Synergistic quinolone sensitization by targeting recA SOS response gene and oxidative stress

Suppression of recA SOS response gene and reactive oxygen species (ROS) overproduction have been shown, separately, to enhance fluoroquinolone activity and lethality. Their putative synergistic impact as a strategy to potentiate the efficacy of bactericidal antimicrobial agents like fluoroquinolones is unknown. We generated Escherichia coli mutants that exhibited suppressed ΔrecA gene in combination with inactivated ROS detoxification system genes (ΔsodA, ΔsodB, ΔkatG, ΔkatE, ΔahpC) or inactivated oxidative stress regulator genes (ΔoxyR, ΔrpoS) to evaluate the interplay of both DNA repair and detoxification systems in drug response. Synergistic sensitization effects, ranging from 7.5- to 30-fold relative to the wild-type, were observed with ciprofloxacin in double knockouts of recA and inactivated detoxification system genes. Compared to recA knockout, inactivation of an additional detoxification system gene reduced MIC values up to 8-fold. In growth curves, no growth was evident in mutants doubly-deficient for recA gene and oxidative detoxification systems at subinhibitory concentrations of ciprofloxacin, in contrast to the recA-deficient strain. There was a marked reduction of viable bacteria in a short period of time when recA gene and other detoxification system genes (katG, sodA or ahpC) were inactivated (using absolute ciprofloxacin concentrations). At 4 hours, a bactericidal effect of ciprofloxacin was observed for ΔkatG/ΔrecA and ΔahpC/ΔrecA double mutants compared to the single ΔrecA mutant (Δ3.4 Log10 CFU/mL). Synergistic quinolone sensitization, by targeting the recA gene and oxidative detoxification stress systems, reinforces the role of both DNA repair systems and ROS in antibiotic-induced bacterial cell death, opening up a new pathway for antimicrobial sensitization.

Joint Action of Two Pesticides and an Oxidase Inhibitor on The Snail Lymnaea Acuminata

Studies were conducted on synergism between an Organophosphate, Nuvan (dichlorvos) mixed with a carbamate, Sevin (carbaryl) in a 1:46 ratio against the snail Lymnaea acuminata. It was found that Sevin enhances the activity of Nuvan and thus the LC values ( LC10, LC50, LC90 ) obtained from this mixture were low as compared to Nuvan or Sevin alone. The acetylcholinesterase (AChE) inhibition was higher in case of Nuvan + Sevin (16.17%) as compared to Nuvan or Sevin (34.7% , 69.1%) alone. When Piperonyl Butoxide (PB), a mixed function oxidase inhibitor was given with Nuvan and Sevin in a 1:46:5 ratio, the LC value decrease still further. It appears that, in the tertiary mixture, while PB reduce the oxidative detoxification of Nuvan and Sevin the carbamate may also be preventing the hydrolysis of Nuvan may tertiary mixture lethal than of its components.

Self-assembly of polyoxovanadate-capped polyoxoniobates and their catalytic decontamination of sulfur mustard simulants

Two novel polyoxovanadate-capped polyoxoniobates with non-classical structural motifs have been successfully assembled, which are active heterogeneous catalysts for the oxidative detoxification of sulfur mustard simulants.