Biology subjects

Fordham, S. M. E.

Publications and source records attributed to Fordham, S. M. E..

5 recordsLinked to original sources

bioRxiv2026

Companion animals harbour globally circulating human-associated Klebsiella pneumoniae lineages and high-risk antimicrobial resistance clones

Companion animals are increasingly recognised within One Health antimicrobial-resistance (AMR) surveillance, yet the global genomic structure of dog- and cat-associated Klebsiella pneumoniae remains poorly defined. We assembled a global dataset of 712 domestic dog- and cat-derived K. pneumoniae genomes to define lineage diversity, AMR burden, host-associated patterns and overlap with human-associated populations. Companion-animal isolates comprised 263 sequence types (STs), but recurrent high-risk lineages, including ST307, ST11, ST15 and ST147, were prominent. Among 706 isolates from 25 countries, extended-spectrum {beta}-lactamase (ESBL) and carbapenemase genes were widely distributed, detected in 303 (42.9%) and 98 (13.9%) isolates, respectively. Cat-derived isolates showed higher multidrug-resistance (MDR) prevalence than dog-derived isolates; 80.0% versus 56.3%, partly reflecting enrichment of epidemic clones, especially ST147. MDR was not confined to infection-associated samples, indicating that colonisation may represent an important reservoir state. Comparison with 38,106 human-associated K. pneumoniae isolates revealed extensive ST overlap, with 71.1% of companion-animal STs and 87.2% of companion-animal isolates belonging to STs also detected in humans. Focused recombination-filtered phylogenomics of ST147 identified a recent host-spanning MDR sub-lineage linking cat-, dog- and human-associated genomes. Together, these findings show that domestic dogs and cats are not epidemiologically separate from the wider K. pneumoniae AMR landscape, but harbour globally circulating human-associated lineages and high-risk AMR clones.

microbiology↗

bioRxiv2024

The presence of an ESBL-encoding plasmid reported during a Klebsiella pneumoniae nosocomial outbreak in the United Kingdom

The presence of extended-spectrum {beta}-lactamase (ESBL) encoding plasmids in bacteria contributes towards rising resistance rates, mortality and healthcare costs in clinical settings. An EBSL-encoding plasmid, pESBL-PH was identified during a nosocomial outbreak of Klebsiella pneumoniae ST628 at a United Kingdom general district hospital in 2018. A plasmid from the earliest 2018 K. pneumoniae strain discovered during the outbreak was assembled using both Oxford nanopore long reads and illumina short reads, yielding a fully closed plasmid, pESBL-PH-2018. pESBL-PH-2018 was queried against the complete NCBI RefSeq Plasmid Database, comprising 93,823 plasmids, downloaded on July 16, 2024. To identify structurally similar plasmids, strict thresholds were applied: both a shared hash ratio > 0.9 and a mash similarity [≥] 0.98. This returned 61 plasmids belonging to 13 unique sequence types (STs) hosts. The plasmids were detected in 13 unique countries, dating from 2012-2023, associated with a range of infections including bacteremia. Low numbers of single nucleotide polymorphisms (SNPs) were identified between pESBL-PH-2018 and query plasmids, further confirming their relatedness. The AMR region of the plasmids varied; interestingly IS26 mediated-tandem amplification of resistance genes, including the ESBL blaCTX-M-15 was identified in two independent strains raising their copy number to three. Furthermore, the genomic background of strains carrying a pESBL-PH-2018-like plasmid were analyzed, revealing truncation of the chromosomal ompK36 porin gene and carbapenemase resistance gene carriage on accessory plasmids in 17.85% and 26.78% of strains with a complete chromosome available. This analysis reveals the widespread dissemination of an ESBL-encoding plasmid in a background of resistance-encoding strains, requiring active surveillance.

microbiology↗

bioRxiv2024

KlebPhaCol: A community-driven resource for Klebsiella research identified a novel gut phage order associated with the human gut

The growing threat of multidrug-resistant Klebsiella pneumoniae, coupled with its role in gut colonisation, has intensified the search for new treatments, including bacteriophage therapy. Despite increasing documentation of Klebsiella-targeting phages, clinical applications remain limited, with key phage-bacteria interactions still poorly understood. A major obstacle is fragmented access to well-characterised phage-bacteria pairings, restricting the collective advancement of therapeutic and mechanistic insights. To address this gap, we created the Klebsiella Phage Collection (KlebPhaCol), an open-source resource comprising 53 phages and 74 Klebsiella isolates, all fully characterised. These phages span five families - including a novel order, Felixvirales, associated with the human gut - and target 27 sequence types (including ST258, ST11, ST14) and 28 capsular-locus types (including KL1 and KL2), across six Klebsiella species. Freely accessible at www.klebphacol.org, KlebPhaCol invites the scientific community to both use and contribute to this resource, fostering collaborative research and a deeper understanding of Klebsiella-phage interactions beyond therapeutic use.

microbiology↗

bioRxiv2022

Bioinformatic analyses of plasmid resistome changes in pOXA-48

Infections caused by carbapenem resistant Enterobacteriales (CPE) represent a significant threat in clinical settings. blaOXA-48 is one of the most frequent carbapenemase genes among Enterobacteriales. The blaOXA-48 is typically encoded on the prototypical IncL conjugative pOXA-48 plasmid. The pOXA-48 plasmid encodes only the blaOXA-48 resistance gene. However, aminoglycoside and extended spectrum {beta}-lactamase (ESBL) resistance genes have also been detected on the same pOXA-48 plasmid backbone. These pOXA-48 plasmids encoding additional antimicrobial resistance (AMR) genes have been associated with both poor patient outcome and increased minimal inhibitory concentrations (MICs) to antibiotics including broad-spectrum cephalosporins. The blaOXA-48 gene was sourced from the pOXA-48 reference plasmid and set as a query using the BLASTn tool. Non-duplicate blaOXA-48 containing plasmids were downloaded, incompatibility typed and annotated for resistance genes using ResFinder 4.0. Bioinformatic analyses identified three distinct variants of the pOXA-48 plasmid encoding 4, 5, and 6 antimicrobial resistance genes. All plasmids encoded the ESBL blaCTX-M-14b, blaOXA-48 and either 2, 3 or 4 aminoglycoside resistance genes, in addition to conjugative transfer machinery. Plasmid variants 1 and 3 encoded aminoglycoside genes bracketed between IS26 and ISEc63 insertion elements, forming a potential transposon. The potential transposon structure had resemblance to the Tn5393 transposon (accession: M96392), including both aph(3)-Ib, aph(6)-Id genes, and a Tn3 resolvase. The IS element ISEcp1 lies upstream of blaCTX-M-14b. All three plasmid variants appear related. Notably, all pOXA-48 plasmid variants were identified in multiple countries. In particular, variant 1 including 6 AMR genes was detected in 7 unique countries. Plasmids encoding additional AMR genes were associated with clinical/surveillance samples suggesting antibiotic pressure in clinical settings may promote changes in the resistome of pOXA-48. Acquisition of pOXA-48 resistant plasmids carrying additional AMR genes beyond blaOXA-48 can change the resistome of susceptible isolates in a single-step, rendering previously susceptible strains refractory to almost all available treatment options.

microbiology↗

bioRxiv2021

Plasmids as donors of Insertion Sequence elements mediating colistin resistance in Klebsiella pneumoniae

Colistin is a last resort antibiotic for the treatment of carbapenemase producing Klebsiella pneumoniae (CRKP). In line with rising colistin use worldwide, colistin resistant Klebsiella pneumoniae (K. pneumoniae) isolates have emerged. The disruption of mgrB by insertion sequences (ISs) has been widely reported worldwide representing a mechanism mediating colistin resistance. Evidence suggests plasmids encode mobilizable IS elements which preferentially integrate into the mgrB gene in K. pneumoniae causing gene inactivation and colistin resistance. Recognised IS elements targeting mgrB include ISL3 (ISKpn25), IS5 (ISKpn26), ISKpn14 and IS903B-like elements. K. pneumoniae represents the single largest species carrying plasmids encoding these IS elements. For IS presence among species, 1000 BLASTn hits were downloaded and filtered for plasmids. Additionally, the top 120 BLASTn non-duplicate circularised plasmid contig hits for each IS element were typed for incompatibility (Inc) group and carbapenemase gene presence. IS903B was found in 28 unique Inc groups, while ISKpn25 was largely carried by IncFIB(pQil) plasmids. ISKpn26 and ISKpn14 were most often found associated with IncFII(pHN7A8) plasmids. Of the 34 unique countries which contained any of the IS elements, ISKpn25 was identified from 26. ISKpn26, ISKpn14, and IS903B insertion sequences were identified from 89.3%, 44.9% and 23.9% plasmid samples from China. Plasmids carrying ISKpn25, ISKpn14, and ISKpn26 IS elements are 12.18, 27.0, and 44.43 times more likely to carry carbapenemase genes relative to plasmids carrying the IS element IS903B. Moreover, plasmids carrying ISKpn26, ISKpn25, and ISKpn14 were 6.10, 28.82, and 31.47 times more likely to be sourced from a clinical environmental setting than the environment relative to IS903B IS harboring plasmid. ISKpn25 present on IncFIB(pQil) sourced from clinical settings is established across multiple countries, while ISKpn26, ISKpn14, and IS903B appear most often in China. High carbapenemase presence in tandem with IS elements may help promote an extensively drug resistant profile in K. pneumoniae limiting already narrow therapeutic treatment options.

microbiology↗