Combined inactivation of the SOS response with TCA fumarases and the adaptive response enhances antibiotic susceptibility against Escherichia coli

Overall, no significant differences or only moderate increases in susceptibility were observed in the single mutants, with Δ<i>fumC</i> and Δ<i>aidB</i> mutants showing the highest susceptibility. To enhance this effect, these genes were then inactivated in combination with the SOS response by constructing Δ<i>fumC</i>/Δ<i>recA</i> and Δ<i>aidB</i>/Δ<i>recA</i> mutants. These combinations exhibited significant differences in susceptibility to various antimicrobials, particularly cephalosporins and quinolones, and especially in the Δ<i>fumC</i>/Δ<i>recA</i> strain. To further assess these results, we constructed an <i>E. coli</i> ST131 Δ<i>fumC</i>/Δ<i>recA</i> mutant, in which a similar trend was observed. Together, these findings suggest that co-targeting the SOS response together with fumarases or the adaptive response could enhance the effectiveness of antibiotics against <i>E. coli</i>, potentially leading to new therapeutic strategies.