Co-occurrence of Rapid Gene Gain and Loss in an Interhospital Outbreak of Carbapenem-Resistant Hypervirulent ST11-K64 Klebsiella pneumoniae

Abstract

We report an outbreak of carbapenemase-producing hypervirulent Klebsiella pneumoniae in two hospitals that undergo frequent patient transfers. Analysis of 11 completely assembled genomes showed that the bacteria were ST11-K64 strains. Moreover, 12 single nucleotide polymorphisms (SNPs) identified the strains as having originated from the same cluster, and were also indicative of the interhospital transmission of infection. Five plasmids were assembled in each of the strains. One plasmid carried several virulence genes, including the capsular polysaccharide regulators rmpA and rmpA2 . Two others carried antimicrobial-resistance genes, including one for carbapenem resistance, bla KPC–2 . Comparative genomic analysis indicated the occurrence of frequent and rapid gain and loss of genomic content along transmissions and the co-existence of progeny strains in the same ward. A 10-kbp fragment harboring antimicrobial resistance-conferring genes flanked by insert sequences was missing in a plasmid from strain KP20194c in patient 3, and this strain also likely subsequently infected patient 4. However, strains containing the 10-kbp fragment were also isolated from the ward environment at approximately the same time, and harbored different chromosome indels. Tn 1721 and multiple additional insert sequence-mediated transpositions were also seen. These results indicated that there is a rapid reshaping and diversification of the genomic pool of K. pneumoniae facilitated by mobile genetic elements, even a short time after outbreak onset. ST11-K64 CR-hvKP strains have the potential to become new significant superbugs and a threat to public health.

Isolation of a Ceftazidime-Avibactam-Resistant bla KPC-71 -Positive Klebsiella pneumoniae Clinical Isolate

“…WGS analysis revealed that K. pneumoniae HS645 belonged to sequence type 11 (ST11), and the following acquired resistance determinants were detected: resident bla KPC-71 , bla CTX-M-65 , bla SHV-12 , bla LAP-2 , and bla TEM-1B and resistance determinants for aminoglycosides ( aadA2b and rmtB ), fluoroquinolone ( qnrS1 ), tetracycline [ tet (A)], fosfomycin ( fosA ), and sulfonamide ( sul2 ) ( Table 1 ). Plasmid DNA sequencing localized bla KPC-71 on a plasmid about 60 kb in length, which contains the resistance genes on drug resistance gene islands similar to that reported in Hunan Province in China ( 11 ). Compared with KPC-2, KPC-71 has a mutation of Ser182dup.…”

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.…”

Emergence of KPC-2-Producing ST11-K64 Hypervirulent Klebsiella Pneumoniae for the Elderly in Intensive Care Unit: Antimicrobial Resistance, Molecular and Clinical Characteristics

“…Since all the strains were collected from the same ward ICU, we speculated clonal dissemination of KPC-2-producing ST11-K64 K. pneumoniae exited, and during the process of transmission, KPC-2-producing ST11-K64 K. pneumoniae acquire of a PLVKPlike virulence plasmid, leading to KPC-2-producing ST11-K64 CR-hvKP. ZHANG et al [42] also provided evidence that ST11-K64 K.pneuminiae may be a competent host strain for a hypervirulent plasmid. The emergence of KPC-2-producing ST11-K64 CR-hvKP might pose a serious challenge to the management of elderly patients infected with these strains in the future, as these strains contain both drug resistance and virulence genes and show higher resistance than CR-non-hvKP strains [32] .…”