Increased drug resistance of meticillin-resistant Staphylococcus aureus biofilms formed on a mouse dermal chip model

Abstract

PurposeMeticillin-resistant Staphylococcus aureus (MRSA) biofilm formation in humans is of serious clinical concern. Previous in vitro studies have been performed with biofilms grown only on inorganic substrates; therefore, we investigated the vancomycin (VCM) resistance of MRSA biofilms grown on skin tissue.MethodologyWe established a novel tissue substrate model, namely MRSA grown on segments of mouse skin tissue (dermal chips, DCs), and compared its resistance capacity against VCM with that of MRSA biofilms grown on plastic chips (PCs).Results/Key findingsFor one MRSA isolate, we found that the VCM MIC was identical (1.56 µg ml−1) for planktonic cultures and for biofilms-formed on PCs (PC-BF), although the minimum bactericidal concentration (MBC) increased to 6.25 µg ml−1 in PC-BF. On the contrary, the MIC and MBC for biofilms formed on DCs (DC-BF) significantly increased (25 and 50 µg ml−1, respectively). Furthermore, the minimum biofilm-eradicating concentration was higher for DC-BF (100 µg ml−1) than for PC-BF (25 µg ml−1). Using six MRSA strains, we found that in PC-BF, the c.f.u. number decreased with increasing VCM concentration, whereas in DC-BF, it greatly increased until the MIC was reached, accompanied by the formation of large colonies, thicker bacterial walls and the presence of many mitotic cells.ConclusionOur results indicate that the VCM resistance of MRSA was greater in DC-BF. We conclude that DCs may provide a specific environment for MRSA that enhances bacterial growth under cytotoxic VCM concentrations, and might be useful for the study of skin wound infections and the effects of antimicrobial drugs.

Inhibitory effects of polysorbate 80 on MRSA biofilm formed on different substrates including dermal tissue

“…Biofilms are frequently developed in ulcerative wounded tissues. We thus examined the tissue substrate using a novel mouse dermal chip, which was established in our previous study 25 . Compared to the plastic substrate, MRSA showed greater attachment to the dermal tissue surface, and PS80 prevented bacterial attachment to plastic as well as dermal tissue.…”

“…The preparation of mouse dermal chips has been described previously 25 . All animal experiments received prior approval from the animal experiment approval committee of Fukuoka University Animal Center (approval number 1210608).…”

Fatty Acid Potassium Had Beneficial Bactericidal Effects and Removed Staphylococcus aureus Biofilms while Exhibiting Reduced Cytotoxicity towards Mouse Fibroblasts and Human Keratinocytes

“…Therefore, biofilm production by multiple clinically important bacterial strains is significantly associated with persistent wound infections [17]. A type of MRSA (ATCC, BAA-2856; formerly named OJ-1) that we isolated from a clinical sample exhibited increased resistance to vancomycin in a mouse dermal chip model [18,19]. In addition, it was highly capable of producing highly virulent biofilms, and was able to survive in mouse Kupffer cells [20].…”

The Effects of Silver Sulfadiazine on Methicillin-Resistant Staphylococcus aureus Biofilms

“…ATCC BAA-2856 (OJ-1) [ 34 , 35 , 36 ], a high-BF-forming strain of MRSA, was used. BF chips were prepared as previously described [ 36 , 37 ]. In brief, one colony grown on tryptic soy agar (TSA) was inoculated in tryptic soy broth (TSB) and grown at 37 °C until the optical density (OD) = 0.57 (λ = 578 nm).…”

“…The minimum antibacterial concentrations of compounds for bacteria derived from BF were determined by methods described previously [ 37 ] with some modifications ( Figure S1 ). After incubating the bacteria for 24 h with different compounds at different concentrations, the culture tubes were kept at 4 °C for 1 h in order for the compounds to sediment, before the turbidity in the supernatant was measured (λ = 578 nm).…”