Chapters authored
SOS Response and Staphylococcus aureus: Implications for Drug Development
Damage in genetic material is induced through the action of several drugs (directly or indirectly). Specially, antimicrobials from quinolone class (such as ciprofloxacin) induce DNA damage that promotes the formation of the RecA filament 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 effects of new compounds (natural or synthetics) on this pathway. The effects 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 effects of compounds on SOS response from S. aureus.
Part of the book: The Rise of Virulence and Antibiotic Resistance in Staphylococcus aureus
Effects of Alterations in Staphylococcus aureus Cell Membrane and Cell Wall in Antimicrobial Resistance
Staphylococcus aureus is one of the most successful opportunistic pathogen able to cause serious infections due to its ability to produce virulence factors and acquire antimicrobial resistance. Recent reports indicate that the phenotypic changes in the cell wall and cell membrane are essential mechanisms related to the resistance to several antibacterial drugs (such as daptomycin and vancomycin). These alterations involve changes in cell wall composition and chemical modifications of some components (point mutation leading to modification in phosphatidylglycerol molecule, in the production of the aberrations in peptidoglycan structure and decrease in autolytic activity of the components of the cell envelope), leading to changes in electric charge of the cell surface, cell membrane fluidity and cell morphology. In fact, S. aureus develops several multifactorial and strain-specific adaptive mechanisms to survival in host. The study of such mechanisms is very important. The aim of this chapter is to review the phenotypic mechanisms related to drug resistance in S. aureus.
Part of the book: The Rise of Virulence and Antibiotic Resistance in Staphylococcus aureus