Phenotypic Resistance to Antibiotics

Abstract

The development of antibiotic resistance is usually associated with genetic changes, either to the acquisition of resistance genes, or to mutations in elements relevant for the activity of the antibiotic. However, in some situations resistance can be achieved without any genetic alteration; this is called phenotypic resistance. Non-inherited resistance is associated to specific processes such as growth in biofilms, a stationary growth phase or persistence. These situations might occur during infection but they are not usually considered in classical susceptibility tests at the clinical microbiology laboratories. Recent work has also shown that the susceptibility to antibiotics is highly dependent on the bacterial metabolism and that global metabolic regulators can modulate this phenotype. This modulation includes situations in which bacteria can be more resistant or more susceptible to antibiotics. Understanding these processes will thus help in establishing novel therapeutic approaches based on the actual susceptibility shown by bacteria during infection, which might differ from that determined in the laboratory. In this review, we discuss different examples of phenotypic resistance and the mechanisms that regulate the crosstalk between bacterial metabolism and the susceptibility to antibiotics. Finally, information on strategies currently under development for diminishing the phenotypic resistance to antibiotics of bacterial pathogens is presented. ; Thanks are due to Fernando Rojo and Mary Higgins for proof-reading the manuscript. Work in our laboratory is supported by Grants BIO2011-25255 from the Spanish Ministry of Science and Innovation, PROMPT from CAM, REIPI from the Instituto de Salud Carlos III, and HEALTH-F3- 2011-282004 (EVOTAR) and HEALTH-F3-2010-241476 (PAR) from the European Union. FC is the recipient of a JAE predoctoral fellowship