KENTUCKY: Exploring the evolutionary success of the antibiotic resistant Salmonella Kentucky ST198
Salmonella enterica serovar Kentucky (S. Kentucky) is a common causative agent of 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 (b-lactams, aminoglycosides, sulphonamides, tetracyclines). The 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. Phylogeographic analysis indicates 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.
The main reservoir of S. Kentucky is poultry, and domestic poultry has played an important role in its global spread (most recently in South Asia and Europe). Ciprofloxacin resistance is rare in Salmonella, and is hypothesised to be linked to strong selective pressure exerted by fluoroquinolone use in poultry.
In addition to CIPR, S. Kentucky is able to gain additional antibiotic resistance determinants through the acquisition of locally circulating plasmid-borne ESBL, AmpC and/or carbapenemase genes. Additionally, the geographic distribution of ciprofloxacin-resistant (CIPR) S. Kentucky ST198 overlaps with other highly drug resistant Enterobacteriaceae carrying plasmid-borne ESBL, AmpC and/or carbapenemase genes, leading to predictions that highly-drug resistant Kentucky ST198 strains are likely to become more frequent in the near future due to novel plasmid acquisitions.
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 will investigate (i) what explains the evolutionary success of the multidrug resistant S. Kentucky ST198 clone, (ii) what is the mechanisms of the integration (and potential further transfer) of the ESBL gene in its chromosome, and (iii) Are there genetic determinants of different human-animal host ranges in epidemic S. Kentucky ST198 and ST152?
Jasper van der Peet
About me: Hi everyone! My name is Jasper and I am 26 years old. I fell in love with microbiology during my bachelor’s programme of biomedical sciences in Amsterdam, the Netherlands. Thereafter I moved to Nijmegen, NL, for a master’s degree focusing on microbiology. I have enjoyed many internships at various institutes within the Netherlands and the US where I explored molecular microbiological research topics and greatly expanded my laboratory skill set. I am passionate about molecular biology, especially when used to face today’s societal challenges, such as antimicrobial resistance. Aside from science I like to socialise, make music, dance, sing etc…
What motivated me to do a PhD: I have always been drawn towards health-related science and I now have the privilege of making a career out of that passion. The project ties in well with my fascination for antimicrobial resistance mechanisms and I am keen on doing molecular research on a bacterial strain of direct clinical value. I can apply my previous experience in a setting that is new and exciting to me and I am looking forward to delve into the finer details of the bacterial strain I am working with. Thanks to the OHEJP I can contribute to an important effort to improve public health.