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dc.contributor.authorWeaver, Alan J.
dc.contributor.authorPeters, Tami R.
dc.contributor.authorTripet, Brian P.
dc.contributor.authorVan Vuren, Abigail
dc.contributor.authorRakesh
dc.contributor.authorLee, Richard E.
dc.contributor.authorCopie, Valerie
dc.contributor.authorTeintze, Martin
dc.date.accessioned2018-11-19T17:59:00Z
dc.date.available2018-11-19T17:59:00Z
dc.date.issued2018-06
dc.identifier.citationWeaver, Alan J. , Tami R. Peters, Brian Tripet, Abigail Van Vuren, Richard E. Lee Rakesh, Valerie Copie, and Martin Teintze. Exposure of Methicillin-Resistant Staphylococcus aureus to Low Levels of the Antibacterial THAM-3ΦG Generates a Small Colony Drug-Resistant Phenotype." Scientific Reports 8 (June 2018): 1-14. DOI:10.1038/s41598-018-28283-3.en_US
dc.identifier.issn2045-2322
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/15021
dc.description.abstractThis study investigated resistance against trishexylaminomelamine trisphenylguanide (THAM-3ΦG), a novel antibacterial compound with selective microbicidal activity against Staphylococcus aureus. Resistance development was examined by culturing methicillin resistant S. aureus (MRSA) with sub-lethal doses of THAM-3ΦG. This quickly resulted in the formation of normal (WT) and small colonies (SC) of S. aureus exhibiting minimal inhibitory concentrations (MICs) 2× and 4× greater than the original MIC. Continuous cell passaging with increasing concentrations of THAM-3ΦG resulted in an exclusively SC phenotype with MIC >64 mg/L. Nuclear magnetic resonance (NMR)-based metabolomics and multivariate statistical analysis revealed three distinct metabolic profiles for THAM-3ΦG treated WT, untreated WT, and SC (both treated and untreated). The metabolome patterns of the SC sample groups match those reported for other small colony variants (SCV) of S. aureus. Supplementation of the SCV with menadione resulted in almost complete recovery of growth rate. This auxotrophism was corroborated by NMR analysis revealing the absence of menaquinone production in the SCV. In conclusion, MRSA rapidly acquires resistance to THAM-3ΦG through selection of a slow-growing menaquinone auxotroph. This study highlights the importance of evaluating and monitoring resistance to novel antibacterials during development.en_US
dc.description.sponsorshipSt Jude Children's Research Hospital; Montana Research Initiative (51040-MUSRI2015-03); National Institutes of Health; National Science Foundation; Murdock Charitable Trusten_US
dc.language.isoenen_US
dc.rightsCCBY, This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcodeen_US
dc.titleExposure of Methicillin-Resistant Staphylococcus aureus to Low Levels of the Antibacterial THAM-3ΦG Generates a Small Colony Drug-Resistant Phenotypeen_US
dc.typeArticleen_US
mus.citation.extentfirstpage1en_US
mus.citation.extentlastpage14en_US
mus.citation.journaltitleScientific Reportsen_US
mus.citation.volume8en_US
mus.identifier.categoryChemical & Material Sciencesen_US
mus.identifier.doi10.1038/s41598-018-28283-3en_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentChemistry & Biochemistry.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.data.thumbpage6en_US
mus.contributor.orcidCopie, Valerie|0000-0002-2778-1463en_US


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CCBY, This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.
Except where otherwise noted, this item's license is described as CCBY, This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.

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