A novel nitro-dexamethasone inhibits agr system activity and improves therapeutic effects in MRSA sepsis models without antibiotics

Scientific Reports
Yun YangHao Zeng

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) sepsis is a life-threatening medical condition that involves systemic inflammation throughout the body. Glucocorticoids are widely used in combination with antibiotics in the treatment of MRSA sepsis to fight the overwhelming inflammation. Here, we describe the improved anti-inflammatory properties of a nitric oxide (NO)-releasing derivative of dexamethasone, ND8008. ND8008 affected MRSA biofilm formation, caused biofilm cell death, and reduced the effects of virulence factors, such as α-toxin, by inhibiting the activity of the Staphylococcus aureus accessory gene regulator (agr) system. Dosing of mice with ND8008 (127.4 nmol/kg, i.p.) alone greatly reduced the inflammatory response caused by MRSA blood stream infection and considerably increased the survival rate of septic mice. These findings suggest that this novel NO-releasing derivative of dexamethasone ND8008 could be helpful in the treatment of MRSA sepsis.

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Citations

Dec 27, 2016·Frontiers in Immunology·Karolina A ZielińskaPhilippe E Van den Steen
Dec 6, 2017·Scientific Reports·Yang ZhangQing-Zhen Han
Feb 3, 2021·Infection and Immunity·Sarah E RoweBrian P Conlon
Aug 23, 2019·Organic Letters·Samuel ThurowIgor D Jurberg

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Methods Mentioned

BETA
scanning electron microscopy
light microscopy
ELISA
PCR

Software Mentioned

Graphpad Prism

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