Tanzawaic Acids, a Chemically Novel Set of Bacterial Conjugation Inhibitors

• Published in: PloS one Vol. 11; no. 1; p. e0148098
• Main Authors: Getino, María, Fernández-López, Raúl, Palencia-Gándara, Carolina, Campos-Gómez, Javier, Sánchez-López, Jose M, Martínez, Marta, Fernández, Antonio, de la Cruz, Fernando
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.01.2016; Public Library of Science (PLoS)
• Subjects: Acids; Antibacterial agents; Antibiotic resistance; Antibiotics; Antifungal agents; Antimicrobial agents; Aspergillus nidulans - drug effects; Aspergillus nidulans - genetics; Bacteria; Biological Products - chemical synthesis; Biological Products - chemistry; Biological Products - pharmacology; Biology and life sciences; Candida albicans - drug effects; Candida albicans - genetics; Care and treatment; Cell Line; Cell Survival - drug effects; Coins; Conjugation; Conjugation, Genetic - drug effects; E coli; Escherichia coli; Fatty acids; Fatty Acids, Unsaturated - chemical synthesis; Fatty Acids, Unsaturated - chemistry; Fatty Acids, Unsaturated - pharmacology; Fractionation; Genetic aspects; HCT116 Cells; Humans; Immunology; Incompatibility; Incp plasmids; Inhibitors; Medicine and Health Sciences; Microbial drug resistance; Microbial Sensitivity Tests; Microorganisms; Molecular biology; Mycobacterium smegmatis - drug effects; Mycobacterium smegmatis - genetics; Naphthalenes - chemical synthesis; Naphthalenes - chemistry; Naphthalenes - pharmacology; NMR; Nuclear magnetic resonance; Physical Sciences; Plasmids; Plasmids - genetics; Plasmids - metabolism; RNA polymerase; Stem cells; Toxicity; United States; Spain; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0148098

Bacterial conjugation is the main mechanism for the dissemination of multiple antibiotic resistance in human pathogens. This dissemination could be controlled by molecules that interfere with the conjugation process. A search for conjugation inhibitors among a collection of 1,632 natural compounds, identified tanzawaic acids A and B as best hits. They specially inhibited IncW and IncFII conjugative systems, including plasmids mobilized by them. Plasmids belonging to IncFI, IncI, IncL/M, IncX and IncH incompatibility groups were targeted to a lesser extent, whereas IncN and IncP plasmids were unaffected. Tanzawaic acids showed reduced toxicity in bacterial, fungal or human cells, when compared to synthetic conjugation inhibitors, opening the possibility of their deployment in complex environments, including natural settings relevant for antibiotic resistance dissemination.