Department of Immunobiology, University of Arizonagrid.134563.6 College of Medicine-Tucson, Tucson, Arizona, USA.
Medical Scientist Training M.D.-Ph.D. Program (MSTP), University of Arizonagrid.134563.6 College of Medicine-Tucson, Tucson, Arizona, USA.
Infect Immun. 2022 Apr 21;90(4):e0059721. doi: 10.1128/iai.00597-21. Epub 2022 Mar 21.
Streptococcus pneumoniae is a Gram-positive, encapsulated bacterium that is a significant cause of disease burden in pediatric and elderly populations. The rise in unencapsulated disease-causing strains and antimicrobial resistance in S. pneumoniae has increased the need for developing new antimicrobial strategies. Recent work by our laboratory has identified ,-dimethyldithiocarbamate (DMDC) as a copper-dependent antimicrobial against bacterial, fungal, and parasitic pathogens. As a bactericidal antibiotic against S. pneumoniae, DMDC's ability to work as a copper-dependent antibiotic and its ability to work warranted further investigation. Here, our group studied the mechanisms of action of DMDC under various medium and excess-metal conditions and investigated DMDC's interactions with the innate immune system and . Of note, we found that DMDC plus copper significantly increased the internal copper concentration, hydrogen peroxide stress, nitric oxide stress, and the macrophage killing efficiency and decreased capsule. Furthermore, we found that DMDC treatment increased the quantity of innate immune cells in the lung during infection. Taken together, this study provides mechanistic insights regarding DMDC's activity as an antibiotic at the host-pathogen interface.
肺炎链球菌是一种革兰氏阳性、有荚膜的细菌，是儿科和老年人群疾病负担的重要原因。无荚膜致病菌株的出现以及肺炎链球菌对抗菌药物的耐药性增加，使得人们需要开发新的抗菌策略。我们实验室最近的研究发现，二甲基二硫代氨基甲酸盐（DMDC）是一种铜依赖性抗菌剂，可对抗细菌、真菌和寄生虫病原体。作为一种杀菌抗生素，DMDC 作为铜依赖性抗生素的作用及其能力值得进一步研究。在这里，我们小组研究了 DMDC 在各种培养基和过量金属条件下的作用机制，并研究了 DMDC 与先天免疫系统的相互作用。值得注意的是，我们发现 DMDC 加铜显著增加了细胞内铜浓度、过氧化氢应激、一氧化氮应激以及巨噬细胞杀伤效率，并减少了荚膜。此外，我们发现 DMDC 治疗可增加感染期间肺部中先天免疫细胞的数量。总的来说，这项研究提供了有关 DMDC 作为宿主-病原体界面的抗生素的作用机制的见解。
