TY - JOUR
T1 - Intracellular Bacterial Targeting by a Thiazolyl Benzenesulfonamide and Octaarginine Peptide Complex
AU - Ratrey, Poonam
AU - Datta, Bhaskar
AU - Mishra, Abhijit
N1 - Publisher Copyright:
© 2022 The Authors. Published by American Chemical Society.
PY - 2022/7/18
Y1 - 2022/7/18
N2 - A brominated thiazolyl benzenesulfonamide (BTB) derivative is conjugated with the cell-penetrating peptide octaarginine (R8) in an effort to construct innovative antibacterial products. The noncovalent complex of BTB and R8 is characterized by Fourier transform infrared (FTIR) spectroscopy, which indicates hydrogen bonding between the two constituents. Attachment of the peptide moiety renders aqueous solubility to the hydrophobic benzenesulfonamide drug and bestows bactericidal activity. Confocal imaging in conjunction with dye probes shows successful clearance of intracellular Staphylococcus aureus bacteria by the BTB-R8 complex. Scanning electron micrographs and studies with a set of fluorescent dyes suggest active disruption of the bacterial cell membrane by the BTB-R8 complex. In contrast, the complex of BTB with octalysine (K8) fails to cause membrane damage and displays a modest antibacterial effect. A complex of BTB with the water-soluble hydrophilic polymer poly(vinylpyrrolidone) (PVP) does not display any antibacterial effect, indicating the distinctive role of the cell-penetrating peptide (CPP) R8 in the cognate complex. The leakage of the encapsulated dye from giant unilamellar vesicles upon interaction with the BTB-R8 complex further highlights the membrane activity of the complex, which cannot be accomplished by bare sulfonamide alone. This work broadens the scope of use of CPPs with respect to eliciting antibacterial activity and potentially expands the limited arsenal of membrane-targeting antibiotics.
AB - A brominated thiazolyl benzenesulfonamide (BTB) derivative is conjugated with the cell-penetrating peptide octaarginine (R8) in an effort to construct innovative antibacterial products. The noncovalent complex of BTB and R8 is characterized by Fourier transform infrared (FTIR) spectroscopy, which indicates hydrogen bonding between the two constituents. Attachment of the peptide moiety renders aqueous solubility to the hydrophobic benzenesulfonamide drug and bestows bactericidal activity. Confocal imaging in conjunction with dye probes shows successful clearance of intracellular Staphylococcus aureus bacteria by the BTB-R8 complex. Scanning electron micrographs and studies with a set of fluorescent dyes suggest active disruption of the bacterial cell membrane by the BTB-R8 complex. In contrast, the complex of BTB with octalysine (K8) fails to cause membrane damage and displays a modest antibacterial effect. A complex of BTB with the water-soluble hydrophilic polymer poly(vinylpyrrolidone) (PVP) does not display any antibacterial effect, indicating the distinctive role of the cell-penetrating peptide (CPP) R8 in the cognate complex. The leakage of the encapsulated dye from giant unilamellar vesicles upon interaction with the BTB-R8 complex further highlights the membrane activity of the complex, which cannot be accomplished by bare sulfonamide alone. This work broadens the scope of use of CPPs with respect to eliciting antibacterial activity and potentially expands the limited arsenal of membrane-targeting antibiotics.
KW - Bactericidal
KW - Cell-penetrating peptide
KW - Giant unilamellar vesicles
KW - Membrane-active
KW - Octaarginine
KW - Thiazolyl benzenesulfonamide
UR - http://www.scopus.com/inward/record.url?scp=85134539007&partnerID=8YFLogxK
U2 - 10.1021/acsabm.2c00252
DO - 10.1021/acsabm.2c00252
M3 - Article
C2 - 35736131
AN - SCOPUS:85134539007
SN - 2576-6422
VL - 5
SP - 3257
EP - 3268
JO - ACS Applied Bio Materials
JF - ACS Applied Bio Materials
IS - 7
ER -