Department of Biological Sciences, West Liberty University, West Liberty, WV, USA.
Noblis ESI, Chantilly, VA, USA.
Sci Rep. 2021 Dec 14;11(1):24004. doi: 10.1038/s41598-021-03486-3.
Insects are now well recognized as biologically relevant alternative hosts for dozens of mammalian pathogens and they are routinely used in microbial pathogenesis studies. Unfortunately, these models have yet to be incorporated into the drug development pipeline. The purpose of this work was to begin to evaluate the utility of orange spotted (Blaptica dubia) cockroaches in early antibiotic characterization. To determine whether these model hosts could exhibit mortality when infected with bacteria that are pathogenic to humans, we subjected B. dubia roaches to a range of infectious doses of Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii to identify the medial lethal dose. These results showed that lethal disease did not develop following infection of high doses of S. aureus, and A. baumannii. However, cockroaches infected with E. coli and K. pneumoniae succumbed to infection (LD50s of 5.82 × 10 and 2.58 × 10 respectively) suggesting that this model may have limitations based on pathogen specificity. However, because these cockroaches were susceptible to infection from E. coli and K. pneumoniae, we used these bacterial strains for subsequent antibiotic characterization studies. These studies suggested that β-lactam antibiotic persistence and dose was associated with reduction of hemolymph bacterial burden. Moreover, our data indicated that the reduction of bacterial CFU was directly due to the drug activity. Altogether, this work suggests that the orange-spotted cockroach infection model provides an alternative in vivo setting from which antibiotic efficacy can be evaluated.
昆虫现在被公认为数十种哺乳动物病原体具有生物学相关性的替代宿主，它们经常被用于微生物发病机制研究。不幸的是，这些模型尚未被纳入药物开发管道。这项工作的目的是开始评估橙色斑（Blaptica dubia）蟑螂在早期抗生素特性鉴定中的效用。为了确定这些模型宿主在感染对人类具有致病性的细菌时是否会表现出死亡率，我们将 B. dubia 蟑螂暴露于一系列感染剂量的肺炎克雷伯菌、大肠杆菌、金黄色葡萄球菌和鲍曼不动杆菌，以确定半致死剂量。这些结果表明，感染高剂量的金黄色葡萄球菌和鲍曼不动杆菌不会导致致命疾病。然而，感染大肠杆菌和肺炎克雷伯菌的蟑螂因感染而死亡（LD50 分别为 5.82×10 和 2.58×10），这表明该模型可能因病原体特异性而存在局限性。然而，由于这些蟑螂易感染大肠杆菌和肺炎克雷伯菌，我们使用这些细菌株进行了后续的抗生素特性鉴定研究。这些研究表明，β-内酰胺类抗生素的持久性和剂量与减少血淋巴细菌负荷有关。此外，我们的数据表明，细菌 CFU 的减少直接归因于药物活性。总的来说，这项工作表明，橙色斑蟑螂感染模型提供了一种替代的体内环境，可以评估抗生素的疗效。
