Abstract

Staphylococcus epidermidis cleanroom strains are often exposed to sub-inhibitory concentrations of disinfectants, including didecyldimethylammonium chloride (DDAC). Consequently, they can adapt or even become tolerant to them. RNA-sequencing was used to investigate adaptation and tolerance mechanisms of S. epidermidis cleanroom strains (SE11, SE18), with S. epidermidis SE11Ad adapted and S. epidermidis SE18To tolerant to DDAC. Adaptation to DDAC was identified with up-regulation of genes mainly involved in transport (thioredoxin reductase [pstS], the arsenic efflux pump [gene ID, SE0334], sugar phosphate antiporter [uhpT]), while down-regulation was seen for the Agr system (agrA, arC, agrD, psm, SE1543), for enhanced biofilm formation. Tolerance to DDAC revealed the up-regulation of genes associated with transporters (L-cysteine transport [tcyB]; uracil permease [SE0875]; multidrug transporter [lmrP]; arsenic efflux pump [arsB]); the down-regulation of genes involved in amino-acid biosynthesis (lysine [dapE]; histidine [hisA]; methionine [metC]), and an enzyme involved in peptidoglycan, and therefore cell wall modifications (alanine racemase [SE1079]). We show for the first time the differentially expressed genes in DDAC-adapted and DDAC-tolerant S. epidermidis strains, which highlight the complexity of the responses through the involvement of different mechanisms.

Highlights

  • Staphylococcus epidermidis is a member of the coagulase-negative Staphylococcus group, and it is the most common bacterial species of human skin and mucosa [1,2,3]

  • We suggest that up−regulation of the tcyB gene that is involved in the uptake of L−cysteine is an important adaptation and tolerance mechanism for maintenance of cellular homeostasis in both SE11Ad and SE18To

  • Biofilm formation protects cells from the harmful effects of antimicrobials as this limits the diffusion into the cells, and so a shift to biofilm production is one of the adaptation response mechanisms. This analysis of the transcriptomes of these didecyldimethylammonium chloride (DDAC)−adapted (SE11Ad) and DDAC−tolerant (SE18To) S. epidermidis strains revealed for the first time the most significant genes, and mechanisms, that are involved in the adaptation and tolerance responses of S. epidermidis to this commonly used disinfectant

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Summary

Introduction

Staphylococcus epidermidis is a member of the coagulase-negative Staphylococcus group, and it is the most common bacterial species of human skin and mucosa [1,2,3]. S. epidermidis strains are known to adapt to different environmental changes. The presence of low concentrations of disinfectants will provide the opportunity for these bacteria to adapt and/or to develop tolerance [6,7]. S. epidermidis strains are one of the most common cleanroom isolates. Cleanrooms are places that are considered to be microbially reduced environments [8] with defined and controlled air quality (e.g., generally using high-efficiency particulate air-filtration systems), particles in the air, temperature and humidity. Cleanrooms ensure the quality and safety of many production areas, where contamination with microorganisms and particles is critical, such as in surgical units, manufacture of pharmaceuticals, food production and biosafety laboratories [8,9]. Disinfection of cleanrooms is a common procedure that is very important for maintenance of low levels of microbial burden

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