Bacterial resistance mechanism: what proteomics can elucidate

Abstract

Antibiotics are important therapeutic agents commonly used for the control of bacterial infectious diseases; however, resistance to antibiotics has become a global public health problem. Therefore, effective therapy in the treatment of resistant bacteria is necessary and, to achieve this, a detailed understanding of mechanisms that underlie drug resistance must be sought. To fill the multiple gaps that remain in understanding bacterial resistance, proteomic tools have been used to study bacterial physiology in response to antibiotic stress. In general, the global analysis of changes in the protein composition of bacterial cells in response to treatment with antibiotic agents has made it possible to construct a database of proteins involved in the process of resistance to drugs with similar mechanisms of action. In the past few years, progress in using proteomic tools has provided the most realistic picture of the infective process, since these tools detect the end products of gene biosynthetic pathways, which may eventually determine a biological phenotype. In most bacterial species, alterations occur in energy and nitrogen metabolism regulation; glucan biosynthesis is up-regulated; amino acid, protein, and nucleotide synthesis is affected; and various proteins show a stress response after exposing these microorganisms to antibiotics. These issues have been useful in identifying targets for the development of novel antibiotics and also in understanding, at the molecular level, how bacteria resist antibiotics.

The Resistant-Population Cutoff (RCOFF): a New Concept for Improved Characterization of Antimicrobial Susceptibility Patterns of Non-Wild-Type Bacterial Populations

“…To ensure the correct assignment of isolates in the overlapping zone, either additional investigations on the presence of potential resistance mechanisms or a relatively wide intermediate zone is required (12). Increasing knowledge of the different molecular resistance mechanisms present in clinical isolates will allow establishment of resistotype-associated RCOFF values, facilitating the correlation of the in vitro AST data with the clinical outcome, a prerequisite for the setting and validation of CBPs (31)(32)(33)(34)(35).…”

Implicancias Estructurales y Fisiológicas de la Célula Bacteriana en los Mecanismos de Resistencia Antibiótica

“…Ejemplo de ello son las mutaciones DNA topoisomerasas gyrA, gyrB y parC, responsables de la resistencia a fluoroquinolonas en Coxiella burnetii (Lima et al, 2013).…”

Global analysis of bacterial membrane proteins and their modifications

“…In a shotgun-based proteomic study an altered outer membrane protein profile was found in clarithromycin resistant Helicobacter pylori (Smiley et al, 2013). Further proteomic based studies describing the importance of OMPs is extensively described elsewhere (Lima et al, 2013).…”