PURPOSE: The role of antibiotics below their MIC in the development of bacterial drug resistance is becoming increasingly important. We investigated the effect of sub-MICs of bactericidal antibiotics on the susceptibility pattern of Staphylococcus aureus and evaluated the role of free radicals. METHODOLOGY: A total of 12 S. aureus strains were recovered from pus samples and their antibiograms determined. The test isolates were treated with sub-MIC levels of tetracycline, gentamicin, ciprofloxacin and cefotaxime. Alterations in their respective breakpoints were observed along with measurements of free radical generation by nitro blue tetrazolium test.Results/Key findings. Gentamicin, ciprofloxacin and cefotaxime exposure significantly altered the breakpoints of exposed isolates against several tested antibiotics and higher levels of free radicals were generated after antibiotic exposure. CONCLUSIONS: Our study demonstrates that sub-MIC levels of antimicrobials can lead to resistance and cross-resistance across several classes of antibiotics in wild strains of S. aureus, possibly by free radical production. The molecular mechanisms behind the acquisition of drug resistance at low antibiotic concentrations and the specific target genes of reactive oxygen speciesneed to be explored further.
PURPOSE: The role of antibiotics below their MIC in the development of bacterial drug resistance is becoming increasingly important. We investigated the effect of sub-MICs of bactericidal antibiotics on the susceptibility pattern of Staphylococcus aureus and evaluated the role of free radicals. METHODOLOGY: A total of 12 S. aureus strains were recovered from pus samples and their antibiograms determined. The test isolates were treated with sub-MIC levels of tetracycline, gentamicin, ciprofloxacin and cefotaxime. Alterations in their respective breakpoints were observed along with measurements of free radical generation by nitro blue tetrazolium test.Results/Key findings. Gentamicin, ciprofloxacin and cefotaxime exposure significantly altered the breakpoints of exposed isolates against several tested antibiotics and higher levels of free radicals were generated after antibiotic exposure. CONCLUSIONS: Our study demonstrates that sub-MIC levels of antimicrobials can lead to resistance and cross-resistance across several classes of antibiotics in wild strains of S. aureus, possibly by free radical production. The molecular mechanisms behind the acquisition of drug resistance at low antibiotic concentrations and the specific target genes of reactive oxygen speciesneed to be explored further.
Authors: Oren Gordon; Donald E Lee; Bessie Liu; Brooke Langevin; Alvaro A Ordonez; Dustin A Dikeman; Babar Shafiq; John M Thompson; Paul D Sponseller; Kelly Flavahan; Martin A Lodge; Steven P Rowe; Robert F Dannals; Camilo A Ruiz-Bedoya; Timothy D Read; Charles A Peloquin; Nathan K Archer; Lloyd S Miller; Kimberly M Davis; Jogarao V S Gobburu; Sanjay K Jain Journal: Sci Transl Med Date: 2021-12-01 Impact factor: 17.956
Authors: Madhan R Tirumalai; Fathi Karouia; Quyen Tran; Victor G Stepanov; Rebekah J Bruce; C Mark Ott; Duane L Pierson; George E Fox Journal: mBio Date: 2019-01-15 Impact factor: 7.867