Phylogenomics of globally spread Clonal Groups 14 and 15 of Klebsiella pneumoniae

Abstract

The increasing worldwide spread of multidrug-resistant (MDR) Kp is largely driven by high-risk sublineages, some of them well-characterised such as Clonal Group (CG) 258, CG147 or CG307. MDR Kp Sequence-Type (ST) 14 and ST15 have been described worldwide causing frequent outbreaks of CTX-M-15 and/or carbapenemase producers. However, their phylogeny, population structure and global dynamics remain unclear. Here, we clarify the phylogenetic structure and evolvability of CG14 and CG15 Kp by analysing the CG14 and CG15 genomes available in public databases (n=481, November 2019) and de novo sequences representing main sublineages circulating in Portugal (n=9). Deduplicated genomes (n=235) were used to infer temporal phylogenetic evolution and to compare their capsular locus (KL), resistome, virulome and plasmidome using high-resolution tools. Phylogenetic analysis supported independent evolution of CG14 and CG15 within two distinct clades and 4 main subclades which are mainly defined according to the KL and the accessory genome. Within CG14, two large monophyletic subclades, KL16 (14%) and KL2 (86%), presumptively emerged around 1937 and 1942, respectively. Sixty-five percent of CG14 carried genes encoding ESBL, AmpC and/or carbapenemases and, remarkably, they were mainly observed in the KL2 subclade. The CG15 clade was segregated in two major subclades. One was represented by KL24 (42%) and KL112 (36%), the latter one diverging from KL24 around 1981, and the other comprised KL19 and other KL-types (16%). Of note, most CG15 genomes contained genes encoding ESBL, AmpC and/or carbapenemases (n=148, 87%) and displayed a characteristic set of mutations in regions encoding quinolone resistance (QRDR, GyrA83F/GyrA87A/ParC80I). Plasmidome analysis revealed 2463 plasmids grouped in 27 predominant plasmid groups (PG) with a high degree of recombination, including particularly pervasive F-type (n=10) and Col (n=10) plasmids. Whereas blaCTX-M-15 was linked to a high diversity of mosaic plasmids, other ARGs were confined to particular plasmids (e.g. blaOXA-48-IncL; blaCMY/TEM-24-IncC). This study firstly demonstrates an independent evolutionary trajectory for CG15 and CG14, and suggests how the acquisition of specific KL, QRDR mutations (CG15) and ARGs in highly recombinant plasmids could have shaped the expansion and diversification of particular subclades (CG14-KL2, CG15-KL24/KL112).

Emergence of NDM-producing Enterobacterales infections in companion animals from Argentina

“…It could be explained by the acquisition of extra plasmid/s coding for resistance to these drugs by this strain. ST15 CTX-M-1/15 K. pneumoniae lineage was previously reported in companion animals and humans in Portugal [22] and among other countries [23]. K. pneumoniae ST15 clone was also reported to produce different carbapenemases, however bla OXA-48 was the common [23,24].…”

Decoding Klebsiella pneumoniae in poultry chain: unveiling genetic landscape, antibiotic resistance, and biocide tolerance in non-clinical reservoirs

“…In our comparative genomic analysis using WGS, we identified closely related MDR K. pneumoniae lineages such as ST15-KL19, ST11-KL111, ST280-KL23, and ST1997-KL28 shared between poultry and human clinical isolates, even when applying strict criteria of less than 21 SNPs (David et al, 2019). Additionally, certain poultry strains shared a substantial repertoire of accessory genes, including fluoroquinolone resistance mutations and/or virulence genes with clinically relevant human clones (e.g., ST15, ST147, ST307) identified in previous studies (Peirano et al, 2020;Rodrigues et al, 2022Rodrigues et al, , 2023. This data strengthens the argument for the possible transmission of these strains from food animals to humans (Büdel et al, 2020;Rodrigues et al, 2022;Thorpe et al, 2022;Crippa et al, 2023;Kaspersen et al, 2023;Zou et al, 2023), solidifying poultry's position as both a reservoir and source of globally dispersed, clinically relevant K. pneumoniae lineages (Mourão et al, 2023).…”

From farm to fork: persistence of clinically-relevant multidrug-resistant and copper-tolerantKlebsiella pneumoniaelong after colistin withdrawal in poultry production

“…It is of remark that metal tolerance operons (pco+sil) were mainly located in multireplicon F-type (FIIK+FIBK) plasmids carrying genes encoding resistance to several classes of antibiotics, including the critical extended-spectrum cephalosporins and/or fluoroquinolones, supporting the potential for diverse co-selection events (67,68). These mosaic F-type plasmids are common in K. pneumoniae populations from different sources (68)(69)(70)(71)(72)(73), suggesting a major role in both dissemination and persistence of antibiotic resistance and metal tolerance genes, and K. pneumoniae adaptation to different niches. Besides, the similarity between plasmid backbones .…”

“…The copyright holder for this preprint this version posted April 3, 2023. ; https://doi.org/10.1101/2023.04.03.535403 doi: bioRxiv preprint identified in poultry isolates with those described in K. pneumoniae collections from humans (Table S3, Table S4) (72) suggests a common pool of shared plasmids between humans and eventually different animal species (70) that deserves to be further explored with comprehensive comparative plasmidome analysis. This is the first study tracking K. pneumoniae throughout the whole poultry production chain, enabling the identification of multiple transmission routes in flocks and the farm environment.…”