title: Combating multidrug resistance in bacterial infection by targeting functional proteome with natural products.
abstract: Antibiotic resistance has become a major clinical and public health problem within the lifetime of most people living today. Development of new therapeutic approaches to prevent antimicrobial chemotherapy from bacterial multidrug resistance has thus been becoming a primary consideration in the medicinal community. In this study, we describe a protocol that is potential for combating multidrug resistance by rational screening of natural medicines to target the bacterial functional proteome. To achieve this, a pipeline of integrating virtual screening and susceptibility testing has been described to identify antibacterial agents from various natural products with diverse structures and high drug-likeness. A number of promising candidates with potent antibacterial activity were identified, from which six available compounds were assayed to determine their susceptibility to four multidrug-resistant strains. Consequently, while most tested candidates showed moderate (20 < MIC < 50 μg/mL) or low (MIC>50 μg/mL) antibacterial activities, two natural products, i.e. pseudopterosin A and ciprofloxacin, were measured to possess strong broad-spectrum potency combating different strains (MIC < 20 μg/mL).
authors.affiliation: a Department of Burn and Plastic Surgery , Zhongda Hospital Southeast University , No. 87 Dingjiaqiao Rd, Nanjing 210009 , P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xiong
authors.forename: Zongke
authors.initials: Z
authors.lastname: Guo
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001688:Biological Products / Q000737:chemistry*; D020134:Catalytic Domain; D002939:Ciprofloxacin / Q000737:chemistry; D004224:Diterpenes / Q000737:chemistry; D024901:Drug Resistance, Multiple, Bacterial; D006027:Glycosides / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D020543:Proteome
chemical_list: D000900:Anti-Bacterial Agents; D001688:Biological Products; D004224:Diterpenes; D006027:Glycosides; D020543:Proteome; C049922:pseudopterosins; D002939:Ciprofloxacin
keywords: functional proteome; infection; multidrug resistance; natural medicine