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Expert Opin Drug Discov


Title:Non-genetic mechanisms communicating antibiotic resistance: rethinking strategies for antimicrobial drug design
Author(s):El-Halfawy OM; Valvano MA;
Address:"University of Western Ontario, Center for Human Immunology, Departments of Microbiology and Immunology, and Medicine, London, Ontario, Canada"
Journal Title:Expert Opin Drug Discov
Year:2012
Volume:20120804
Issue:10
Page Number:923 - 933
DOI: 10.1517/17460441.2012.712512
ISSN/ISBN:1746-045X (Electronic) 1746-0441 (Linking)
Abstract:"INTRODUCTION: Infections by multidrug-resistant bacteria are of great concern worldwide. In many cases, resistance is not due to the presence of specific antibiotic-modifying enzymes, but rather associated with a general impermeability of the bacterial cell envelope. The molecular bases of this intrinsic resistance are not completely understood. Moreover, horizontal gene transfers cannot solely explain the spread of intrinsic resistance among bacterial strains. AREAS COVERED: This review focuses on the increased intrinsic antibiotic resistance mediated by small molecules. These small molecules can either be secreted from bacterial cells of the same or different species (e.g., indole, polyamines, ammonia, and the Pseudomonas quinolone signal) or be present in the bacterial cell milieu, whether in the environment, such as indole acetic acid and other plant hormones, or in human tissues and body fluids, such as polyamines. These molecules are metabolic byproducts that act as infochemicals and modulate bacterial responses toward antibiotics leading to increasing or decreasing resistance levels. EXPERT OPINION: The non-genetic mechanisms of antibiotic response modulation and communication discussed in this review should reorient our thinking of the mechanisms of intrinsic resistance to antibiotics and its spread across bacterial cell populations. The identification of chemical signals mediating increased intrinsic antibiotic resistance will expose novel critical targets for the development of new antimicrobial strategies"
Keywords:"Anti-Bacterial Agents Bacteria/metabolism Drug Design Drug Resistance, Bacterial/*physiology Humans;"
Notes:"MedlineEl-Halfawy, Omar M Valvano, Miguel A eng Canadian Institutes of Health Research/Canada Research Support, Non-U.S. Gov't Review England 2012/08/07 Expert Opin Drug Discov. 2012 Oct; 7(10):923-33. doi: 10.1517/17460441.2012.712512. Epub 2012 Aug 4"

 
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