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Investigation of In-Vitro Adaptation toward Sodium Bituminosulfonate in Staphylococcus aureus.

ABSTRACT: The global increase in antimicrobial resistance has revived the interest in "old" substances with antimicrobial activity such as sodium bituminosulfonate. However, for those "old" compounds, scientific studies are still sparse and the ones available do not mostly meet the current standards. Since this compound is used for topical applications, investigation of a potential increase in minimal inhibitory concentrations (MICs) is of particular importance. For selection of phenotypes with decreased susceptibility, a collection of 30 genetically diverse methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) strains were cultured on bi-layered linear gradient agar plates containing sub-inhibitory concentrations of the active agents. The stability of phenotypes with increased MICs was determined by serial passage on agent-free medium. Within 10 passages, only slight and, in most cases, reversible increases in MSSA and MRSA MIC levels toward sodium bituminosulfonate were obtained. Fusidic acid, used as a control, showed exponential expansions in MIC based on mutations in the fusA gene (elongation factor G or EF-G) with no reduction during the recovery phase. The only marginal and largely reversible changes of S. aureus MICs after exposition to sodium bituminosulfonate indicate a low potential for resistance development.

SUBMITTER: Blisse M

PROVIDER: S-EPMC7763802 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Investigation of In-Vitro Adaptation toward Sodium Bituminosulfonate in <i>Staphylococcus aureus</i>.

Blisse Marko M Idelevich Evgeny A EA Becker Karsten K

Microorganisms 20201210 12

The global increase in antimicrobial resistance has revived the interest in "old" substances with antimicrobial activity such as sodium bituminosulfonate. However, for those "old" compounds, scientific studies are still sparse and the ones available do not mostly meet the current standards. Since this compound is used for topical applications, investigation of a potential increase in minimal inhibitory concentrations (MICs) is of particular importance. For selection of phenotypes with decreased ...[more]

PMID: 33322073

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Project description:Skin is the most common site of Staphylococcus aureus infection. While most of these infections are self-limited, recurrent infections are common. Keratinocytes and recruited immune cells participate in skin defense against infection. We postulated that S. aureus is able to adapt to the milieu within human keratinocytes to avoid keratinocyte-mediated clearance. From a collection of S. aureus isolated from chronically infected patients with atopic dermatitis, we noted 22% had an agr mutant-like phenotype. Using several models of human skin infection, we demonstrate that toxin-deficient, agr mutants of methicillin-resistant S. aureus (MRSA) USA300 are able to persist within keratinocytes by stimulating autophagy and evading caspase-1 and inflammasome activation. MRSA infection induced keratinocyte autophagy, as evidenced by galectin-8 and LC3 accumulation. Autophagy promoted the degradation of inflammasome components and facilitated staphylococcal survival. The recovery of more than 58% agr or RNAIII mutants (P < 0.0001) of an inoculum of wild-type (WT) MRSA from within wortmannin-treated keratinocytes compared to control keratinocytes reflected the survival advantage for mutants no longer expressing agr-dependent toxins. Our results illustrate the dynamic interplay between S. aureus and keratinocytes that can result in the selection of mutants that have adapted specifically to evade keratinocyte-mediated clearance mechanisms. Human skin is a major site of staphylococcal infection, and keratinocytes actively participate in eradication of these pathogens. We demonstrate that methicillin-resistant Staphylococcus aureus (MRSA) is ingested by keratinocytes and activates caspase-1-mediated clearance through pyroptosis. Toxin-deficient MRSA mutants are selected within keratinocytes that fail to induce caspase-1 activity and keratinocyte-mediated clearance. These intracellular staphylococci induce autophagy that enhances their intracellular survival by diminishing inflammasome components. These findings suggest that S. aureus mutants, by exploiting autophagy, can persist within human keratinocytes.

Dataset Information

Investigation of In-Vitro Adaptation toward Sodium Bituminosulfonate in Staphylococcus aureus.

Publications

Investigation of In-Vitro Adaptation toward Sodium Bituminosulfonate in <i>Staphylococcus aureus</i>.

Similar Datasets

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