Department of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.
Division of Oral and Craniofacial Health Sciences, University of North Carolina at Chapel Hill Adams School of Dentistry, Chapel Hill, North Carolina, USA.
Infect Immun. 2024 Sep 10;92(9):e0050923. doi: 10.1128/iai.00509-23. Epub 2024 Mar 25.
Diabetes mellitus, characterized by impaired insulin signaling, is associated with increased incidence and severity of infections. Various diabetes-related complications contribute to exacerbated bacterial infections, including hyperglycemia, innate immune cell dysfunction, and infection with antibiotic-resistant bacterial strains. One defining symptom of diabetes is hyperglycemia, resulting in elevated blood and tissue glucose concentrations. Glucose is the preferred carbon source of several bacterial pathogens, and hyperglycemia escalates bacterial growth and virulence. Hyperglycemia promotes specific mechanisms of bacterial virulence known to contribute to infection chronicity, including tissue adherence and biofilm formation. Foot infections are a significant source of morbidity in individuals with diabetes and consist of biofilm-associated polymicrobial communities. Bacteria perform complex interspecies behaviors conducive to their growth and virulence within biofilms, including metabolic cross-feeding and altered phenotypes more tolerant to antibiotic therapeutics. Moreover, the metabolic dysfunction caused by diabetes compromises immune cell function, resulting in immune suppression. Impaired insulin signaling induces aberrations in phagocytic cells, which are crucial mediators for controlling and resolving bacterial infections. These aberrancies encompass altered cytokine profiles, the migratory and chemotactic mechanisms of neutrophils, and the metabolic reprogramming required for the oxidative burst and subsequent generation of bactericidal free radicals. Furthermore, the immune suppression caused by diabetes and the polymicrobial nature of the diabetic infection microenvironment may promote the emergence of novel strains of multidrug-resistant bacterial pathogens. This review focuses on the "triple threat" linked to worsened bacterial infections in individuals with diabetes: (i) altered nutritional availability in diabetic tissues, (ii) diabetes-associated immune suppression, and (iii) antibiotic treatment failure.
糖尿病的特征是胰岛素信号受损，与感染的发生率和严重程度增加有关。各种与糖尿病相关的并发症导致细菌感染加重，包括高血糖、先天免疫细胞功能障碍和对抗生素耐药的细菌菌株感染。糖尿病的一个明确症状是高血糖，导致血液和组织中的葡萄糖浓度升高。葡萄糖是几种细菌病原体的首选碳源，高血糖会加速细菌的生长和毒力。高血糖促进了细菌毒力的特定机制，已知这些机制有助于感染的慢性化，包括组织黏附和生物膜形成。足部感染是糖尿病患者发病率的一个重要来源，由生物膜相关的多微生物群落组成。细菌在生物膜内进行有利于其生长和毒力的复杂种间行为，包括代谢交叉喂养和改变对抗生素治疗更耐受的表型。此外，糖尿病引起的代谢功能障碍会损害免疫细胞的功能，导致免疫抑制。胰岛素信号受损会导致吞噬细胞发生异常，吞噬细胞是控制和解决细菌感染的关键介质。这些异常包括细胞因子谱改变、中性粒细胞的迁移和趋化机制以及氧化爆发和随后产生杀菌自由基所需的代谢重编程。此外，糖尿病引起的免疫抑制和糖尿病感染微环境的多微生物性质可能会促进新型多药耐药细菌病原体的出现。本综述重点介绍了与糖尿病患者细菌感染恶化相关的“三重威胁”：（i）糖尿病组织中营养物质可用性的改变，（ii）与糖尿病相关的免疫抑制，以及（iii）抗生素治疗失败。
