Upcroft P, Upcroft J A
Queensland Institute of Medical Research and The Tropical Health Program, Australian Centre for International and Tropical Health and Nutrition, The University of Queensland, The Bancroft Centre, Brisbane, Queensland 4029, Australia.
Clin Microbiol Rev. 2001 Jan;14(1):150-64. doi: 10.1128/CMR.14.1.150-164.2001.
The anaerobic protozoa Giardia duodenalis, Trichomonas vaginalis, and Entamoeba histolytica infect up to a billion people each year. G. duodenalis and E. histolytica are primarily pathogens of the intestinal tract, although E. histolytica can form abscesses and invade other organs, where it can be fatal if left untreated. T. vaginalis infection is a sexually transmitted infection causing vaginitis and acute inflammatory disease of the genital mucosa. T. vaginalis has also been reported in the urinary tract, fallopian tubes, and pelvis and can cause pneumonia, bronchitis, and oral lesions. Respiratory infections can be acquired perinatally. T. vaginalis infections have been associated with preterm delivery, low birth weight, and increased mortality as well as predisposing to human immunodeficiency virus infection, AIDS, and cervical cancer. All three organisms lack mitochondria and are susceptible to the nitroimidazole metronidazole because of similar low-redox-potential anaerobic metabolic pathways. Resistance to metronidazole and other drugs has been observed clinically and in the laboratory. Laboratory studies have identified the enzyme that activates metronidazole, pyruvate:ferredoxin oxidoreductase, to its nitroso form and distinct mechanisms of decreasing drug susceptibility that are induced in each organism. Although the nitroimidazoles have been the drug family of choice for treating the anaerobic protozoa, G. duodenalis is less susceptible to other antiparasitic drugs, such as furazolidone, albendazole, and quinacrine. Resistance has been demonstrated for each agent, and the mechanism of resistance has been investigated. Metronidazole resistance in T. vaginalis is well documented, and the principal mechanisms have been defined. Bypass metabolism, such as alternative oxidoreductases, have been discovered in both organisms. Aerobic versus anaerobic resistance in T. vaginalis is discussed. Mechanisms of metronidazole resistance in E. histolytica have recently been investigated using laboratory-induced resistant isolates. Instead of downregulation of the pyruvate:ferredoxin oxidoreductase and ferredoxin pathway as seen in G. duodenalis and T. vaginalis, E. histolytica induces oxidative stress mechanisms, including superoxide dismutase and peroxiredoxin. The review examines the value of investigating both clinical and laboratory-induced syngeneic drug-resistant isolates and dissection of the complementary data obtained. Comparison of resistance mechanisms in anaerobic bacteria and the parasitic protozoa is discussed as well as the value of studies of the epidemiology of resistance.
厌氧原生动物十二指肠贾第虫、阴道毛滴虫和溶组织内阿米巴每年感染多达10亿人。十二指肠贾第虫和溶组织内阿米巴主要是肠道病原体，尽管溶组织内阿米巴可形成脓肿并侵入其他器官，若不治疗可能致命。阴道毛滴虫感染是一种性传播感染，可导致阴道炎和生殖器黏膜急性炎症性疾病。阴道毛滴虫在尿道、输卵管和盆腔中也有报道，可引起肺炎、支气管炎和口腔病变。呼吸道感染可在围产期获得。阴道毛滴虫感染与早产、低出生体重和死亡率增加有关，还易引发人类免疫缺陷病毒感染、艾滋病和宫颈癌。这三种生物体都缺乏线粒体，由于具有相似的低氧化还原电位厌氧代谢途径，它们对硝基咪唑类药物甲硝唑敏感。临床上和实验室中都观察到了对甲硝唑和其他药物的耐药性。实验室研究已确定激活甲硝唑的酶，即丙酮酸：铁氧化还原蛋白氧化还原酶，将其转化为亚硝基形式，以及每种生物体中诱导药物敏感性降低的不同机制。尽管硝基咪唑类药物一直是治疗厌氧原生动物的首选药物家族，但十二指肠贾第虫对其他抗寄生虫药物，如呋喃唑酮、阿苯达唑和奎纳克林的敏感性较低。已证实每种药物都存在耐药性，并对耐药机制进行了研究。阴道毛滴虫对甲硝唑的耐药性已有充分记录，其主要机制也已明确。在这两种生物体中都发现了旁路代谢，如替代氧化还原酶。讨论了阴道毛滴虫中的需氧与厌氧耐药性。最近利用实验室诱导的耐药分离株对溶组织内阿米巴对甲硝唑的耐药机制进行了研究。与十二指肠贾第虫和阴道毛滴虫中所见的丙酮酸：铁氧化还原蛋白氧化还原酶和铁氧化还原蛋白途径下调不同，溶组织内阿米巴诱导氧化应激机制，包括超氧化物歧化酶和过氧化物酶。本综述探讨了研究临床和实验室诱导的同基因耐药分离株的价值以及对所获得的补充数据的剖析。讨论了厌氧细菌和寄生原生动物耐药机制的比较以及耐药性流行病学研究的价值。
