Inhibition of biofilm and biofilm-associated virulence factor production in methicillin-resistant Staphylococcus aureus by docosanol

• Published in: Journal of biotechnology 2020-06, Vol.317, p.59-69
• Main Authors: Lakshmi, Selvaraj Alagu, Bhaskar, James Prabhanand, Krishnan, Venkateswaran, Sethupathy, Sivasamy, Pandipriya, Selvapandi, Aruni, Wilson, Pandian, Shunmugiah Karutha
• Format: Article
• Language: English
• Subjects: agr two-component system; Animals; Anti-Bacterial Agents - pharmacology; Anti-virulence; Antibiofilm; Biofilms - drug effects; Erythrocytes; Fatty Alcohols - pharmacology; Hemolysis - drug effects; Hemotoxins; Humans; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - metabolism; Sheep; Slime; Transcriptome - drug effects; Virulence Factors - metabolism
• ISSN: 0168-1656; 1873-4863
• DOI: 10.1016/j.jbiotec.2020.04.014

[Display omitted] •Docosanol, a potent antibiofilm agent against MRSA, characterized from Secondary metabolites of Streptomyces griseus.•Exhibits antivirulence properties against the foremost virulence factors responsible for brutal infections.•Reduces the survival rate of MRSA in human blood by augmenting the neurtrophil-mediated killing.•Down-regulates surface adhesion genes and virulence markers. Antimicrobial resistance is a major public health concern in infection control. Hence, a multi-pronged approach is necessary to curb the severity of infections. The present study entails the identification of docosanol (fatty alcohol) from Streptomyces as a novel antibiofilm agent which can target the virulence factors of MRSA. Results showed that docosanol as a potent antibiofilm agent and found to inhibit several virulence factors of MRSA. The antibiofilm efficacy of docosanol analyzed through light and scanning electron microscopy showed a significant reduction in adherent cells. Moreover, analysis of three-dimensional structure of biofilm matrix by confocal laser scanning microscope demonstrated effective antibiofilm potential of docosanol. In addition, docosanol reduced the survival rate of MRSA in healthy human blood and enhanced the neutrophil-mediated killing by interfering with hemolysin production. RT-qPCR analysis revealed the down regulation of several virulence genes, possibly by affecting the expression of the accessory gene regulator (agr) system and transcriptional regulator sarA. These findings suggest that docosanol could effectively reduce the biofilm phenotype and virulence production, and thus becomes a promising candidate to treat MRSA infections.