Abstract
BackgroundA current challenge of coping with bacterial infection is that bacterial pathogens are becoming less susceptible to or more tolerant of commonly used antibiotics. It is urgent to work out a practical solution to combat the multidrug resistant bacterial pathogens.FindingsOxidative stress-acclimatized bacteria thrive in rifampicin by generating antibiotic-detoxifying nitric oxide (NO), which can be repressed by artesunate or an inhibitor of nitric oxide synthase (NOS). Suppressed bacterial proliferation correlates with mitigated NO production upon the combined treatment of bacteria by artesunate with antibiotics. Detection of the heme-artesunate conjugate and accordingly declined activities of heme-harbouring bacterial NOS and catalase indicates that artesunate renders bacteria susceptible to antibiotics by alkylating the prosthetic heme group of hemo-enzymes.ConclusionsBy compromising NO-mediated protection from antibiotics and triggering harmful hydrogen peroxide burst, artesunate may serve as a promising antibiotic synergist for killing the multidrug resistant pathogenic bacteria.
Highlights
A current challenge of coping with bacterial infection is that bacterial pathogens are becoming less susceptible to or more tolerant of commonly used antibiotics
By compromising nitric oxide (NO)-mediated protection from antibiotics and triggering harmful hydrogen peroxide burst, artesunate may serve as a promising antibiotic synergist for killing the multidrug resistant pathogenic bacteria
A gradual increase of nitrate/nitrite, the oxidation product of NO, was detected in the bacterial culture standing without agitation either at room temperature or in a 4°C refrigerator no significant difference was observed between the hypoxia + cold group and the hypoxia group (Figure 1)
Summary
A current challenge of coping with bacterial infection is that bacterial pathogens are becoming less susceptible to or more tolerant of commonly used antibiotics. Incubation of E. coli with ART/ART+Cef the heme-artemisinin adduct in malaria-infected mice [6], and the interaction between heme and artesunate has been recognised by monitoring the dynamic shift of one peak specific to heme and another peak unique to the heme-artesunate conjugate in tumour cells [7], we assumed that artesunate would bind to the heme group of bacterial NOS and prohibit the inter-conversion of Fe3+ with Fe2+ within the hemoprotein. We further measured catalase activity after incubating bacteria with rifampicin or rifampicin + artesunate.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
