Drug Resistance in Toxoplasma gondii.

Drug Resistance in Toxoplasma gondii.
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DOI:
10.3389/fmicb.2018.02587
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发表时间:
2018
影响因子:
5.2
通讯作者:
Daryani A
Daryani A
中科院分区:
生物学2区
文献类型:
--
作者:
Montazeri M;Mehrzadi S;Sharif M;Sarvi S;Tanzifi A;Aghayan SA;Daryani A

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刚地弓形虫(T. gondii)是一种全球性的原生动物寄生虫,感染了多达三分之一的世界人口。乙胺嘧啶(PYR)和磺胺嘧啶(SDZ)是治疗弓形虫病最广泛使用的药物;然而,也有一些治疗失败的病例被记录下来,这表明存在耐药菌株。本综述旨在对刚地弓形虫的耐药性进行系统而全面的了解,包括耐药机制以及药物在寄生虫中的作用位点。已鉴定出刚地弓形虫酶中的类似氨基酸替换会导致对乙胺嘧啶的耐药性。此外,刚地弓形虫对克林霉素、螺旋霉素和阿奇霉素的耐药性由其核糖体RNA基因编码。然而,刚地弓形虫对磺胺嘧啶的耐药机制尚未得到证实。最近磺胺嘧啶耐药性略有增加。这就是为什么大多数研究使用磺胺嘧啶进行的原因。在2013年至2017年的临床病例中发现了6株对磺胺嘧啶耐药的菌株,在巴西刚地弓形虫分离株中,TgCTBr11、Ck3和Pg1在人类弓形虫病以及供人类食用的家畜中被鉴定出来。总之,近期在临床病例中的实验研究清楚地表明,刚地弓形虫的耐药性正在持续存在。因此,迫切需要建立一种更有效的治疗弓形虫病的方案。本文所综述的对现有药物耐药的刚地弓形虫菌株的出现,不仅关系到治疗失败,还关系到免疫功能低下患者临床病情的加重。为了改善患者的治疗效果,应该更深入地了解刚地弓形虫耐药的确切机制。因此,监测食品中耐药寄生虫的存在似乎是一项审慎的公共卫生计划。
Toxoplasma gondii (T. gondii) is a global protozoan parasite infecting up to one-third of the world population. Pyrimethamine (PYR) and sulfadiazine (SDZ) are the most widely used drugs for treatment of toxoplasmosis; however, several failure cases have been recorded as well; suggesting the existence of drug resistant strains. This review aims to give a systematic and comprehensive understanding of drug resistance in T. gondii including mechanisms of resistance and sites of drug action in parasite. Analogous amino acid substitutions in the Toxoplasma enzyme were identified to confer PYR resistance. Moreover, resistance to clindamycin, spiramycin, and azithromycin is encoded in the rRNA genes of T. gondii. However, T. gondii SDZ resistance mechanism has not been proved yet. Recently there has been a slight increase in SDZ resistance. That is why the majority of studies were carried out using SDZ. Six strains resistant to SDZ were found in clinical cases between 2013 and 2017 which among Brazilian T. gondii isolates, TgCTBr11, Ck3, and Pg1 were identified in human toxoplasmosis, as well as in livestock intended for human consumption. In conclusion, recent experimental studies in clinical cases have clearly shown that drug resistance in Toxoplasma is ongoing. Thus, establishing a more effective therapeutic scheme in the treatment of toxoplasmosis is critically needed. The emergence of T. gondii strains resistant to current drugs, reviewed here, represents a concern not only for treatment failure but also for increased clinical severity in immunocompromised patients. To improve the therapeutic outcome in patients, a greater understanding of the exact mechanisms of drug resistance in T. gondii should be developed. Thus, monitoring the presence of resistant parasites, in food products, would seem a prudent public health program.
弓形虫病发育中的药物:进步,挑战和当前状态。
DOI: 10.2147/dddt.s60973
发表时间: 2017
期刊: Drug design, development and therapy
影响因子: --
作者:
Alday PH;Doggett JS
通讯作者: Doggett JS
DOI: 10.4269/ajtmh.15-0007
发表时间: 2015-09
期刊: The American journal of tropical medicine and hygiene
影响因子: --
作者:
Cui L;Mharakurwa S;Ndiaye D;Rathod PK;Rosenthal PJ
通讯作者: Rosenthal PJ
DOI: 10.1016/j.molbiopara.2013.05.008
发表时间: 2013-07-01
影响因子: 1.5
作者:
Hegewald, Jana;Gross, Uwe;Bohne, Wolfgang
通讯作者: Bohne, Wolfgang
DOI: 10.1017/s0031182011001776
发表时间: 2012-02-01
期刊: PARASITOLOGY
影响因子: 2.4
作者:
Kropf, Christian;Debache, Karim;Hemphill, Andrew
通讯作者: Hemphill, Andrew
DOI: 10.1016/j.exppara.2012.11.019
发表时间: 2013-02-01
影响因子: 2.1
作者:
Doliwa, C.;Escotte-Binet, S.;Villena, I.
通讯作者: Villena, I.