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Artesunate potentiates antibiotics by inactivating heme-harbouring bacterial nitric oxide synthase and catalase

Author(s): Zeng Qing-Ping | Xiao Na | Wu Pei | Yang Xue-Qin | Zeng Li-Xiang | Guo Xiao-Xia | Zhang Ping-Zu | Qiu Frank

Journal: BMC Research Notes
ISSN 1756-0500

Volume: 4;
Issue: 1;
Start page: 223;
Date: 2011;
Original page

Abstract Background A 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. Findings Oxidative 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. Conclusions By 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.
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