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This doctoral scholarship investigates why a certain type of Salmonella, called S. Kentucky, is particularly successful in acquiring antibiotic resistance. By looking into detail to its genome, and studying the movements of particular genetic loci using fluorescent microscopy in the laboratory of Prof. Aertsen (KULeuven), we hope to learn more on which factors are important in the spread of resistance among bacteria.
Salmonella enterica serovar Kentucky (S. Kentucky) is a commonly causes gastroenteritis in humans. It is one of most notorious Salmonella serotypes, as it is strongly associated with antimicrobial resistance (AMR). Ciprofloxacin-resistant S. Kentucky (CIPR S. Kentucky) belongs to a single sequence type (ST198), which acquired of a variant of the Salmonella genomic island 1 (SGI1) conferring resistance to first-line antimicrobials (β-lactams, aminoglycosides, sulphonamides, tetracyclines). The multidrug resistant (MDR) clone has since then also accumulated various substitution mutations in the quinolone resistance determining regions (QRDR) of DNA gyrase (gyrA) and DNA topoisomerase (parC), such that most strains carry three QRDR mutations which together confer full resistance to ciprofloxacin as well. The analysis of the genetic relationship with related bacteria, indicated that this clone first emerged in Egypt ca. 1989, before disseminating into Northern, Southern and Western Africa, and then further to the Middle East, Asia and Europe.
Most recently, the situation has worsened, as ECDC launched an Urgent Inquiry (UI-464) on a CIPR S. Kentucky ST198 strain carrying a chromosomally integrated blaCTX-M-14b gene encoding for cephalosporin resistance. The insertion event was traced back to Malta, but the strain has already spread to Belgium, UK, The Netherlands and five other EU countries. To date, this clone is only reported in humans, as opposed to (for example) the CipS S. Kentucky ST152 clone widely found in poultry in the USA but rarely reported in humans.
In this project, we investigate
- what explains the evolutionary success of the multidrug resistant S. Kentucky ST198 clone,
- what is the mechanisms of the integration (and potential further transfer) of the ESBL gene in its chromosome, and
- if there are genetic determinants of different human-animal host ranges in epidemic S. Kentucky ST198 and ST152