It has been almost 35 years that a major class of antibiotics have been discovered and bacterial are gaining resistance from numerous antibiotics at a much faster rate. Although we continue to ignore this problem, in near future we need to start mitigating the antibiotic resistance. This study may have far reaching effect in the field for this reason. Since bacteria exposed to antibiotic concentration less than MIC can activate SOS response which causes mutagenesis that in turn gives rise to resistant strains, the authors hypothesised that targeting the SOS signal and inhibiting the DSBR process may re-sensitise the bacterial cell to the antibiotic. The study shows how mutations in the SOS protein (recA) and DSBR protein (recB) result in the resistant strain of E. coli to become sensitive to the respective antibiotic. They have also used two small molecule inhibitors for DSBR to check their effect on re-sensitisation.
Some concerns/comments about the study:
- The study could have included screening of drugs from other class of antibiotics. Macrolides, carbapenems and cephalosporins are frequently used classes of antibiotics which many pathogens have attained resistance from, and it would be useful to investigate if DSBR can cause re-sensitisation for these drugs as well.
- The mutants used in study could have been characterised or discussed in more detail for a better understanding of the assays and the results.
- Although the RecA mutants did have a significant effect on the antibiotic sensitivity, result from other mutants of SSGR pathway weren’t that conclusive. But SSGR can also activate SOS response and that may cause mutagenesis even though double strand breaks are not repaired by the cells.
- The target proteins for re-sensitisation have been characterised quite in detail through mutants but the small molecule inhibitor has off-target effects and future research is needed for developing a specific molecule for targeting the DSBR pathway for clinical use. The authors have also raise the concern about the two small molecules used.
The study provides a foundation for further research in the field and provides a good solution to tackle anti-microbial resistance. The data does indicate role of double stand breaks in mutagenesis and resistance although more extensive research is needed for getting a clinical outcome from this.