TY - JOUR
T1 - SD-8, a novel therapeutic agent active against multidrug-resistant Gram positive cocci
AU - Mishra, Biswajit
AU - Srivastava, Vipul Kumar
AU - Chaudhry, Rama
AU - Somvanshi, Rishi Kumar
AU - Singh, Abhay Kumar
AU - Gill, Kamaldeep
AU - Somvanshi, Ramesh
AU - Patro, Ishan Kumar
AU - Dey, Sharmistha
N1 - Funding Information:
Authors acknowledge financial support from the Indian Council Medical Research, Department of Science and Technology, Council of Scientific and Industrial Research, Government of India and SAIF facility, All India Institute of Medical Sciences for performing TEM.
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
KW - Anti-inflammatory
KW - Antimicrobial peptides
KW - Cyclooxygenase
KW - Histopathology
KW - Multidrug resistant
KW - Surface plasmon resonance
UR - http://www.scopus.com/inward/record.url?scp=78449311798&partnerID=8YFLogxK
U2 - 10.1007/s00726-010-0618-z
DO - 10.1007/s00726-010-0618-z
M3 - Article
C2 - 20473534
AN - SCOPUS:78449311798
SN - 0939-4451
VL - 39
SP - 1493
EP - 1505
JO - Amino Acids
JF - Amino Acids
IS - 5
ER -