Staphylococcus aureus small-colony variants: Formation, infection, and treatment.

Background Florfenicol might be ineffective for treating Staphylococcus aureus small colony variants (SCVs) mastitis. Objectives In this study, florfenicol-loaded chitosan (CS)-sodium tripolyphosphate (TPP) composite nanogels were prepared to allow targeted delivery to SCV infected sites. Methods The formulation screening, the characteristics, in vitro release, antibacterial activity, therapeutic efficacy, and biosafety of the florfenicol composite nanogels were studied. Results The optimized formulation was obtained when the CS and TPP were 10 and 5 mg/mL, respectively. The encapsulation efficiency, loading capacity, size, polydispersity index, and zeta potential of the optimized florfenicol composite nanogels were 87.3% ± 2.7%, 5.8% ± 1.4%, 280.3 ± 1.5 nm, 0.15 ± 0.03, and 36.3 ± 1.4 mv, respectively. Optical and scanning electron microscopy showed that spherical particles with a relatively uniform distribution and drugs might be incorporated in cross-linked polymeric networks. The in vitro release study showed that the florfenicol composite nanogels exhibited a biphasic pattern with the sustained release of 72.2% ± 1.8% at 48 h in pH 5.5 phosphate-buffered saline. The minimal inhibitory concentrations of commercial florfenicol solution and florfenicol composite nanogels against SCVs were 1 and 0.25 µg/mL, respectively. The time-killing curves and live–dead bacterial staining showed that the florfenicol composite nanogels were concentration-dependent. Furthermore, the florfenicol composite nanogels displayed good therapeutic efficacy against SCVs mastitis. Biological safety studies showed that the florfenicol composite nanogels might be a biocompatible preparation because of their non-toxic effects on the renal tissue and liver. Conclusions Florfenicol composite nanogels might improve the treatment of SCV infections.

Antibacterial activity of florfenicol composite nanogels against Staphylococcus aureus small colony variants

Introduction Biofilm formation is the major pathogenicity of Staphylococcus epidermidis (S. epidermidis), which enhances bacterial resistance to antibiotics. Isookanin has potential inhibitory activity on biofilm. Method The inhibiting mechanisms of isookanin against biofilm formation through surface hydrophobicity assay, exopolysaccharides, eDNA, gene expression analysis, microscopic visualization, and molecular docking were explored. Additionally, the combination of isookanin and β-lactam antibiotics were evaluated by the broth micro-checkerboard assay. Results The results showed that isookanin could decrease the biofilm formation of S. epidermidis by ≥85% at 250 μg/mL. The exopolysaccharides, eDNA and surface hydrophobicity were reduced after treatment with isookanin. Microscopic visualization analysis showed that there were fewer bacteria on the surface of the microscopic coverslip and the bacterial cell membrane was damaged after treatment with isookanin. The down-regulation of icaB and up-regulation of icaR were observed after treatment with isookanin. Additionally, the RNAIII gene was significantly up-regulated (p < 0.0001) at the mRNA level. Molecular docking showed that isookanin could bind to biofilm-related proteins. This indicated that isookanin can affect biofilm formation at the initial attachment phase and the aggregation phase. The FICI index showed that the combination of isookanin and β-lactam antibiotics were synergistic and could reduce doses of antibiotics by inhibiting biofilm formation. Discussion This study improved the antibiotic susceptibility of S. epidermidis through inhibition of the biofilm formation, and provided a guidance for the treatment of antibiotic resistance caused by biofilm

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Down-regulation of β-lactam antibiotics resistance and biofilm formation by Staphylococcus epidermidis is associated with isookanin

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Enhanced antibacterial activity of tilmicosin against Staphylococcus aureus small colony variants by chitosan oligosaccharide-sodium carboxymethyl cellulose composite nanogels

Jinhuan Liu

Papers

Enhanced antibacterial activity of tilmicosin against Staphylococcus aureus small colony variants by chitosan oligosaccharide-sodium carboxymethyl cellulose composite nanogels