De Gregorio Eliana, Esposito Anna, Vollaro Adriana, De Fenza Maria, D'Alonzo Daniele, Migliaccio Antonella, Iula Vita Dora, Zarrilli Raffaele, Guaragna Annalisa
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.
Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 80126 Naples, Italy.
Antibiotics (Basel). 2020 Jun 26;9(6):362. doi: 10.3390/antibiotics9060362.
is one of the major causes of hospital- and community-associated bacterial infections throughout the world, which are difficult to treat due to the rising number of drug-resistant strains. New molecules displaying potent activity against this bacterium are urgently needed. In this study, d- and l-deoxynojirimycin (DNJ) and a small library of their -alkyl derivatives were screened against ATCC 29213, with the aim to identify novel candidates with inhibitory potential. Among them, -nonyloxypentyl-l-DNJ (l-NPDNJ) proved to be the most active compound against ATCC 29213 and its clinical isolates, with the minimum inhibitory concentration (MIC) value of 128 μg/mL. l-NPDNJ also displayed an additive effect with gentamicin and oxacillin against the gentamicin- and methicillin-resistant isolate 00717. Sub-MIC values of l-NPDNJ affected biofilm development in a dose-dependent manner, inducing a strong reduction in biofilm biomass. Moreover, real-time reverse transcriptase PCR analysis revealed that l-NPDNJ effectively inhibited at sub-MIC values the transcription of the , , and virulence genes, as well as the and response regulator genes.
是全球医院和社区相关细菌感染的主要原因之一,由于耐药菌株数量的增加,这些感染难以治疗。迫切需要对这种细菌具有强效活性的新分子。在本研究中,针对ATCC 29213筛选了d-和l-脱氧野尻霉素(DNJ)及其小烷基衍生物文库,目的是鉴定具有抑制潜力的新候选物。其中,-壬氧基戊基-l-DNJ(l-NPDNJ)被证明是针对ATCC 29213及其临床分离株最具活性的化合物,最低抑菌浓度(MIC)值为128μg/mL。l-NPDNJ与庆大霉素和苯唑西林对庆大霉素和耐甲氧西林分离株00717也显示出相加作用。l-NPDNJ的亚MIC值以剂量依赖方式影响生物膜形成,导致生物膜生物量大幅减少。此外,实时逆转录酶PCR分析表明,l-NPDNJ在亚MIC值时有效抑制了、、和毒力基因以及和反应调节基因的转录。