belonging to Autographiviridae had the best activity against our Klebsiella collection (Figure 3).…”

Clinical and Molecular Characteristics of Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae Isolates in a Tertiary Hospital in Shanghai, China

“…This is consistent with the increasing trend of CR-hvKP literature reports. Since the first description of CR-hvKP by Zhang et al in 2015, 10 more and more CR-hvKP literature has been reported, [17][18][19][20] mainly in the Asia-Pacific region, especially in China. CR-hvKP is a super bacterium with hypervirulence and multidrug resistance, which has great harm to people's health and high mortality rate.…”