SOS Response and Staphylococcus aureus: Implications for Drug Development

Abstract

Damage in genetic material is induced through the action of several drugs (directly or indirectly). Specially, antimicrobials from quinolone class (such as ciproloxacin) induce DNA damage that promotes the formation of the RecA ilament leading to auto-cleavage of LexA and allows the expression of SOS genes, including the error-prone polymerase (like umuC). The SOS pathway plays a critical role in the acquisition of mutations that lead to the emergence of antibiotic-resistant bacteria and the spread of virulence factors. This chapter provides a comprehensive review about the SOS response of Staphylococcus aureus and the modulatory efects of new compounds (natural or synthetics) on this pathway. The efects of some SOS inhibitors are highlighted such as baicalein and aminocoumarins. Compounds able to prevent SOS response are extremely important to develop new combinatory approaches to inhibit S. aureus mutagenesis. The study of new SOS inductors could reveal new insights into the pathways used by S. aureus to acquire drug resistance; examples of these compounds are the lysine-peptoid hybrid LP5, cyclic peptide inhibitors, etc. These studies can impact the development of new drugs. In conclusion, we hope to provide essential information about the efects of compounds on SOS response from S. aureus.

Antibacterial effects of nanopillar surfaces are mediated by cell impedance, penetration and induction of oxidative stress

“…Expression of such proteins is induced by H 2 O 2 stress 31 . SOS response proteins UvrA and UvrC, and bleomycin resistance protein had also increased significantly in the presence of NW-850-5, which mediate repair of DNA damage 32,33 , along with histone-like DNA-binding protein HU, which is involved in DNA stabilisation under extreme environmental conditions 34 . In addition to oxidative stress, another key theme of S. aureus DEPs was protein expression.…”

“…10a). Given that ROS mediate damage of DNA, lipids and proteins 32,39 , the increased quantity of H 2 O 2 could be expected to induce changes in bacterial envelope morphology. Following 24-h incubation, the density and coverage of S. aureus and E. coli were notably higher on control compared to NW-850-5 discs ( Fig.…”

Antibiotic Tolerance of Staphylococcus aureus Biofilm in Periprosthetic Joint Infections and Antibiofilm Strategies

“…As biofilm emerges as a stress response to hostile environment, different SOS systems are triggered in the presence of stressful conditions, such as antibiotic treatments, starvation, or oxidative stress, to repair damaged DNA caused by these threats [ 79 ]. Starvation and the associated SOS response can mediate biofilm-specific tolerance to antibiotic such as ofloxacine, and it was also shown that subinhibitory concentrations of quinolones can induce an SOS response and elevate the mutation rate [ 80 , 81 ].…”

“…Generated by the host, reactive oxygen species are also linked with antibiotic tolerance during systemic S. aureus infections [ 82 ]. The SOS response also affects the expression of virulence factors, mutagenesis, and the frequency of SCVs [ 79 , 83 ]. This phenotype switch in S. aureus is described as a consequence of drug treatments, reactive oxygen species, low pH, and starvation, and is also linked to the internalization ability [ 12 , 36 ].…”