Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada.
SPARC BioCentre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
FEMS Microbiol Rev. 2016 May;40(3):323-42. doi: 10.1093/femsre/fuv051. Epub 2016 Jan 19.
Antimicrobial resistance is one of the greatest challenges in modern medicine. Infectious diseases that have historically been eliminated with routine antibiotic therapy are now re-emerging as life threatening illnesses. A better understanding of the specific mechanisms that contribute to resistance are required to optimize the treatment of infectious microorganisms and limit the survival of recalcitrant populations. This challenging area of research is made more problematic by the observation that multiple, overlapping, and/or compensatory resistance mechanism are often present within a single bacterial species. High-resolution proteomics has emerged as an effective tool to study antimicrobial resistance as it allows for the quantitative investigation of multiple systems concurrently. Furthermore, the ability to examine extracellular mechanisms of resistance and important post-translational modifications make this research tool well suited for the challenge. This review discusses how proteomics has contributed to the understanding of antimicrobial resistance and focuses on advances afforded by the more recent development of technologies that produce quantitative high-resolution proteomic information. We discuss current strategies for studying resistance, including comparative analysis of resistant and susceptible strains and protein-based responses to antimicrobial challenge. Lastly, we suggest specific experimental approaches aimed at advancing our understanding of protein-based resistance mechanisms and maximizing therapeutic outcomes in the future.
抗菌药物耐药性是现代医学面临的最大挑战之一。过去通过常规抗生素治疗即可消除的感染性疾病，如今再次出现，成为危及生命的疾病。为了优化抗感染微生物的治疗并减少耐药菌的存活，我们需要更好地了解导致耐药性的具体机制。这一具有挑战性的研究领域变得更加复杂，因为观察到在单个细菌物种中通常存在多种、重叠和/或补偿性耐药机制。高分辨率蛋白质组学已成为研究抗菌药物耐药性的有效工具，因为它可以同时定量研究多个系统。此外，该研究工具还能够研究耐药的细胞外机制和重要的翻译后修饰，非常适合解决这一挑战。本文综述了蛋白质组学对抗菌药物耐药性研究的贡献，并重点介绍了近年来高通量、高分辨率蛋白质组学技术发展所带来的进展。我们讨论了目前用于研究耐药性的策略，包括耐药株和敏感株的比较分析以及针对抗菌药物挑战的蛋白质组响应。最后，我们提出了具体的实验方法，旨在深入了解基于蛋白质的耐药机制，并在未来最大限度地提高治疗效果。
