Guanine Nucleotide Oxidation and Cell Death by Bactericidal Antibiotics

Autor: Harikrishna Pillai, Harikumar S Kartha, Anuraj K S Anuraj K S
Rok vydání: 2012
Předmět:
Zdroj: Global Journal For Research Analysis. 3:273-274
ISSN: 2277-8160
DOI: 10.15373/22778160/july2014/98
Popis: Emergence of antibiotic resistance by pathogenic bacteria is a very serious problem nowadays. So for the derivation of new class of antibiotics and clinically useful adjuvants for current antimicrobial therapies, a detailed understanding of the mechanisms underlying the antibiotic killing is important. Its shown that the three major classes of bactericidal antibiotics (β-lactams, quinolones and aminoglycosides), regardless of drug target interaction, stimulate the production of highly deleterious hydroxyl radical in gram negative and gram positive bacteria. These hydroxyl radicals ultimately cause cell death by specific oxidation of guanine nucleotide pool and its subsequent use in nucleic acid transactions by a tranlesion DNA polymerase called Din B polymerase that can use 8-oxodeoxyguanosine triphosphate (8-oxo-dGTP) as the incoming nucleotide pairing it with either deoxycytidine or deoxyadenosine (dC or dA), with a preference to dA. This will lead to accumulation of lethal mutations or formation of lethal double stranded breaks (DSB) resulting in cell death.
Databáze: OpenAIRE