Liu Chang, Cui Chenxuan, Tan Xiaoxin, Miao Junjie, Wang Wei, Ren Han, Wu Hua, Zheng Cuiying, Ren Huan, Kang Weijun
School of Public Health, Hebei Medical University, Shijiazhuang, China.
Shijiazhuang Qiaoxi Distinct Center for Disease Control and Prevention, Shijiazhuang, China.
Front Microbiol. 2024 Sep 24;15:1464719. doi: 10.3389/fmicb.2024.1464719. eCollection 2024.
The emergence of multidrug-resistant isolates is a growing concern for public health, necessitating new therapeutic strategies. Gallium nitrate [Ga(NO)], a medication for cancer-related hypercalcemia, has attracted great attention due to its ability to inhibit growth and biofilm formation by disrupting iron metabolism. However, the antibacterial efficacy of Ga(NO) is not always satisfactory. It is imperative to investigate the factors that affect the bactericidal effects of Ga(NO) and to identify new ways to enhance its efficacy. This study focused on the impact of pH on resistance to Ga(NO), along with the underlying mechanism. The results indicate that acidic conditions could increase the effectiveness of Ga(NO) against by promoting the production of pyochelin and gallium uptake. Subsequently, using glutamic acid, a clinically compatible acidic amino acid, the pH was significantly lowered and enhanced the bactericidal and inhibitory efficacy of Ga(NO) against biofilm formation by , including a reference strain PA14 and several multidrug-resistant clinical isolates. Furthermore, we used an abscess mouse model to evaluate this combination ; the results show that the combination of glutamic acid and Ga(NO) significantly improved clearance. Overall, the present study demonstrates that acidic conditions can increase the sensitivity of to Ga(NO). Combining glutamic acid and Ga(NO) is a potential strategy for the treatment of infections.
多重耐药菌株的出现日益引起公共卫生领域的关注，因此需要新的治疗策略。硝酸镓[Ga(NO)]是一种用于治疗癌症相关高钙血症的药物，因其能够通过干扰铁代谢来抑制细菌生长和生物膜形成而备受关注。然而，Ga(NO)的抗菌效果并不总是令人满意。研究影响Ga(NO)杀菌效果的因素并找到提高其疗效的新方法势在必行。本研究聚焦于pH值对Ga(NO)耐药性的影响及其潜在机制。结果表明，酸性条件可通过促进绿脓菌素的产生和镓的摄取来提高Ga(NO)对（细菌）的有效性。随后，使用谷氨酸（一种临床适用的酸性氨基酸）显著降低了pH值，并增强了Ga(NO)对包括参考菌株PA14和几种多重耐药临床分离株在内的（细菌）生物膜形成的杀菌和抑制效果。此外，我们使用脓肿小鼠模型来评估这种联合（用药）；结果表明，谷氨酸和Ga(NO)的联合用药显著提高了（细菌）清除率。总体而言，本研究表明酸性条件可增加（细菌）对Ga(NO)的敏感性。联合使用谷氨酸和Ga(NO)是治疗（细菌）感染的一种潜在策略。
