The SOS response aids bacterial propagation by inhibiting cell division during repair of DNA damage. We report that inactivation of the ftsI gene product, penicillin binding protein 3, by either β-lactam antibiotics or genetic mutation induces SOS in Escherichia coli through the DpiBA two-component signal transduction system. This event, which requires the SOS-promoting recA and lexA genes as well as dpiA , transiently halts bacterial cell division, enabling survival to otherwise lethal antibiotic exposure. Our findings reveal defective cell wall synthesis as an unexpected initiator of the bacterial SOS response, indicate that β-lactam antibiotics are extracellular stimuli of this response, and demonstrate a novel mechanism for mitigation of antimicrobial lethality.
Staphylococcus aureus is capable of becoming resistant to all classes of antibiotics clinically available and resistance can develop through de novo mutations in chromosomal genes or through acquisition of horizontally transferred resistance determinants. This review covers the most important antibiotics available for treatment of S. aureus infections and a special emphasis is dedicated to the current knowledge of the wide variety of resistance mechanisms that S. aureus employ to withstand antibiotics. Since resistance development has been inevitable for all currently available antibiotics, new therapies are continuously under development. Besides development of new small molecules affecting cell viability, alternative approaches including anti-virulence and bacteriophage therapeutics are being investigated and may become important tools to combat staphylococcal infections in the future.
1 June 2019 in International Journal of Antimicrobial Agents
Resveratrol is a naturally occurring polyphenolic antioxidant that has received massive attention for its potential health benefits, including anticarcinogenesis, anti-aging and antimicrobial properties. The compound is well tolerated by humans and in recent years has been widely used as a nutraceutical. Its common use makes it interesting to investigate with respect to antimicrobial properties both as a single agent and in combination with conventional antibiotics. Resveratrol displays antimicrobial activity against a surprisingly wide range of bacterial, viral and fungal species. At subinhibitory concentrations, resveratrol can alter bacterial expression of virulence traits leading to reduced toxin production, inhibition of biofilm formation, reduced motility and interference with quorum sensing. In combination with conventional antibiotics, resveratrol enhances the activity of aminoglycosides against Staphylococcus aureus, whereas it antagonises the lethal activity of fluoroquinolones against S. aureus and Escherichia coli. Whilst the antimicrobial properties of the compound have been extensively studied in vitro, little is known about its efficacy in vivo. Nonetheless, following topical application resveratrol has alleviated acne lesions caused by the bacterium Propionibacterium acnes. There are currently no in vivo studies addressing its effect in combination with antibiotics, but recent research suggests that there may be a potential for enhancing the antimicrobial efficacy of certain existing antibiotic classes in combination with resveratrol. Given the difficulties associated with introducing new antimicrobial agents to the market, nutraceuticals such as resveratrol may prove to be interesting candidates when searching for solutions for the growing problem of antimicrobial resistance.