Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.
Cell Host Microbe. 2024 Jun 12;32(6):852-862. doi: 10.1016/j.chom.2024.04.019.
Antibiotic resistance, typically associated with genetic changes within a bacterial population, is a frequent contributor to antibiotic treatment failures. Antibiotic persistence and tolerance, which we collectively term recalcitrance, represent transient phenotypic changes in the bacterial population that prolong survival in the presence of typically lethal concentrations of antibiotics. Antibiotic recalcitrance is challenging to detect and investigate-traditionally studied under in vitro conditions, our understanding during infection and its contribution to antibiotic failure is limited. Recently, significant progress has been made in the study of antibiotic-recalcitrant populations in pathogenic species, including Mycobacterium tuberculosis, Staphylococcus aureus, Salmonella enterica, and Yersiniae, in the context of the host environment. Despite the diversity of these pathogens and infection models, shared signals and responses promote recalcitrance, and common features and vulnerabilities of persisters and tolerant bacteria have emerged. These will be discussed here, along with progress toward developing therapeutic interventions to better treat recalcitrant pathogens.
抗生素耐药性通常与细菌群体内的遗传变化有关，是导致抗生素治疗失败的常见原因。抗生素的持续存在和耐受性，我们统称为抗药性，代表了细菌群体中短暂的表型变化，延长了在通常致死浓度抗生素存在下的存活时间。抗生素抗药性难以检测和研究——传统上在体外条件下进行研究，我们对其在感染期间的理解及其对抗生素失败的贡献是有限的。最近，在宿主环境背景下，包括结核分枝杆菌、金黄色葡萄球菌、肠炎沙门氏菌和耶尔森氏菌在内的致病性物种中对抗生素耐药性群体的研究取得了重大进展。尽管这些病原体和感染模型存在多样性，但共同的信号和反应促进了抗药性的产生，并且已经出现了持久性细菌和耐受细菌的共同特征和脆弱性。本文将讨论这些内容，以及朝着开发治疗干预措施以更好地治疗抗药性病原体方面取得的进展。
