Antibiotic resistance mechanisms in Enterobacteriaceae

Enterobacteriaceae species are important human pathogens while increasing number of antibiotic resistant strains are detected worldwide. The most common antibiotic resistance in Enterobacteriaceae is observed against beta-lactams, fluoroquinolones, aminoglycosides while recently resistance to polymyxins has also appeared. Beta-lactam resistance is mainly conferred by beta-lactamases, capable to hydrolyze beta-lactam antibiotics. The most important beta-lactamases are the cephalosporinases for example extended-spectrum beta-lactamases (ESBLs) and the carbapenemases for example metallo-beta-lactamases (MBLs), Klebsiella pneumoniae carbapenemases (KPCs) and oxacillinase OXA-48 enzymes. Other resistance mechanisms against beta-lactams are the outer membran permeability change and efflux pumps. Fluoroquinolone resistance is caused by aminoacid changes in gyrase and topoisomerase IV enzymes. However, recent studies confirmed the importance of plasmid-mediated quinolone resistance mechanisms including Qnr determinants, aminoglycoside-acetyltransferase(6’)-Ib-cr enzyme and QepA, OqxAB efflux pumps. Aminoglycoside resistance is mainly explained by modifying enzymes inactivating the antibiotic by acetylation, by adenylation or by phosphorilation. Resistance to polymyxins develops by the modification of the target molecule, notably the addition of 4-amino-4-deoxy-larabinopyranose on the lipid A component of lipopolysaccharide. The genetic background of resistance mechanisms is diverse since they can be present on chromosomes, plasmids, integrons and transposones. This chapter gives an overview of beta-lactam, fluoroquinolone, aminoglycoside and polymyxin resistance mechanisms in Enterobacteriaceae.