title: Tanzawaic Acids, a Chemically Novel Set of Bacterial Conjugation Inhibitors.
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.
authors.affiliation: Instituto de Biomedicina y Biotecnología de Cantabria, Universidad de Cantabria-Consejo Superior de Investigaciones Científicas, Santander, Cantabria, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Getino
authors.affiliation: Instituto de Biomedicina y Biotecnología de Cantabria, Universidad de Cantabria-Consejo Superior de Investigaciones Científicas, Santander, Cantabria, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Fernández-López
authors.affiliation: Instituto de Biomedicina y Biotecnología de Cantabria, Universidad de Cantabria-Consejo Superior de Investigaciones Científicas, Santander, Cantabria, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Palencia-Gándara
authors.affiliation: Instituto de Biomedicina y Biotecnología de Cantabria, Universidad de Cantabria-Consejo Superior de Investigaciones Científicas, Santander, Cantabria, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Campos-Gómez
authors.affiliation: Biomar Microbial Technologies, Armunia, León, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Sánchez-López
authors.affiliation: Biomar Microbial Technologies, Armunia, León, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Martínez
authors.affiliation: Biomar Microbial Technologies, Armunia, León, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernández
authors.affiliation: Instituto de Biomedicina y Biotecnología de Cantabria, Universidad de Cantabria-Consejo Superior de Investigaciones Científicas, Santander, Cantabria, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: de la Cruz
mesh_terms: D001233:Aspergillus nidulans / Q000187:drug effects / Q000235:genetics; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003227:Conjugation, Genetic / Q000187:drug effects*; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000235:genetics; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010957:Plasmids / Q000235:genetics / Q000378:metabolism
chemical_list: D001688:Biological Products; D005231:Fatty Acids, Unsaturated; D009281:Naphthalenes; C000609259:tanzawaic acid A; C000609260:tanzawaic acid B
references.citation: Org Biomol Chem. 2015 Jul 14;13(26):7248-56
references.pmid: 26055397
references.citation: J Antimicrob Chemother. 2009 Sep;64 Suppl 1:i3-10
references.pmid: 19675017
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12282-7
references.pmid: 17630285
references.citation: Philos Trans R Soc Lond B Biol Sci. 2009 Aug 12;364(1527):2275-89
references.pmid: 19571247
references.citation: J Sci Food Agric. 2013 Mar 30;93(5):1134-9
references.pmid: 22936522
references.citation: Antimicrob Agents Chemother. 1982 Nov;22(5):805-9
references.pmid: 7181490
references.citation: Mol Microbiol. 2007 Jan;63(2):404-16
references.pmid: 17163977
references.citation: Antimicrob Agents Chemother. 2009 Jun;53(6):2227-38
references.pmid: 19307361
references.citation: J Immunol Methods. 1986 May 22;89(2):271-7
references.pmid: 3486233
references.citation: J Bacteriol. 1970 Dec;104(3):1273-9
references.pmid: 16559103
references.citation: Biol Reprod. 2003 Jun;68(6):2150-6
references.pmid: 12606388
references.citation: Biochim Biophys Acta. 2014 Aug;1843(8):1578-91
references.pmid: 24389247
references.citation: Nat Protoc. 2008;3(2):163-75
references.pmid: 18274517
references.citation: Biochem Biophys Res Commun. 2005 Dec 9;338(1):668-76
references.pmid: 16126168
references.citation: Phytochemistry. 2000 Jun;54(3):301-9
references.pmid: 10870185
references.citation: PLoS One. 2011;6(5):e19991
references.pmid: 21637841
references.citation: Antimicrob Agents Chemother. 2011 Aug;55(8):3649-60
references.pmid: 21576439
references.citation: Bioorg Med Chem Lett. 2012 Oct 1;22(19):6185-9
references.pmid: 22932312
references.citation: Lipids. 2006 May;41(5):507-11
references.pmid: 16933795
references.citation: PLoS Genet. 2014 Feb;10(2):e1004171
references.pmid: 24586200
references.citation: Magn Reson Imaging. 1994;12(3):477-86
references.pmid: 8007778
references.citation: Beilstein J Org Chem. 2014 Jan 22;10:251-8
references.pmid: 24605144
references.citation: J Cell Physiol. 1979 Apr;99(1):43-54
references.pmid: 222778
references.citation: Br J Cancer. 1996 Mar;73(5):596-602
references.pmid: 8605092
references.citation: J Immunol Methods. 1983 Dec 16;65(1-2):55-63
references.pmid: 6606682
references.citation: J Gen Microbiol. 1980 Feb;116(2):475-84
references.pmid: 6989956
references.citation: Science. 2006 May 19;312(5776):1044-6
references.pmid: 16645050
references.citation: Chem Biol. 2006 Mar;13(3):297-307
references.pmid: 16638535
references.citation: Proc Natl Acad Sci U S A. 1990 Jun;87(12):4645-9
references.pmid: 2162051
references.citation: Int J Cancer. 1976 Jan 15;17(1):62-70
references.pmid: 175022
references.citation: MBio. 2015;6(5):e01032-15
references.pmid: 26330514
references.citation: Bioorg Med Chem Lett. 2014 Dec 15;24(24):5787-91
references.pmid: 25453820
references.citation: J Mol Biol. 1986 May 5;189(1):113-30
references.pmid: 3537305
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):127-32
references.pmid: 20007769
references.citation: Microbiology. 2005 Nov;151(Pt 11):3517-26
references.pmid: 16272375
references.citation: Clin Infect Dis. 2009 Jan 1;48(1):1-12
references.pmid: 19035777
references.citation: Chem Phys Lipids. 2014 Feb;178:84-91
references.pmid: 24365283
references.citation: Scand J Immunol. 1984 Aug;20(2):97-104
references.pmid: 6206556
references.citation: Biochem Biophys Res Commun. 2012 Aug 10;424(4):697-703
references.pmid: 22796221
references.citation: Bioorg Med Chem. 2010 Nov 1;18(21):7475-85
references.pmid: 20855214
references.citation: Can J Microbiol. 1978 May;24(5):593-7
references.pmid: 26458