SD-8, a novel therapeutic agent active against multidrug-resistant Gram positive cocci

Biswajit Mishra, Vipul Kumar Srivastava, Rama Chaudhry, Rishi Kumar Somvanshi, Abhay Kumar Singh, Kamaldeep Gill, Ramesh Somvanshi, Ishan Kumar Patro, Sharmistha Dey

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Anti-bacterial drug resistance is one of the most critical concerns among the scientist worldwide. The novel antimicrobial decapeptide SD-8 is designed and its minimal inhibitory concentration and therapeutic index (TI) was found in the range of 1-8 μg/ml and 45-360, respectively, against major group of Gram positive pathogens (GPP). The peptide was also found to be least hemolytic at a concentration of 180 μg/ml, i.e., nearly 77 times higher than its average effective concentration. The kinetics assay showed that the killing time is 120 min for methicillin-sensitive Staphylococcus aureus (MSSA) and 90 min for methicillin-resistant S. aureus (MRSA). Membrane permeabilization is the cause of peptide antimicrobial activity as shown by the transmission electron microscopy studies. The peptide showed the anti-inflammatory property by inhibiting COX-2 with a K D and K i values of 2.36 × 10-9 and 4.8 × 10-8 M, respectively. The peptide was also found to be effective in vivo as derived from histopathological observations in a Staphylococcal skin infection rat model with MRSA as causative organism.

Original languageEnglish
Pages (from-to)1493-1505
Number of pages13
JournalAmino Acids
Volume39
Issue number5
DOIs
StatePublished - Nov 2010

Keywords

  • Anti-inflammatory
  • Antimicrobial peptides
  • Cyclooxygenase
  • Histopathology
  • Multidrug resistant
  • Surface plasmon resonance

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