Hibbert Tegan M, Whiteley Marvin, Renshaw Stephen A, Neill Daniel R, Fothergill Joanne L
Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, UK.
School of Biological Sciences, Georgia Institute of Technology, Centre for Microbial Dynamics and Infection, Georgia Institute of Technology, Atlanta, Georgia, USA.
Crit Rev Microbiol. 2024 Nov;50(6):1037-1052. doi: 10.1080/1040841X.2023.2285995. Epub 2023 Nov 24.
is an opportunistic pathogen that is responsible for infections in people living with chronic respiratory conditions, such as cystic fibrosis (CF) and non-CF bronchiectasis (NCFB). Traditionally, in people with chronic respiratory disorders, infection has been managed with a combination of inhaled and intravenous antibiotic therapies. However, due in part to the prolonged use of antibiotics in these people, the emergence of multi-drug resistant strains is a growing concern. The development of anti-virulence therapeutics may provide a new means of treating lung infections whilst also combatting the AMR crisis, as these agents are presumed to exert reduced pressure for the emergence of drug resistance as compared to antibiotics. However, the pipeline for developing anti-virulence therapeutics is poorly defined, and it is currently unclear as to whether and models effectively replicate the complex pulmonary environment sufficiently to enable development and testing of such therapies for future clinical use. Here, we discuss potential targets for anti-virulence therapeutics and the effectiveness of the current models used to study them. Focus is given to the difficulty of replicating the virulence gene expression patterns of in the CF and NCFB lung under laboratory conditions and to the challenges this poses for anti-virulence therapeutic development.
是一种机会致病菌，可导致患有慢性呼吸道疾病的人群感染，如囊性纤维化（CF）和非CF支气管扩张症（NCFB）。传统上，对于患有慢性呼吸道疾病的人群，感染的治疗采用吸入和静脉抗生素联合疗法。然而，部分由于这些人群长期使用抗生素，多重耐药菌株的出现日益受到关注。抗毒力疗法的开发可能提供一种治疗肺部感染的新方法，同时也应对抗菌药物耐药性危机，因为与抗生素相比，这些药物被认为对耐药性出现的压力较小。然而，抗毒力疗法的研发进展尚不明确，目前尚不清楚[具体名称]模型是否能有效充分地复制复杂的肺部环境，以推动此类疗法的研发和测试以供未来临床使用。在此，我们讨论抗毒力疗法的潜在靶点以及用于研究它们的当前模型的有效性。重点关注在实验室条件下复制CF和NCFB肺部中[具体名称]毒力基因表达模式的困难以及这对抗毒力疗法开发带来的挑战。
