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.
Staphylococcus aureus is a notorious pathogenic bacterium causing a wide range of diseases from soft-tissue contamination, to more serious and deep-seated infections. This species is highlighted by its ability to express several kinds of virulence factors and to acquire genes related to drug resistance. Target this number of factors to design any drug is not an easy task. In this review we discuss the importance of computational methods to impulse the development of new drugs against S. aureus. The application of docking methods to screen large library of natural or synthetic compounds and to provide insights into action mechanisms is demonstrated. Particularly, highlighted the studies that validated in silico results with biochemical and microbiological assays. We also comment the computer-aided design of new molecules using some known inhibitors. The confirmation of in silico results with biochemical and microbiological assays allowed the identification of lead molecules that could be used for drug design such as rhodomyrtone, quinuclidine, berberine (and their derivative compounds). The fast development in the computational methods is essential to improve our ability to discovery new drugs, as well as to expand understanding about drug-target interactions.
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