title: Diversity, Antimicrobial Action and Structure-Activity Relationship of Buffalo Cathelicidins.
abstract: Cathelicidins are an ancient class of antimicrobial peptides (AMPs) with broad spectrum bactericidal activities. In this study, we investigated the diversity and biological activity of cathelicidins of buffalo, a species known for its disease resistance. A series of new homologs of cathelicidin4 (CATHL4), which were structurally diverse in their antimicrobial domain, was identified in buffalo. AMPs of newly identified buffalo CATHL4s (buCATHL4s) displayed potent antimicrobial activity against selected Gram positive (G+) and Gram negative (G-) bacteria. These peptides were prompt to disrupt the membrane integrity of bacteria and induced specific changes such as blebing, budding, and pore like structure formation on bacterial membrane. The peptides assumed different secondary structure conformations in aqueous and membrane-mimicking environments. Simulation studies suggested that the amphipathic design of buCATHL4 was crucial for water permeation following membrane disruption. A great diversity, broad-spectrum antimicrobial action, and ability to induce an inflammatory response indicated the pleiotropic role of cathelicidins in innate immunity of buffalo. This study suggests short buffalo cathelicidin peptides with potent bactericidal properties and low cytotoxicity have potential translational applications for the development of novel antibiotics and antimicrobial peptidomimetics.
authors.affiliation: Animal Genomics Lab, Animal Biotechnology Center, National Dairy Research Institute, Karnal, 132001, Haryana, India.
authors.forename: Biswajit
authors.initials: B
authors.lastname: Brahma
authors.affiliation: Animal Genomics Lab, Animal Biotechnology Center, National Dairy Research Institute, Karnal, 132001, Haryana, India.
authors.forename: Mahesh Chandra
authors.initials: MC
authors.lastname: Patra
authors.affiliation: Animal Genomics Lab, Animal Biotechnology Center, National Dairy Research Institute, Karnal, 132001, Haryana, India.
authors.forename: Satyanagalakshmi
authors.initials: S
authors.lastname: Karri
authors.affiliation: Animal Genomics Lab, Animal Biotechnology Center, National Dairy Research Institute, Karnal, 132001, Haryana, India.
authors.forename: Meenu
authors.initials: M
authors.lastname: Chopra
authors.affiliation: Animal Genomics Lab, Animal Biotechnology Center, National Dairy Research Institute, Karnal, 132001, Haryana, India.
authors.forename: Purusottam
authors.initials: P
authors.lastname: Mishra
authors.affiliation: Animal Genomics Lab, Animal Biotechnology Center, National Dairy Research Institute, Karnal, 132001, Haryana, India.
authors.forename: Bidhan Chandra
authors.initials: BC
authors.lastname: De
authors.affiliation: Animal Genomics Lab, Animal Biotechnology Center, National Dairy Research Institute, Karnal, 132001, Haryana, India.
authors.forename: Sushil
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Animal Genomics Lab, Animal Biotechnology Center, National Dairy Research Institute, Karnal, 132001, Haryana, India.
authors.forename: Sourav
authors.initials: S
authors.lastname: Mahanty
authors.affiliation: Animal Genomics Lab, Animal Biotechnology Center, National Dairy Research Institute, Karnal, 132001, Haryana, India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Thakur
authors.affiliation: Department of Biotechnology, Indian Institute of Technology, Roorkee, Uttarakhand, India.
authors.forename: Krishna Mohan
authors.initials: KM
authors.lastname: Poluri
authors.affiliation: Animal Genomics Lab, Animal Biotechnology Center, National Dairy Research Institute, Karnal, 132001, Haryana, India.
authors.forename: Tirtha Kumar
authors.initials: TK
authors.lastname: Datta
authors.affiliation: Animal Genomics Lab, Animal Biotechnology Center, National Dairy Research Institute, Karnal, 132001, Haryana, India.
authors.forename: Sachinandan
authors.initials: S
authors.lastname: De
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002020:Buffaloes; D054804:Cathelicidins / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002463:Cell Membrane Permeability / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D018628:Gene Dosage; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D011487:Protein Conformation; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D016207:Cytokines; D018836:Inflammation Mediators