Abstract：
Some naturally occurring compounds, known for their antimicrobial activities, have been employed as food additives. However, their efficacy in treating infections caused by antibiotic-resistant bacteria is yet to be fully explored. Rapidly growing mycobacteria (RGM), a category within nontuberculous mycobacteria (NTM), are prevalent in various environments and can lead to infections in humans. The rise of antimicrobial resistance within RGM is a documented concern. In this study, we reported that four specific natural compounds effectively inhibited the growth and biofilm formation of three key RGM pathogens M. abscessus, M. fortuitum, and M. chelonae. We screened 12 natural compounds for their effectiveness against antibiotic-resistant clinical strains of RGM. Four compounds showed significant inhibitory effects from the most effective to least: trans-cinnamaldehyde, carvacrol, gentisaldehyde, and phloroglucinaldehyde. In the analysis of time-killing kinetics, gentisaldehyde and phloroglucinaldehyde displayed bactericidal activity while trans-cinnamaldehyde and carvacrol exhibited bacteriostatic effects. At 1× minimal inhibition concentrations, these compounds significantly reduced biofilm formation in all three RGM species to levels between 2.9% and 20.5% relative to controls. Checkerboard assays indicated synergistic interactions between these four compounds and antibiotics such as amikacin, clarithromycin, and linezolid. Of these 12 compound-antibiotic combinations, the pairs of carvacrol-linezolid, carvacrol-amikacin, and gentisaldehyde-clarithromycin demonstrated the most synergy against multiple RGM strains. Moreover, two other compounds citral and geraniol showed synergism with all three test antibiotics. Time-killing assays further confirmed most of synergistic combinations identified in the checkerboard tests. Our research suggests the potential of these essential oils and phenolic aldehydes, both individually and in combination with antibiotics, in treating RGM infections. In addition, this work illuminates applications of these natural compounds in environmental remediation to mitigate bacterial persistence for the control of infectious diseases.
OBJECTIVE: The emergence of antimicrobial resistance within rapidly growing mycobacteria (RGM) poses a significant threat to public health. This study investigates the potential of naturally occurring compounds to combat infections caused by antibiotic-resistant RGM including M. abscessus, M. fortuitum, and M. chelonae. We identified four specific natural compounds showing impressive inhibitory effects against antibiotic-resistant clinical strains. These compounds not only inhibited the growth and biofilm formation but also exhibited synergistic interactions with antibiotics against key RGM pathogens. Our findings highlight the alternative treatment strategies for RGM infections and potential environmental applications of these natural compounds in mitigating microbial persistence and controlling infectious diseases.
OBJECTIVE: The emergence of antimicrobial resistance within rapidly growing mycobacteria (RGM) poses a significant threat to public health. This study investigates the potential of naturally occurring compounds to combat infections caused by antibiotic-resistant RGM including M. abscessus, M. fortuitum, and M. chelonae. We identified four specific natural compounds showing impressive inhibitory effects against antibiotic-resistant clinical strains. These compounds not only inhibited the growth and biofilm formation but also exhibited synergistic interactions with antibiotics against key RGM pathogens. Our findings highlight the alternative treatment strategies for RGM infections and potential environmental applications of these natural compounds in mitigating microbial persistence and controlling infectious diseases.
摘要：
一些天然存在的化合物，以其抗菌活性而闻名，已被用作食品添加剂。然而,它们在治疗由抗生素耐药性细菌引起的感染方面的功效尚未得到充分探索。快速增长的分枝杆菌（RGM），非结核分枝杆菌（NTM）中的一类，在各种环境中普遍存在，并可能导致人类感染。RGM中抗菌素耐药性的上升是一个记录在案的问题。在这项研究中,我们报道了四种特定的天然化合物有效地抑制了三种关键的RGM病原体的生长和生物膜的形成。M.偶然性，和M.chelonae。我们筛选了12种天然化合物对RGM的抗生素抗性临床菌株的有效性。从最有效到最不有效的四种化合物显示出显着的抑制作用：反式肉桂醛，香芹酚,龙胆乙醛，和间苯三酚醛.在计时动力学分析中，龙胆醛和间苯三酚醛具有杀菌活性，而反式肉桂醛和香芹酚具有抑菌作用。在1×最小抑制浓度下，相对于对照,这些化合物显著降低了所有三种RGM物种的生物膜形成至2.9%至20.5%的水平.棋盘分析表明这四种化合物与抗生素如阿米卡星之间的协同相互作用，克拉霉素,和利奈唑胺.在这12种复合抗生素组合中，香芹酚-利奈唑胺成对,香芹酚-阿米卡星,和龙胆醛-克拉霉素对多种RGM菌株表现出最大的协同作用。此外，另外两种化合物柠檬醛和香叶醇显示出与所有三种测试抗生素的协同作用。时间消逝测定进一步证实了棋盘测试中鉴定的大多数协同组合。我们的研究表明这些精油和酚醛的潜力，无论是单独还是与抗生素联合使用，治疗RGM感染。此外,这项工作阐明了这些天然化合物在环境修复中的应用，以减轻细菌的持久性，从而控制传染病。
目的：快速生长的分枝杆菌（RGM）中抗菌药物耐药性的出现对公众健康构成了重大威胁。这项研究调查了天然化合物对抗抗生素耐药性RGM引起的感染的潜力，包括脓肿分枝杆菌，M.偶然性，和M.chelonae。我们确定了四种特定的天然化合物，它们对抗生素抗性临床菌株具有令人印象深刻的抑制作用。这些化合物不仅抑制生长和生物膜形成,而且还表现出与抗生素对抗关键RGM病原体的协同相互作用。我们的发现强调了RGM感染的替代治疗策略以及这些天然化合物在减轻微生物持久性和控制传染病方面的潜在环境应用。
目的：快速生长的分枝杆菌（RGM）中抗菌药物耐药性的出现对公众健康构成了重大威胁。这项研究调查了天然化合物对抗抗生素耐药性RGM引起的感染的潜力，包括脓肿分枝杆菌，M.偶然性，和M.chelonae。我们确定了四种特定的天然化合物，它们对抗生素抗性临床菌株具有令人印象深刻的抑制作用。这些化合物不仅抑制生长和生物膜形成,而且还表现出与抗生素对抗关键RGM病原体的协同相互作用。我们的发现强调了RGM感染的替代治疗策略以及这些天然化合物在减轻微生物持久性和控制传染病方面的潜在环境应用。
