SD-8, a novel therapeutic agent active against multidrug-resistant Gram positive cocci.
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 KD and Ki 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.
Mishra
Biswajit
B
Department of Biophysics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
Srivastava
Vipul Kumar
VK
Chaudhry
Rama
R
Somvanshi
Rishi Kumar
RK
Singh
Abhay Kumar
AK
Gill
Kamaldeep
K
Somvanshi
Ramesh
R
Patro
Ishan Kumar
IK
Dey
Sharmistha
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000097:blood / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D006095:Gram-Positive Cocci / Q000187:drug effects* / Q000254:growth & development; D006461:Hemolysis; D006801:Humans; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D012995:Solubility; D020349:Surface Plasmon Resonance
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D052246:Cyclooxygenase 2 Inhibitors; D010455:Peptides; C556023:SD-8 peptide; D051546:Cyclooxygenase 2