Genetic Mechanisms of Antibiotic Resistance and the Role of Antibiotic Adjuvants

• Published in: Current topics in medicinal chemistry
• Main Authors: Pontes, Daniela Santos, de Araujo, Rodrigo Santos Aquino, Dantas, Natalina, Scotti, Luciana, Scotti, Marcus Tullius, de Moura, Ricardo Olimpio, Mendonca-Junior, Francisco Jaime Bezerra
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2018
• Subjects: efflux pump; antibiotic adjuvants; genetic mechanisms; lactamase; quorum sensing inhibition; antibiotic resistance
• ISSN: 1873-4294
• DOI: 10.2174/1568026618666180206095224

The ever increasing number of multidrug-resistant microorganism pathogens has become a great and global public health threat. Antibiotic mechanisms of action and the opposing mechanisms of resistance are intimately associated, but comprehension of the biochemical and molecular functions of such drugs is not a simple exercise. Both the environment, and genetic settings contribute to alterations in phenotypic resistance (natural bacterial evolution), and make it difficult to control the emergence and impacts of antibiotic resistance. Under such circumstances, comprehension of how bacteria develop and/or acquire antibiotic resistance genes (ARG) has a critical role in developing propositions to fight against these superbugs, and to search for new drugs. In this review, we present and discuss both general information and examples of common genetic and molecular mechanisms related to antibiotic resistance, as well as how the expression and interactions of ARGs is important to drug resistance. At the same time, we focus on recent achievements in the search for antibiotic adjuvants, which help combat antibiotic resistance through deactivation of bacterial mechanisms of action such as ?-lactamases. Recent advances involving the use of anti-resistance drugs such as: efflux pump inhibitors; anti-virulence drugs; drugs against quorum sensing; and against type II/III secretion systems are revealed. Such antibiotic adjuvants (as explored herein) collaborate against the problematic of antibiotic resistance, and may restore or prolong the therapeutic activity of known antibiotics.