Plasmid mediated quinolone resistance in Enterobacteriaceae

Abstract

This thesis describes the occurrence of Plasmid Mediated Quinolone Resistance (PMQR) in Salmonella and E. coli from The Netherlands and other European countries. Furthermore, the genetic background of these genes was characterized. Fluoroquinolones are widely used antibiotics in both human and veterinary medicine. Resistance to fluoroquinolones is considered to be a risk for human health and is mainly caused by chromosomal mutations in topoisomerase genes. Since 1998, different types of PMQR emerged encoded by different resistant genes: qnrA, qnrS, qnrB, qnrC, qnrD, aac(6’)-1b-cr, oqxAB and qepA. PMQR in Enterobacteriaceae results in reduced susceptibility to (fluoro)quinolones to levels below clinical breakpoints. However, PMQR is considered clinically relevant because it facilitates the acquisition of full quinolone resistance. In a national study, the earliest identified PMQR-positive Salmonella isolate in The Netherlands was a human qnrS1-positive S. Corvallis isolate obtained in 2003. Furthermore, eight different Salmonella serovars were found harbouring different PMQR genes (qnrS1, qnrB2 and qnrB19). Almost all isolates were of human origin. Further study revealed the presence of PMQR genes on different plasmid families, including IncN plasmids carrying qnrS1, qnrB2 or qnrB19. But also qnrS1 on ColE, IncR or incHI2 plasmids. The majority of these plasmids were self-transferable by conjugation. However, PMQR-genes were also present on smaller non-conjugative plasmids.More recently, a continuous low prevalence of PMQR-suspected Salmonella isolates was observed in The Netherlands with a slight tendency to increase. The earliest identified PMQR-positive E. coli in animals from The Netherlands was a qnrS1-carrying E. coli obtained from a broiler obtained in 2009. To date, the prevalence of PMQR-suspected E. coli in food-producing animals in The Netherlands is low and only observed in broilers and veal calves. A European study demonstrated a low prevalence of PMQR-positive Salmonella isolates, with qnrS1, qnrB19 and qnrB2 as the predominant PMQR-determinants identified. The rare qnrD1 was identified in eight different serovars from three different countries. This study demonstrated a wide spread of PMQR genes in Europe among Salmonella from different sources despite the low prevalence and it suggest poultry to be the main source for PMQR-determinants in Salmonella. Similar to Salmonella, the prevalence of PMQR was low in E. coli with predominant variant qnrS1 in isolates from poultry (Gallus gallus and turkeys). Antibiotic resistant bacteria can spread over great distances via travel of people or transport of animals, but also by the worldwide trade in food and feed. In this thesis two examples of import of multidrug resistant Enterobacteriaceae are discussed: PMQR-positive, multidrug resistant Salmonella obtained in humans originated from or had a travel history to the African continent and PMQR-positive, multidrug resistant Enterobacteriaceae identified on culinary herbs from Southeast Asia. Despite the strong reduction of fluoroquinolone usage in animals in The Netherlands, resistance is still high in commensal E. coli and Campylobacter spp. in some food-producing animal species. Although fluoroquinolone resistance is mainly caused by chromosomal mutations, PMQR complicates the development and spread of fluoroquinolone resistance which makes it important to include this in the surveillance.