Zeng Qing-Ping, Xiao Na, Wu Pei, Yang Xue-Qin, Zeng Li-Xiang, Guo Xiao-Xia, Zhang Ping-Zu, Qiu Frank
Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou, China.
BMC Res Notes. 2011 Jun 30;4:223. doi: 10.1186/1756-0500-4-223.
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.
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.
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.
应对细菌感染当前面临的一个挑战是，细菌病原体对常用抗生素的敏感性越来越低或耐受性越来越强。迫切需要制定切实可行的解决方案来对抗多重耐药细菌病原体。
适应氧化应激的细菌通过产生可解毒抗生素的一氧化氮（NO）在利福平中茁壮生长，而青蒿琥酯或一氧化氮合酶（NOS）抑制剂可抑制这种情况。青蒿琥酯与抗生素联合处理细菌后，细菌增殖受到抑制，这与NO生成减少相关。检测到血红素 - 青蒿琥酯共轭物以及相应的含血红素细菌NOS和过氧化氢酶活性下降，表明青蒿琥酯通过烷基化血红素酶的辅基血红素基团使细菌对抗生素敏感。
通过损害NO介导的对抗生素的保护作用并引发有害的过氧化氢爆发，青蒿琥酯可能成为一种有前景的抗生素增效剂，用于杀死多重耐药病原菌。
