TY - UNPB
T1 - Group 2 and 3 ABC-transporter dependent capsular K-loci contribute significantly to variation in the invasive potential of Escherichia coli
AU - Gladstone, Rebecca A.
AU - Pesonen, Maiju
AU - Pöntinen, Anna K.
AU - Mäklin, Tommi
AU - MacAlasdair, Neil
AU - Thorpe, Harry
AU - Shao, Yan
AU - Mallawaarachchi, Sudaraka
AU - Arredondo-Alonso, Sergio
AU - Parcell, Benjamin J.
AU - Turnbull, Jake David
AU - Tonkin-Hill, Gerry
AU - Johnsen, Pål J.
AU - Samuelsen, Ørjan
AU - Thomson, Nicholas R.
AU - Lawley, Trevor
AU - Corander, Jukka
PY - 2024/11/23
Y1 - 2024/11/23
N2 - The major opportunistic pathogen Escherichia coli is the largest cause of antimicrobial resistance (AMR) associated infections and deaths globally. Considerable antigenic diversity has been documented in Extra-intestinal pathogenic E. coli (ExPEC). Still, the need for systematic genomic surveys of asymptomatic colonisation and invasive disease has precluded the quantification of K-type invasive potential across different ExPEC lineages. We assembled and curated an in-silico capsular typing database for group 2 and group 3 K-loci from >20,000 genomes and applied it to paired carriage and disease cohorts to investigate K-type epidemiology. The most virulent circulating capsules have estimated odds ratios of >10 for being found in bloodstream infections versus carriage. The invasive potential differed markedly between lineages, and subclades of the global multi-drug resistant ST131, which displayed limited O and H antigens but substantial K-type diversity. We also discovered that insertion sequence elements contribute to the evolutionary dynamics of group 2 and group 3 K-loci by importing new capsular genes. Furthermore, the level of capsule diversity was positively correlated with more recombinogenic lineages that could adapt their antigenic repertoire faster. Our investigation highlights several K-types and lineages that contribute disproportionately to invasive ExPEC disease, which are associated with high levels of AMR. These results have significant translational potential, including improved ExPEC diagnostics, personalised therapy options, and the ability to build predictive regional risk maps by combining genomic surveys with demographic and patient frailty data.
AB - The major opportunistic pathogen Escherichia coli is the largest cause of antimicrobial resistance (AMR) associated infections and deaths globally. Considerable antigenic diversity has been documented in Extra-intestinal pathogenic E. coli (ExPEC). Still, the need for systematic genomic surveys of asymptomatic colonisation and invasive disease has precluded the quantification of K-type invasive potential across different ExPEC lineages. We assembled and curated an in-silico capsular typing database for group 2 and group 3 K-loci from >20,000 genomes and applied it to paired carriage and disease cohorts to investigate K-type epidemiology. The most virulent circulating capsules have estimated odds ratios of >10 for being found in bloodstream infections versus carriage. The invasive potential differed markedly between lineages, and subclades of the global multi-drug resistant ST131, which displayed limited O and H antigens but substantial K-type diversity. We also discovered that insertion sequence elements contribute to the evolutionary dynamics of group 2 and group 3 K-loci by importing new capsular genes. Furthermore, the level of capsule diversity was positively correlated with more recombinogenic lineages that could adapt their antigenic repertoire faster. Our investigation highlights several K-types and lineages that contribute disproportionately to invasive ExPEC disease, which are associated with high levels of AMR. These results have significant translational potential, including improved ExPEC diagnostics, personalised therapy options, and the ability to build predictive regional risk maps by combining genomic surveys with demographic and patient frailty data.
U2 - 10.1101/2024.11.22.24317484
DO - 10.1101/2024.11.22.24317484
M3 - Preprint
BT - Group 2 and 3 ABC-transporter dependent capsular K-loci contribute significantly to variation in the invasive potential of Escherichia coli
PB - medRxiv
ER -