Genomic epidemiology of emerging ESBL-producing Salmonella Kentucky bla _CTX-M-14b in Europe

Abstract

Global dissemination of ciprofloxacin-resistant Salmonella Kentucky has been observed over the past decades. In recent years, there have been reports of extended-spectrum β-lactamase (ESBL) producing S . Kentucky. Routine surveillance at the European Centre for Disease Prevention and Control (ECDC) detected cases with a ciprofloxacin-resistant S . Kentucky with the ESBL-gene bla CTX-M-14b . Ensuing research identified 78 cases in 2013–2018 in eight European countries. Compared to other S . Kentucky and non-typhoidal Salmonella infections, reported to the European Surveillance System, these cases were more likely to be elderly and to present urinary-tract infections. Bayesian time-scaled phylogeny on whole genome sequences of isolates from these cases and supplementary isolates from public sequence databases was used to infer the origin and spread of this clone. We dated the origin of the bla CTX-M-14b clone to approximately 2005 in Northern Africa, most likely in Egypt. The geographic origin predicted by the phylogenetic analysis is consistent with the patients’ travel history. Next to multiple introductions of the clone to Europe from Egypt, our analysis suggests that in some parts of Europe the clone might have formed a stable population, from which further spread has occurred. Comparative genomics indicated that the bla CTX-M-14b gene is present on the bacterial chromosome, within the type VI secretion system region. The bla CTX-M-14b gene is integrated downstream of the hcp1 gene, on a 2854 bp plasmid fragment containing also IS Ecp1 . This is the first report of a chromosomally integrated CTX-M gene in Salmonella spp. in Europe, previous studies having identified similar genes only on plasmids.

The European Union Summary Report on Antimicrobial Resistance in zoonotic and indicator bacteria from humans, animals and food in 2018/2019

“…Acquisition of SGI1 and plasmids, as well as mutations in the QRDR, were the only genetic features found during this study to explain the global epidemiological success of the MDR S. Kentucky ST198 lineage which is highly resistant to ciprofloxacin. Coipan et al (2020) describe how a clone of this lineage, with an ESBL-gene (bla CTX-M-14b ) incorporated on the chromosome, has emerged in Europe. In contrast to plasmid-mediated resistance, chromosomal-mediated resistance is most likely to be maintained also without antibiotic pressure, especially if it incurs no fitness cost for the bacteria.…”

“…The proportion of S. Kentucky with an ESBL phenotype decreased from 20.3% in 2017 to 5.6% in 2019, with four countries (Germany, France, Malta and the Netherlands) reporting presumptive ESBL-producing S. Kentucky in 2019. The introduction and spread of S. Kentucky with bla CTX-M-14b in Europe has recently been described by Coipan et al (2020). During this study, conducted over the period 2013-2018, 78 human cases of S. Kentucky harbouring the bla CTX-M-14b gene (as well as displaying gyrA and parC mutations associated with ciprofloxacin resistance) were identified in eight European countries (comprising the United Kingdom, Malta, the Netherlands, Germany, Belgium, Denmark, Norway and Ireland).…”

Third generation cephalosporin resistance in clinical non-typhoidal Salmonella enterica in Germany and emergence of bla CTX-M-harbouring pESI plasmids

“…Interestingly, ESBL production correlates with certain serovars in S. enterica. Among serovars found in human infections, ESBL genes have been more frequently detected in S. Typhimurium, S. Infantis and S. Kentucky than in S. Enteritidis [5,14]. Furthermore, recent analyses on ESBL-producing S. Infantis from broiler chickens, broiler meat, and humans revealed a clonal lineage harbouring an especially successful conjugative pESI-like plasmid [15].…”

Development of an NGS-Based Workflow for Improved Monitoring of Circulating Plasmids in Support of Risk Assessment of Antimicrobial Resistance Gene Dissemination

“…With the hybrid assemblies obtained with the workflow, it was determined that in the Belgian S. Kentucky isolates, the ESBL genes were present on both the chromosome and on plasmids and that there was also a likely exchange by a transposase of a 2850 bp region between the chromosome and a plasmid of different isolates. The results of our workflow on the Belgian isolates, and especially of the plasmid reconstruction, were put into epidemiological context of the other European Salmonella Kentucky ESBL-positive isolates by Coipan et al [83]. They found that this 2850 bp fragment was present in the chromosome and plasmids of other S. Kentucky isolates [83].…”

“…The results of our workflow on the Belgian isolates, and especially of the plasmid reconstruction, were put into epidemiological context of the other European Salmonella Kentucky ESBL-positive isolates by Coipan et al [83]. They found that this 2850 bp fragment was present in the chromosome and plasmids of other S. Kentucky isolates [83]. The exchanged fragment is very similar to that on the chromosome of an S. Kentucky isolated from poultry in China [64]; however, the exact sequence reported in the Chinese study is not yet available in public databases to make the full comparison.…”