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Title: Nusbiarylins inhibit transcription and target virulence factors in bacterial pathogen staphylococcus aureus
Authors: Chu, AJ
Qiu, Y 
Harper, R
Lin, L
Ma, C 
Yang, X
Issue Date: 11-Aug-2020
Source: International journal of molecular sciences, 11 Aug. 2020, v. 21, no. 16, 5772, p. 1-18
Abstract: The emergence of multidrug resistance in the clinically significant pathogen Staphylococcus aureus is a global health burden, compounded by a diminishing drug development pipeline, and a lack of approved novel antimicrobials. Our previously reported first-in-class bacterial transcription inhibitors “nusbiarylins” presented a promising prospect towards the discovery of novel antimicrobial agents with a novel mechanism. Here we investigated and characterised the lead nusbiarylin compound, MC4, and several of its chemical derivatives in both methicillin-resistant S. aureus (MRSA) and the S. aureus type strains, demonstrating their capacity for the arrest of growth and cellular respiration, impairment of RNA and intracellular protein levels at subinhibitory concentrations. In some instances, derivatives of MC4 were also shown to attenuate the production of staphylococcal virulence factors in vitro, such as the exoproteins α-toxin and Panton–Valentine Leukocidin (PVL). Trends observed from quantitative PCR assays suggested that nusbiarylins elicited these effects possibly by acting via but not limited to the modulation of global regulatory pathways, such as the agr regulon, which coordinates the expression of S. aureus genes associated with virulence. Our findings encourage the continued development of more potent compounds within this novel family of bacterial transcription inhibitors.
Keywords: Antibiotic
Antimicrobial agent
Drug discovery
MRSA
Nusbiarylin
Staphylococcus aureus
Publisher: Molecular Diversity Preservation International (MDPI)
Journal: International journal of molecular sciences 
ISSN: 1661-6596
EISSN: 1422-0067
DOI: 10.3390/ijms21165772
Rights: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
The following publication Chu AJ, Qiu Y, Harper R, Lin L, Ma C, Yang X. Nusbiarylins Inhibit Transcription and Target Virulence Factors in Bacterial Pathogen Staphylococcus aureus. International Journal of Molecular Sciences. 2020; 21(16):5772, is available at https://doi.org/10.3390/ijms21165772
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