Lacoma, AliciaAliciaLacomaEdwards, Andrew MAndrew MEdwardsYoung, Bernadette CBernadette CYoungDominguez, JoseJoseDominguezPrat, CristinaCristinaPratLaabei, MaisemMaisemLaabei2020-10-222020-10-222019-07-25Scientific Reports, 2019, 9, pp.1-152045-2322http://hdl.handle.net/10044/1/83362Tobacco smoking represents the leading preventable cause of death worldwide. Smoking is a recognised risk factor for several pathologies and is detrimental to host immune surveillance and defence. However, the impact of smoking on microbial residents of the nasopharyngeal cavity, in contact with cigarette smoke (CS), is lacking. Staphylococcus aureus is a major human pathogen that colonises the human nasopharynx and causes a wide range of infections. We investigated the impact of CS on specific virulence phenotypes important in S aureus pathogenesis. We observed strain-dependent differences following exposure to CS, namely growth inhibition, augmented biofilm formation, increased invasion of, and persistence within, bronchial alveolar epithelial cells. Additionally, we confirm the critical role of a functional accessory gene regulator (Agr) system in mediating increased biofilm development and host cell invasion and persistence following CS exposure. Furthermore, CS exposure resulted in reduced toxin production. Importantly, exposure of S aureus to CS accelerated the frequency of mutations and resulted in a significant increase in gentamicin-resistant small colony variant (SCV) formation. Mutational analysis revealed that CS induced SCVs emerge via the SOS response DNA mutagenic repair system. Taken together, our results suggest that CS redirects certain S aureus strains to a virulence profile associated with persistence.© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Science & TechnologyMultidisciplinary SciencesScience & Technology - Other TopicsSMALL-COLONY VARIANTSBIOFILM FORMATIONNASAL CARRIAGESTREPTOCOCCUS-PNEUMONIAEOXIDATIVE STRESSTOBACCO SMOKINGRISK-FACTORSCELL-WALLCOLONIZATIONGENOMEJournal Articlehttps://www.dx.doi.org/10.1038/s41598-019-47258-6https://www.nature.com/articles/s41598-019-47258-6MR/P028225/1