Jackson Catherine A, McKean Elise L, Hawdon John M
Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC 20052, USA.
Department of Biological Sciences, The George Washington University, Washington, DC 20052, USA.
Trop Med Infect Dis. 2025 Jun 27;10(7):181. doi: 10.3390/tropicalmed10070181.
Multi-anthelmintic resistance in hookworms poses a significant challenge to both human and veterinary health, underscoring the need for novel treatment strategies. In this study, we evaluated the in vitro efficacy of three anthelmintics-pyrantel, ivermectin, and emodepside-against L3 larvae of drug-susceptible (WMD) and triple-anthelmintic-resistant (BCR) isolates of . While pyrantel was largely ineffective and ivermectin induced high mortality in both isolates, emodepside displayed a surprising trend: the drug-resistant BCR isolate was more susceptible than the drug-susceptible WMD isolate. To explore the underlying mechanism, we performed survival assays in the presence of penitrem A, a BK channel (SLO-1) inhibitor. The addition of penitrem A reversed the enhanced emodepside sensitivity in BCR, implicating elevated basal expression of SLO-1 channels as a potential factor. These findings suggest that emodepside, via its action on SLO-1, may offer a promising therapeutic avenue to combat multidrug-resistant hookworm infections.
钩虫的多重抗蠕虫药耐药性对人类和兽医健康都构成了重大挑战，这凸显了新型治疗策略的必要性。在本研究中，我们评估了三种抗蠕虫药——噻嘧啶、伊维菌素和埃莫昔肽——对药物敏感（WMD）和三重抗蠕虫药耐药（BCR）分离株的L3幼虫的体外疗效。虽然噻嘧啶在很大程度上无效，且伊维菌素在两种分离株中均诱导了高死亡率，但埃莫昔肽呈现出一个惊人的趋势：耐药的BCR分离株比药物敏感的WMD分离株更易受影响。为了探究潜在机制，我们在存在青霉震颤素A（一种BK通道（SLO-1）抑制剂）的情况下进行了存活试验。添加青霉震颤素A逆转了BCR中增强的埃莫昔肽敏感性，这表明SLO-1通道的基础表达升高是一个潜在因素。这些发现表明，埃莫昔肽通过其对SLO-1的作用，可能为对抗多重耐药钩虫感染提供一条有前景的治疗途径。
