Convergence of virulence and MDR in a single plasmid vector in MDR Klebsiella pneumoniae ST15

Abstract

Background MDR and hypervirulence (hv) are typically observed in separate Klebsiella pneumoniae populations. However, convergent strains with both properties have been documented and potentially pose a high risk to public health in the form of invasive infections with limited treatment options. Objectives Our aim was to characterize the genetic determinants of virulence and antimicrobial resistance (AMR) in two ESBL-producing K. pneumoniae isolates belonging to the international MDR clone ST15. Methods The complete genome sequences of both isolates, including their plasmids, were resolved using Illumina and Oxford Nanopore sequencing. Results Both isolates carried large mosaic plasmids in which AMR and virulence loci have converged within the same vector. These closely related mosaic hv-MDR plasmids include sequences typical of the K. pneumoniae virulence plasmid 1 (KpVP-1; including aerobactin synthesis locus iuc ) fused with sequences typical of IncFII K conjugative AMR plasmids. One hv-MDR plasmid carried three MDR elements encoding the ESBL gene bla CTX-M-15 and seven other AMR genes ( bla TEM , aac3'-IIa , dfrA1 , satA2 , bla SHV , sul1 and aadA1 ) . The other carried remnants of these elements encoding bla TEM and aac3'-IIa , and bla CTX-M-15 was located in a second plasmid in this isolate. The two isolates originated from patients hospitalized in Norway but have epidemiological and genomic links to Romania. Conclusions The presence of both virulence and AMR determinants on a single vector enables simultaneous transfer in a single event and potentially rapid emergence of hv-MDR K. pneumoniae clones. This highlights the importance of monitoring for such convergence events with stringent genomic surveillance.

The Small Protein RmpD Drives Hypermucoviscosity in Klebsiella pneumoniae

“…To date, HMV has primarily been associated with hv K1 and K2 strains, but more than 130 capsule types of K. pneumoniae have been identified ( 44 ). Of significant concern is the number of recent reports of strains with both multidrug resistance and hv-associated genes, including rmpA (and quite likely rmpD and rmpC ) ( 18 – 23 ). These strains are genetically quite distinct (including capsule type) from the hvKp that have been circulating, and it is not known to what degree acquisition of the rmpADC locus will impact HMV and virulence of these strains.…”

“…That these genetic entities can be horizontally transferred suggests there is an increased risk of strains acquiring both hypervirulence and multidrug resistance ( 16 , 17 ). Alarmingly, there have been recent reports of extensively resistant hypervirulent K. pneumoniae ( 18 , 19 ), and multiple strains where both hv-associated genes and antimicrobial resistance genes were present on the same mobile vector ( 20 – 23 ). These reports of convergence of hypervirulence and antimicrobial resistance in the same strain have heightened the need to better understand how hypervirulence genes interface with a strain’s genetic background to confer hypervirulent phenotypes.…”

Vertical and Horizontal Transmission of ESBL Plasmid from Escherichia coli O104:H4

“…Virulence plasmids can be fully or partially responsible for the pathogenicity of the host pathogen (e.g., pINV of enteroinvasive E. coli and pSLT of Salmonella enterica serovar typhimurium, respectively), while MDR plasmids can confer on host cells a great fitness advantage when they are challenged by corresponding antibiotics. Note that composite plasmids carrying both virulence and MDR genes are also emerging [ 40 , 41 ]. In virulence plasmids, the presence of active partitioning, PSK and multimer resolution mechanisms ensures their prevalence [ 42 ].…”

Genomic and Proteomic Characterization of the Extended-Spectrum β-Lactamase (ESBL)-Producing Escherichia coli Strain CCUG 73778: A Virulent, Nosocomial Outbreak Strain

“…Firstly, pSUH-1 exhibited four matches, covering more than 95% of the sequence with identities greater than 99.9%, with plasmids present in clinical E. coli isolates from Sweden (CP023845.1), South Korea (CP024831.1 and CP024816.1) and the USA (CP025708.1). Secondly, pSUH-2 exhibited two matches, covering more than 96% of the sequence, with a plasmid harbored in the multidrug resistant strain Klebsiella pneumoniae strain KP_112126 [72] and with plasmids harbored in bla CTX-M-15 producing E. coli strains isolated in Canada [73], with identities greater than 99%, in both cases. The most remarkable part of pSUH-2 is a sequence between positions 43,211 and 59,126, containing several regions flanked by transposases.…”