Tanzawaic Acids, a Chemically Novel Set of Bacterial Conjugation Inhibitors

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,...

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Bibliographic Details
Published in:PloS one 2016-01, Vol.11 (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: Article
Language:English
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
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0148098