Li Junwei, Xie Lulin, Lin Fei, Ling Baodong
Key Laboratory of Structure-Specific Small Molecule Drugs at Chengdu Medical College of Sichuan Province, School of Pharmacy, Chengdu Medical College, Chengdu, China.
Department of Pharmacy, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.
Microbiol Spectr. 2025 Apr 15;13(5):e0338824. doi: 10.1128/spectrum.03388-24.
is a critical priority gram-negative bacterial species featured with multidrug resistance and biofilm formation. This study screened 46 indole derivative agents for their antimicrobial activities against clinical isolates of extensively drug-resistant (XDRAB) with various degrees of biofilm production. Three selected indole agents-5-iodoindole, 3-methylindole, and 7-hydroxyindole-were revealed to display potent antimicrobial and antibiofilm activity, including synergistic interplay with anti-. antimicrobial drugs against XDRAB. Sub-inhibitory concentrations of these agents (particularly 7-hydroxyindole at 1/64 of MIC) not only inhibited XDRAB biofilm formation but also eradicated the mature biofilm. The survival rate of XDRAB-infected was improved with the treatment of 7-hydroxyindole. Mechanistically, 7-hydroxyindole was found to reduce the expression of quorum sensing/biofilm-implicated genes and . Together, the findings highlight the potential of indole derivatives against infections.
Extensively drug-resistant (XDRAB) isolates pose a major public health threat to antimicrobial therapy and are highly prevalent in hospital settings. This study identified and characterized indole derivative agents for their antimicrobial and antibiofilm activities against XDRAB. Sub-inhibitory indole agents such as 7-hydroxyindole can both inhibit XDRAB biofilm formation and eradicate the mature biofilm. Indole agents warrant further investigation against hard-to-treat antimicrobial-resistant pathogens.
是一种关键的优先革兰氏阴性菌,具有多重耐药性和生物膜形成能力。本研究筛选了46种吲哚衍生物对具有不同程度生物膜产生的广泛耐药鲍曼不动杆菌(XDRAB)临床分离株的抗菌活性。三种选定的吲哚试剂——5-碘吲哚、3-甲基吲哚和7-羟基吲哚——显示出强大的抗菌和抗生物膜活性,包括与抗微生物药物对XDRAB的协同相互作用。这些试剂的亚抑制浓度(特别是MIC的1/64的7-羟基吲哚)不仅抑制了XDRAB生物膜的形成,还根除了成熟生物膜。用7-羟基吲哚治疗可提高XDRAB感染的存活率。从机制上讲,发现7-羟基吲哚可降低群体感应/生物膜相关基因的表达。总之,这些发现突出了吲哚衍生物对抗感染的潜力。
广泛耐药鲍曼不动杆菌(XDRAB)分离株对抗菌治疗构成重大公共卫生威胁,且在医院环境中高度流行。本研究鉴定并表征了吲哚衍生物对XDRAB的抗菌和抗生物膜活性。亚抑制性吲哚试剂如7-羟基吲哚既能抑制XDRAB生物膜的形成,又能根除成熟生物膜。吲哚试剂值得针对难以治疗的抗菌耐药病原体进行进一步研究。