Tuberculosis caused by Mycobacterium tuberculosis remains a major global health concern; M. tuberculosis drug resistance and persistence further fueled the situation. Nutrient supportive therapy was intensively pursued to complement the conventional treatment, as well as their synergy with current antibiotics. To explore whether L-alanine can synergize with fluoroquinolones against M. tuberculosis, M. smegmatis was used as a surrogate in this study. We found that L-alanine can boost the bactericidal efficacy of fluoroquinolones, increasing the production of intracellular reactive oxygen species. This effect is very significant for persisters. Accelerated tricarboxylic acid cycle and/or nucleotide metabolism were observed after the addition of L-alanine. M. smegmatis MSMEG2660 is a homolog of the alanine dehydrogenase (Rv2780, MSMEG2659) negative regulator Rv2779c and involved in the L-alanine potentiation of fluoroquinolone via funneling more alanine into tricarboxylic acid. Deletion mutant of the MSMEG2660 (∆Ms2660) became more susceptible, and more readily revived from persistence. We firstly found that L-alanine can synergize with fluoroquinolones against Mycobacterium, especially the persisters via promoting metabolism. This will inspire new avenue to eliminate Mycobacterium persisters.

中文翻译：

---

L-丙氨酸可通过增加细胞内活性氧来增强氟喹诺酮类对分枝杆菌持久性的功效。

由结核分枝杆菌引起的结核病仍然是全球主要的健康问题。结核分枝杆菌的耐药性和持久性进一步加剧了这种情况。人们大力追求营养支持疗法，以补充常规疗法及其与当前抗生素的协同作用。为了探讨L-丙氨酸是否可以与氟喹诺酮类药物协同对抗结核分枝杆菌，在本研究中使用耻垢分枝杆菌作为替代。我们发现，L-丙氨酸可以增强氟喹诺酮类的杀菌功效，增加细胞内活性氧的产生。对于坚持者而言，这种效果非常重要。加入L-丙氨酸后观察到加速的三羧酸循环和/或核苷酸代谢。耻垢分枝杆菌MSMEG2660是丙氨酸脱氢酶（Rv2780，MSMEG2659）负调节剂Rv2779c，并通过将更多丙氨酸漏入三羧酸来参与氟喹诺酮的L-丙氨酸增强作用。MSMEG2660（ΔMs2660）的缺失突变体变得更易感，并且更容易从持久性中恢复过来。我们首先发现，L-丙氨酸可以与氟喹诺酮类药物协同对抗分枝杆菌，特别是通过促进代谢的持久性。这将为消除分枝杆菌的持久性提供新的途径。