Artesunate has its enhancement on antibacterial activity of β-lactams via increasing the antibiotic accumulation within methicillin-resistant Staphylococcus aureus (MRSA)

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has now emerged as a predominant and serious pathogen because of its resistance to a large group of antibiotics, leading to high morbidity and mortality. Therefore, to develop new agents against resistance is urgently required. Previously, artesunate (AS) was found to enhance the antibacterial effect of β-lactams against MRSA. In this study, AS was first found to increase the accumulation of antibiotics (daunorubicin and oxacillin) within MRSA by laser confocal microscopy and liquid chromatography-tandem MS method, suggesting the increased antibiotics accumulation might be related to the enhancement of AS on antibiotics. Furthermore, AS was found not to destroy the cell structure of MRSA by transmission electron microscope. AS was found to inhibit gene expressions of important efflux pumps such as NorA, NorB and NorC, but not MepA, SepA and MdeA. In conclusion, our results showed that AS was capable of enhancing the antibacterial activity of β-lactams via increasing antibiotic accumulations within MRSA through inhibiting gene expressions of efflux pumps such as NorA, NorB and NorC, but did not destroy the cell structure of MRSA. AS could be further investigated as a candidate drug for treatment of MRSA infection.

Artesunate inhibits Staphylococcus aureus biofilm formation by reducing alpha-toxin synthesis

“…Artesunate (AS), a water-soluble hemisuccinate derivative of dihydroartemisinin, is widely used to treat malaria. Previously, in our laboratory, AS was revealed to increase the susceptibility of various β-lactam antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) by inhibiting the gene expression of efflux pumps (Jiang et al 2013). During the study, we also found that AS had an inhibitory effect on the biofilm formation of S. aureus; therefore, in this study, we further investigated the effects and possible mechanisms of AS on the inhibition of S. aureus biofilm formation.…”

Efficacy of ampicillin against methicillin-resistant Staphylococcus aureus restored through synergy with branched poly(ethylenimine)

“…1, 7, 8 Therapeutic approaches to overcome resistance factors include efflux-pump inhibitors that increase the intracellular concentration of antibiotics. 9 Bacteria can also use β-lactamase enzymes that degrade the antibiotics 10 and thus treatment requires β-lactamase inhibitors. 11 …”

Strategies for Circumventing Bacterial Resistance Mechanisms

“…As we transition from populations at particular risk of bacterial infection -such as the transplant recipient (Bodro et al 2013), the immunocompromised (Bow 2013), and the critically ill (Cohen 2013) -to the entire populations at risk, such may result from the entry of pathogenic bacteria into the food supply (Le Hello et al 2013), neither new structures nor new technologies may alone suffice to provide the antibacterial future. We will need to aggressively evaluate empirical opportunities, such as pursuing repurposed compounds that act to sensitize (Thorsing et al 2013) or to attenuate quorum sensing (Imperi et al 2013b;O'Loughlin et al 2013), virulence (Imperi et al 2013a;Long et al 2013), and efflux (Jiang et al 2013). Reassessing old discovery strategies as well as implementing new strategies will be required (Shapiro 2013;Tegos and Hamblin 2013).…”