R-Thanatin Inhibits Growth and Biofilm Formation of Methicillin-Resistant Staphylococcus epidermidis In Vivo and In Vitro

Abstract

cStaphylococcus epidermidis is one of the most frequent causes of device-associated infections, because it is known to cause biofilms that grow on catheters or other surgical implants. The persistent increasing resistance of S. epidermidis and other coagulase-negative staphylococci (CoNS) has driven the need for newer antibacterial agents with innovative therapeutic strategies. Thanatin is reported to display potent antibiotic activities, especially against extended-spectrum-beta-lactamase-producing Escherichia coli. The present study aimed to investigate whether a shorter derivative peptide (R-thanatin) could be used as a novel antibacterial agent. We found that R-thanatin was highly potent in vitro against coagulase-negative staphylococci, such as S. epidermidis, S. haemolyticus, and S. hominis, and inhibited biofilm formation at subinhibitory concentrations. Properties of little toxicity to human red blood cells (hRBCs) and human umbilical vein endothelial cells, a low incidence of resistance, and relatively high stability in plasma were confirmed. Excellent in vivo protective effects were also observed using a methicillinresistant S. epidermidis (MRSE)-induced urinary tract infection rat model. Electron microscopy and confocal laser-scanning microscopy analyses suggested that R-thanatin disturbed cell division of MRSE severely, which might be the reason for inhibition of MRSE growth. These findings indicate that R-thanatin is active against the growth and biofilm formation of MRSE in vitro and in vivo. R-thanatin might be considered as a specific drug candidate for treating CoNS infections.

Selective in vivo and in vitro activities of 3,3′-4-nitrobenzylidene-bis-4-hydroxycoumarin against methicillin-resistant Staphylococcus aureus by inhibition of DNA polymerase III

“…Cytotoxicity of NBH to TR146 cells, which originated from a human neck metastasis of buccal carcinoma, was determined through standard MTT assay according to a previously established method2930. TR146 cells were seeded in 96-well microtitre plate at a density of 1 × 10 4 cells/well.…”

Thanatin confers partial resistance against aflatoxigenic fungi in maize (Zea mays)

“…Thanatin has little hemolytic effect against eukaryotic cells, but the truncated derivative R-thanatin (12 amino acids) and the substituted derivative thanatin(S) are promising candidates to address the emergence of methicillin-resistant Staphylococcus spp. and Klebsiella pneumonia (Hou et al 2013;Wu et al 2011Wu et al , 2012. These examples demonstrate the versatility of thanatin and its derivatives to combat microbial diseases in both plants and humans.…”

Antimicrobial peptides of invertebrates. Part 1. structure, biosynthesis, and evolution

“…In addition, thanatin and androctonin initially exhibit low hemolytic activity that can be decreased for other representatives of this group by amino acid substitu tions [134]. Thanatin and its derivatives have been shown to inhibit growth of pathogenic strains with multiple medicinal resistance, including those in the in vivo models and in biofilms [135][136][137][138]. A spectrum of the activity of the β pin AMPs is not limited by microorganisms.…”