Optimization and Characterization of a Galleria mellonella Larval Infection Model for Virulence Studies and the Evaluation of Therapeutics Against Streptococcus pneumoniae
Optimization and Characterization of a Galleria mellonella Larval Infection Model for Virulence Studies and the Evaluation of Therapeutics Against Streptococcus pneumoniae
复制标题
DOI：
10.3389/fmicb.2019.00311
复制
发表时间：
2019-02-21
影响因子：
5.2
通讯作者：
Cos, Paul
中科院分区：
文献类型：
--
作者：
Cools, Freya;Torfs, Eveline;Cos, Paul
肺炎链球菌是细菌性肺炎的主要原因。感染与高发病率和死亡率有关，并且这种病原体的抗生素耐药性正在上升。因此，需要新的抗菌疗法。为了降低药物发现过程的时间和成本，应考虑替代体内模型。因此，大蜡螟幼虫具有很大的价值。由几种类型的血细胞组成的幼虫免疫与人类先天免疫系统非常相似。此外，这些幼虫不需要特定的住房，价格便宜且易于处理。在这项研究中，建议使用大蜡蚧感染模型来研究早期肺炎球菌感染和治疗。首先，使用不同接种量的链球菌菌株 TIGR4、ATCC (R) 49619、D39 及其荚膜缺陷对应物 R6 证实了该模型研究肺炎球菌毒力因子的适用性。链球菌多糖荚膜被认为是最重要的毒力因子，没有它链球菌就无法维持体内感染。 Kaplan-Meier 存活曲线显示，与菌株 D39 相比，感染链球菌菌株 R6 后幼虫的存活率确实更高。然后，通过测定感染过程中几个时间点的血细胞数量、氧自由基的产生和细菌负荷来表征感染。最后，评估了标准抗生素阿莫西林和莫西沙星对受感染幼虫的治疗。治疗已被证明对感染过程有积极的结果，具体取决于给药剂量。这些数据表明，除了使用幼虫模型研究链球菌特性之外，大蜡螟幼虫还可用于评估针对肺炎链球菌的抗菌疗法。对该模型的深入了解使其更适合在未来的研究中使用。
Streptococcus pneumoniae is the leading cause of bacterial pneumonia. Infection is linked to high morbidity and mortality rates and antibiotic resistance within this pathogen is on the rise. Therefore, there is a need for novel antimicrobial therapies. To lower the time and costs of the drug discovery process, alternative in vivo models should be considered. As such, Galleria mellonella larvae can be of great value. The larval immunity consisting of several types of haemocytes is remarkably similar to the human innate immune system. Furthermore, these larvae don't require specific housing, are cheap and are easy to handle. In this study, the use of a G. mellonella infection model to study early pneumococcal infections and treatment is proposed. Firstly, the fitness of this model to study pneumococcal virulence factors is confirmed using streptococcal strains TIGR4, ATCC (R) 49619, D39 and its capsule-deficient counterpart R6 at different inoculum sizes. The streptococcal polysaccharide capsule is considered the most important virulence factor without which streptococci are unable to sustain an in vivo infection. Kaplan-Meier survival curves showed indeed a higher larval survival after infection with streptococcal strain R6 compared to strain D39. Then, the infection was characterized by determining the number of haemocytes, production of oxygen free radicals and bacterial burden at several time points during the course of infection. Lastly, treatment of infected larvae with the standard antibiotics amoxicillin and moxifloxacin was evaluated. Treatment has proven to have a positive outcome on the course of infection, depending on the administered dosage. These data imply that G. mellonella larvae can be used to evaluate antimicrobial therapies against S. pneumoniae, apart from using the larval model to study streptococcal properties. The in-depth knowledge acquired regarding this model, makes it more suitable for use in future research.