Epigenetics of Antimicrobial Resistance in Gram-Negative Bacteria

Resistance to antimicrobials is a well-known phenomenon leading to difficulties in the treatment of infectious diseases. The genetic determinants of such resistance are in general well understood: plasmids, transposons, insertion sequences and integrons are the most frequently related genetic elements. The word epigenetics refers to changes in the phenotype or in the gene expression caused by mechanisms other than underlying DNA sequence. In some cases these changes can remain for generations. Serratia marcescens is an enterobacterium characterized by its natural (intrinsic) resistance to most antibiotics. It is also a relevant opportunistic pathogen which has been involved in several pathologies such as urinary tract infections, prostheses infections, cellulitis, bacteremia and others. P. aeruginosa is a Gram-negative bacterium considered one of the major nosocomial pathogens worldwide. It causes several infections such as wound and burn infections as well as respiratory tract infections mostly affecting cystic fibrosis patients. An increasing prevalence of infections caused by multidrug-resistant (MDR) isolates has been reported in many countries and is actually a cause of concern. Both, P. aeruginosa and S. marcescens are relevant nosocomial pathogens. Some of the classic antimicrobials used to treat these pathogens are out-of-date and several of the new drugs available have already become targets for bacterial mechanism of resistance. Environmental conditions exert high pressure not only in the selection of genes encoding resistance to antibiotics or integron fixation in bacterial genomes or plasmids and other mobile elements transmission, but also in the expression of these potentialities that leads to resistance. Thus the role of epigenetics remains to be investigated. In addition it is well known that bacteria causing infections are naturally forming part of biofilms instead the planktonic way of life normally assumed to be in laboratory conditions. The aim of this thesis was the study of unconventional ...