I-complex plasmids – a story about incompatibility and host adaptation.

Abstract

Antimicrobial resistance (AMR) is a growing problem worldwide. This is mainly the result of the presence of resistance genes in bacteria. When these genes are located in small pieces of DNA, so called plasmids, they can easily spread between bacteria. This thesis gives an overview the different types of plasmids, all with their different resistance genes, and their presence around the globe. Bacteria may contain a number of different plasmids in a single cell. whether any of these plasmids can be stably maintained depends on several factors. One of these factors is called incompatibility, which is the inability of plasmids to be maintained in one cell. Based on this incompatibility plasmids can be categorized in 40 different “Inc” groups, a biological phenomenon that was long used as a typing system to study epidemiology. This thesis focusses on the members of the “I-complex” incompatibility group, found in Enterobacteriaceae and frequently associated with important resistance gene classes such as the so-called Extended Spectrum Beta-lactamases (ESBLs). The I-complex includes IncI1α, IncI1γ, IncI2, IncK, IncB/O and IncZ plasmids. In this thesis the basis of their incompatibility is analysed and the results show that a single mutation (change in DNA) can determine if two plasmids are compatible or not. It concludes that IncB/O and IncZ plasmids, which were previously considered compatible and thus different plasmids, were actually incompatible and should be considered as highly similar. It also shows that the IncK plasmid group, which is an important carrier of resistance genes in human and poultry bacteria, consists of two compatible plasmid lineages, designated IncK1 and IncK2. Studies into the molecular effects of these plasmid types on the physiology of their host cell showed that IncK2 plasmids provide a fitness advantage at a higher environmental temperature which may have resulted in their predominance in poultry over IncK1, which is mostly found in mammals. Overall, the results presented in this thesis highlight the importance of plasmids in the spread of AMR, and it underlines the importance of understanding the plasmid compatibility and its adaptation to the bacterial or animal host.