Law Soffi Kei Kei, Tan Hock Siew
School of Science, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Subang Jaya, Selangor, Malaysia.
School of Science, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Subang Jaya, Selangor, Malaysia; Tropical Medicine and Biology Multidisciplinary Platform, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Subang Jaya, Selangor, Malaysia.
Microbiol Res. 2022 Jul;260:127032. doi: 10.1016/j.micres.2022.127032. Epub 2022 Apr 12.
Acinetobacter baumannii is a nosocomial pathogen responsible for several serious infections, including pneumonia, sepsis, and meningitis. The propensity of this bacterium to rapidly acquire antibiotic resistance leads to the emergence and spread of multidrug-resistant A. baumannii strains. As a result, antibiotics are becoming less effective in treating infections caused by this pathogen. In recent years, increasing efforts have focused on developing therapeutic compounds that could reduce the ability of A. baumannii to establish infection by inhibiting the virulence factors and pathogenesis of this pathogen without interfering with the bacterial viability. These alternative therapeutic options may impose milder selective pressure, reducing the likelihood of anti-virulence resistance development. To develop novel anti-virulence therapies, an in-depth understanding of the bacterial virulence mechanisms is crucial to identifying potential drug targets. This review summarises the latest discoveries about the virulence of A. baumannii, focusing on quorum sensing, biofilm formation, and iron acquisition, along with the corresponding anti-virulence strategies. This article also elaborates on the practical challenges involved in developing anti-virulence drugs. Therapeutic agents that target bacterial virulence factors may play a crucial role in controlling infection in the human host. Combining anti-virulence agents with existing antibiotics could enhance the therapeutic potential of these antibiotics against A. baumannii. Although anti-virulence therapy has been envisioned as an attractive alternative to overcome antimicrobial resistance, additional research on the possibility of developing resistance against anti-virulence drugs is encouraged to evaluate the sustainability of these strategies. Moreover, future studies on the efficacy of anti-virulence therapy against a diverse panel of clinical isolates and in polymicrobial A. baumannii infections are required to provide more valuable information about its clinical application.
鲍曼不动杆菌是一种医院病原体，可导致多种严重感染，包括肺炎、败血症和脑膜炎。这种细菌迅速获得抗生素耐药性的倾向导致了多重耐药鲍曼不动杆菌菌株的出现和传播。因此，抗生素在治疗由这种病原体引起的感染方面正变得越来越无效。近年来，越来越多的努力集中在开发治疗性化合物上，这些化合物可以通过抑制该病原体的毒力因子和发病机制来降低鲍曼不动杆菌建立感染的能力，而不会干扰细菌的生存能力。这些替代治疗选择可能施加较小的选择压力，降低抗毒力耐药性发展的可能性。为了开发新的抗毒力疗法，深入了解细菌毒力机制对于确定潜在的药物靶点至关重要。本综述总结了关于鲍曼不动杆菌毒力的最新发现，重点关注群体感应、生物膜形成和铁获取，以及相应的抗毒力策略。本文还阐述了开发抗毒力药物所涉及的实际挑战。针对细菌毒力因子的治疗剂可能在控制人类宿主感染中发挥关键作用。将抗毒力剂与现有抗生素联合使用可以增强这些抗生素对鲍曼不动杆菌的治疗潜力。尽管抗毒力疗法被设想为克服抗菌药物耐药性的一种有吸引力的替代方法，但鼓励对开发抗毒力药物耐药性的可能性进行更多研究，以评估这些策略的可持续性。此外，未来需要对针对多种临床分离株的抗毒力疗法的疗效以及在多微生物鲍曼不动杆菌感染中的疗效进行研究，以提供有关其临床应用的更有价值的信息。
