Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
Front Cell Infect Microbiol. 2022 Oct 3;12:1007958. doi: 10.3389/fcimb.2022.1007958. eCollection 2022.
In the face of the unrelenting global burden of tuberculosis (TB), antibiotics remain our most effective tools to save lives and control the spread of (Mtb). However, we confront a dual challenge in our use of antibiotics: simplifying and shortening the TB drug regimen while also limiting the emergence and propagation of antibiotic resistance. This task is now more feasible due to the increasing availability of bacterial genomic data at or near the point of care. These resources create an opportunity to envision how integration of bacterial genetic determinants of antibiotic response into treatment algorithms might transform TB care. Historically, Mtb drug resistance studies focused on mutations in genes encoding antibiotic targets and the resulting increases in the minimal inhibitory concentrations (MICs) above a breakpoint value. But recent progress in elucidating the effects of functional genetic diversity in Mtb has revealed various genetic loci that are associated with drug phenotypes such as low-level MIC increases and tolerance which predict the development of resistance and treatment failure. As a result, we are now poised to advance precision medicine approaches in TB treatment. By incorporating information regarding Mtb genetic characteristics into the development of drug regimens, clinical care which tailors antibiotic treatment to maximize the likelihood of success has come into reach.
面对结核病（TB）全球负担的持续增加，抗生素仍然是挽救生命和控制（Mtb）传播的最有效工具。然而，在使用抗生素时，我们面临着双重挑战：既要简化和缩短结核病药物治疗方案，又要限制抗生素耐药性的出现和传播。由于接近护理点的细菌基因组数据的可用性不断增加，这一任务现在变得更加可行。这些资源为我们提供了一个机会，可以设想将抗生素反应的细菌遗传决定因素整合到治疗算法中，如何改变结核病的护理方式。从历史上看，Mtb 药物耐药性研究主要集中在编码抗生素靶标的基因中的突变以及由此导致的最小抑菌浓度（MIC）超过断点值的增加。但最近在阐明 Mtb 功能遗传多样性的影响方面取得的进展揭示了与药物表型相关的各种遗传基因座，例如 MIC 水平升高和耐受性的降低，这些表型预测耐药性的发展和治疗失败。因此，我们现在准备在结核病治疗中推进精准医学方法。通过将有关 Mtb 遗传特征的信息纳入药物治疗方案的制定中，我们可以实现临床护理，根据 Mtb 遗传特征调整抗生素治疗，最大限度地提高成功的可能性。
