GSK Vaccines Institute for Global Health (GVGH) S.r.l., via Fiorentina 1, 53100 Siena, Italy.
Int J Mol Sci. 2021 Apr 14;22(8):4042. doi: 10.3390/ijms22084042.
(Kp) is an opportunistic pathogen and the leading cause of healthcare-associated infections, mostly affecting subjects with compromised immune systems or suffering from concurrent bacterial infections. However, the dramatic increase in hypervirulent strains and the emergence of new multidrug-resistant clones resulted in Kp occurrence among previously healthy people and in increased morbidity and mortality, including neonatal sepsis and death across low- and middle-income countries. As a consequence, carbapenem-resistant and extended spectrum β-lactamase-producing Kp have been prioritized as a critical anti-microbial resistance threat by the World Health Organization and this has renewed the interest of the scientific community in developing a vaccine as well as treatments alternative to the now ineffective antibiotics. Capsule polysaccharide is the most important virulence factor of Kp and plays major roles in the pathogenesis but its high variability (more than 100 different types have been reported) makes the identification of a universal treatment or prevention strategy very challenging. However, less variable virulence factors such as the O-Antigen, outer membrane proteins as fimbriae and siderophores might also be key players in the fight against Kp infections. Here, we review elements of the current status of the epidemiology and the molecular pathogenesis of Kp and explore specific bacterial antigens as potential targets for both prophylactic and therapeutic solutions.
(Kp)是一种机会性病原体,也是导致医疗保健相关感染的主要原因,主要影响免疫系统受损或同时患有细菌感染的人群。然而,高毒力菌株的急剧增加和新的多药耐药克隆的出现导致 Kp 在以前健康的人群中出现,并导致发病率和死亡率增加,包括新生儿败血症和中低收入国家的死亡。因此,耐碳青霉烯类和产超广谱β-内酰胺酶的 Kp 已被世界卫生组织列为关键的抗微生物耐药性威胁,并重新引起科学界对开发疫苗以及替代目前无效抗生素的治疗方法的兴趣。荚膜多糖是 Kp 最重要的毒力因子,在发病机制中起主要作用,但它的高度可变性(已报道超过 100 种不同类型)使得确定通用的治疗或预防策略极具挑战性。然而,像 O-抗原、菌毛和铁载体这样的较少变异性的毒力因子也可能是对抗 Kp 感染的关键因素。在这里,我们回顾了 Kp 的流行病学和分子发病机制的现状,并探讨了特定的细菌抗原作为预防和治疗解决方案的潜在靶点。