Spectrum of antibacterial activity and mode of action of a novel tris-stilbene bacteriostatic compound

Abstract The spectrum of activity and mode of action of a novel antibacterial agent, 135C, was investigated using a range of microbiological and genomic approaches. Compound 135C was active against Gram-positive bacteria with MICs for Staphylococcus aureus ranging from 0.12–0.5 μg/ml. It was largely...

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Autores principales:	Nikki Y. T. Man, Daniel R. Knight, Scott G. Stewart, Allan J. McKinley, Thomas V. Riley, Katherine A. Hammer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6225b1808d5240eb86f682657bc68d98
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spelling	oai:doaj.org-article:6225b1808d5240eb86f682657bc68d982021-12-02T16:07:51ZSpectrum of antibacterial activity and mode of action of a novel tris-stilbene bacteriostatic compound10.1038/s41598-018-25080-w2045-2322https://doaj.org/article/6225b1808d5240eb86f682657bc68d982018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25080-whttps://doaj.org/toc/2045-2322Abstract The spectrum of activity and mode of action of a novel antibacterial agent, 135C, was investigated using a range of microbiological and genomic approaches. Compound 135C was active against Gram-positive bacteria with MICs for Staphylococcus aureus ranging from 0.12–0.5 μg/ml. It was largely inactive against Gram-negative bacteria. The compound showed bacteriostatic activity in time-kill studies and did not elicit bacterial cell leakage or cell lysis. Checkerboard assays showed no synergy or antagonism when 135C was combined with a range of other antibacterials. Multi-step serial passage of four S. aureus isolates with increasing concentrations of 135C showed that resistance developed rapidly and was stable after drug-free passages. Minor differences in the fitness of 135C-resistant strains and parent wildtypes were evident by growth curves, but 135C-resistant strains did not show cross-resistance to other antibacterial agents. Genomic comparison of resistant and wildtype parent strains showed changes in genes encoding cell wall teichoic acids. 135C shows promising activity against Gram-positive bacteria but is currently limited by the rapid resistance development. Further studies are required to investigate the effects on cell wall teichoic acids and to determine whether the issue of resistance development can be overcome.Nikki Y. T. ManDaniel R. KnightScott G. StewartAllan J. McKinleyThomas V. RileyKatherine A. HammerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nikki Y. T. Man Daniel R. Knight Scott G. Stewart Allan J. McKinley Thomas V. Riley Katherine A. Hammer Spectrum of antibacterial activity and mode of action of a novel tris-stilbene bacteriostatic compound
description	Abstract The spectrum of activity and mode of action of a novel antibacterial agent, 135C, was investigated using a range of microbiological and genomic approaches. Compound 135C was active against Gram-positive bacteria with MICs for Staphylococcus aureus ranging from 0.12–0.5 μg/ml. It was largely inactive against Gram-negative bacteria. The compound showed bacteriostatic activity in time-kill studies and did not elicit bacterial cell leakage or cell lysis. Checkerboard assays showed no synergy or antagonism when 135C was combined with a range of other antibacterials. Multi-step serial passage of four S. aureus isolates with increasing concentrations of 135C showed that resistance developed rapidly and was stable after drug-free passages. Minor differences in the fitness of 135C-resistant strains and parent wildtypes were evident by growth curves, but 135C-resistant strains did not show cross-resistance to other antibacterial agents. Genomic comparison of resistant and wildtype parent strains showed changes in genes encoding cell wall teichoic acids. 135C shows promising activity against Gram-positive bacteria but is currently limited by the rapid resistance development. Further studies are required to investigate the effects on cell wall teichoic acids and to determine whether the issue of resistance development can be overcome.
format	article
author	Nikki Y. T. Man Daniel R. Knight Scott G. Stewart Allan J. McKinley Thomas V. Riley Katherine A. Hammer
author_facet	Nikki Y. T. Man Daniel R. Knight Scott G. Stewart Allan J. McKinley Thomas V. Riley Katherine A. Hammer
author_sort	Nikki Y. T. Man
title	Spectrum of antibacterial activity and mode of action of a novel tris-stilbene bacteriostatic compound
title_short	Spectrum of antibacterial activity and mode of action of a novel tris-stilbene bacteriostatic compound
title_full	Spectrum of antibacterial activity and mode of action of a novel tris-stilbene bacteriostatic compound
title_fullStr	Spectrum of antibacterial activity and mode of action of a novel tris-stilbene bacteriostatic compound
title_full_unstemmed	Spectrum of antibacterial activity and mode of action of a novel tris-stilbene bacteriostatic compound
title_sort	spectrum of antibacterial activity and mode of action of a novel tris-stilbene bacteriostatic compound
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/6225b1808d5240eb86f682657bc68d98
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Spectrum of antibacterial activity and mode of action of a novel tris-stilbene bacteriostatic compound

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