ABSTRACT

Neisseria gonorrhoeae (gonococcus) causes the human sexually transmitted disease gonorrhea. Studying gonococcal pathogenesis and developing new vaccines and therapies to combat the increasing prevalence of multi-antibiotic resistant bacteria has made use of many ex vivo models based on human cells and tissues, and in vivo vertebrate models, for example, rodent, pig and human. The focus of the current study was to examine the utility of the invertebrate greater wax moth Galleria mellonella as an in vivo model of gonococcal infection. We observed that a threshold of ~10⁶ – 10⁷ gonococci/larva was required to kill >50% of larvae (P < 0.05), and increased toxicity correlated with reduced health index scores and pronounced histopathological changes such as increases in the total lesion grade, melanized nodules, hemocyte reaction, and multifocal adipose body degeneration. Larval death was independent of the expression of pilus or Opa protein or LOS sialylation within a single gonococcal species studied, but the model could demonstrate relative toxicity of different isolates. N. meningitidis, N. lacatamica and gonococci all killed larvae equally, but were significantly less toxic (P > 0.05) than Pseudomonas aeruginosa. Larvae primed with nontoxic doses of gonococci were more susceptible to subsequent challenge with homologous and heterologous bacteria, and larval survival was significantly reduced (P < 0.05) in infected larvae after depletion of their hemocytes with clodronate-liposomes. The model was used to test the anti-gonococcal properties of antibiotics and novel antimicrobials. Ceftriaxone (P < 0.05) protected larvae from infection with different gonococcal isolates, but not azithromycin or monocaprin or ligand-coated silver nanoclusters (P > 0.05).

 抽象的

淋病奈瑟菌（淋球菌）导致人类性传播疾病淋病。研究淋球菌发病机制并开发新的疫苗和疗法来对抗日益流行的多重抗生素耐药细菌，使用了许多基于人体细胞和组织的离体模型，以及啮齿动物、猪和人类等体内脊椎动物模型。当前研究的重点是检验无脊椎动物大蜡蛾作为淋球菌感染体内模型的效用。我们观察到，需要~10 ⁶ – 10 ⁷淋球菌/幼虫的阈值才能杀死> 50%的幼虫（P < 0.05），并且毒性增加与健康指数评分降低和显着的组织病理学变化（例如总病变增加）相关级、黑化结节、血细胞反应和多灶性脂肪体变性。幼虫死亡与所研究的单一淋球菌物种中菌毛或 Opa 蛋白的表达或 LOS 唾液酸化无关，但该模型可以证明不同分离株的相对毒性。脑膜炎奈瑟氏球菌、内乳奈瑟氏球菌和淋球菌对幼虫的杀灭作用均相同，但毒性显着低于铜绿假单胞菌（P > 0.05）。用无毒剂量的淋球菌引发的幼虫更容易受到同源和异源细菌的后续攻击，并且在用氯膦酸盐脂质体耗尽受感染幼虫的血细胞后，幼虫存活率显着降低（P < 0.05）。该模型用于测试抗生素和新型抗菌药物的抗淋球菌特性。头孢曲松 (P < 0.05) 可以保护幼虫免受不同淋球菌分离株的感染，但不能保护阿奇霉素、单癸酸或配体包被的银纳米簇（P > 0.05）。