Tanzawaic Acids, a Chemically Novel Set of Bacterial Conjugation Inhibitors

PLoS One. 2016 Jan 26;11(1):e0148098. doi: 10.1371/journal.pone.0148098. eCollection 2016.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus nidulans / drug effects
  • Aspergillus nidulans / genetics
  • Biological Products / chemical synthesis
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Candida albicans / drug effects
  • Candida albicans / genetics
  • Cell Line
  • Cell Survival / drug effects
  • Conjugation, Genetic / drug effects*
  • Fatty Acids, Unsaturated / chemical synthesis
  • Fatty Acids, Unsaturated / chemistry
  • Fatty Acids, Unsaturated / pharmacology*
  • HCT116 Cells
  • Humans
  • Microbial Sensitivity Tests
  • Mycobacterium smegmatis / drug effects
  • Mycobacterium smegmatis / genetics
  • Naphthalenes / chemical synthesis
  • Naphthalenes / chemistry
  • Naphthalenes / pharmacology*
  • Plasmids / genetics
  • Plasmids / metabolism

Substances

  • Biological Products
  • Fatty Acids, Unsaturated
  • Naphthalenes
  • tanzawaic acid A
  • tanzawaic acid B

Grant support

Work in the FDLC group was supported by grants BFU2014-55534-C2-1-P from the Spanish Ministry of Economy and Competitiveness (http://www.mineco.gob.es) and 612146/FP7-ICT-2013-10 and 282004/FP7-HEALTH-2011-2.3.1-2 from the European Seventh Framework Programme (https://ec.europa.eu/research/fp7). MG was supported by a PhD fellowship from the University of Cantabria (http://www.unican.es). JCG was supported by a postdoctoral fellowship ASTF 402-2010 from the European Molecular Biology Organization (http://www.embo.org). Biomar Microbial Technologies was supported by grant 282004/FP7-HEALTH-2011-2.3.1-2 from the European Seventh Framework Programme (https://ec.europa.eu/research/fp7). Biomar Microbial Technologies provided support in the form of salaries for authors JMSL, MM, and AF, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section.