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

Qing-Ping Zeng1*, Na Xiao1, Pei Wu1, Xue-Qin Yang2, Li-Xiang Zeng1, Xiao-Xia Guo1, Ping-Zu Zhang1 and Frank Qiu3

Author Affiliations

1 Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou, China

2 Artemisinin Research Centre, Guangzhou University of Chinese Medicine, Guangzhou, China

3 Simplex Biotechnologies, LLC, Clinton, NJ08809, USA

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BMC Research Notes 2011, 4:223  doi:10.1186/1756-0500-4-223

Published: 30 June 2011

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.