title: Highly potent antimicrobial peptides from N-terminal membrane-binding region of E. coli MreB.
abstract: Microbial pathogenesis is a serious health concern. The threat escalates as the existing conventional antimicrobials are losing their efficacy against the evolving pathogens. Peptides hold promise to be developed into next-generation antibiotics. Antimicrobial peptides adopt amphipathic structures that could selectively bind to and disrupt the microbial membranes. Interaction of proteins with membranes is central to all living systems and we reasoned that the membrane-binding domains in microbial proteins could be developed into efficient antimicrobials. This is an interesting approach as self-like sequences could elude the microbial strategies of degrading the antimicrobial peptides, one of the mechanisms of showing resistance to antimicrobials. We selected the 9-residue-long membrane-binding region of E. coli MreB protein. The 9-residue peptide (C-terminal amide) and its N-terminal acetylated analog displayed broad-spectrum activity, killing Gram-negative bacteria, Gram-positive bacteria, and fungi. Extension with a tryptophan residue at the N-terminus drastically improved the activity of the peptides with lethal concentrations ≤10 μM against all the organisms tested. The tryptophan-extended peptides caused complete killing of C. albicans as well as gentamicin and methicillin resistant S. aureus at 5 μM concentration. Lipid-binding studies and electron microscopic analyses of the peptide-treated microbes suggest membrane disruption as the mechanism of killing.
authors.affiliation: Department of Biosciences and Bioengineering Indian Institute of Technology Guwahati, Guwahati - 781 039, India.
authors.forename: Karabi
authors.initials: K
authors.lastname: Saikia
authors.affiliation: Department of Biosciences and Bioengineering Indian Institute of Technology Guwahati, Guwahati - 781 039, India.
authors.forename: Yalavarthi Durga
authors.initials: YD
authors.lastname: Sravani
authors.affiliation: Department of Biosciences and Bioengineering Indian Institute of Technology Guwahati, Guwahati - 781 039, India.
authors.forename: Vibin
authors.initials: V
authors.lastname: Ramakrishnan
authors.affiliation: Department of Biosciences and Bioengineering Indian Institute of Technology Guwahati, Guwahati - 781 039, India.
authors.forename: Nitin
authors.initials: N
authors.lastname: Chaudhary
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D000072417:Protein Domains; D012965:Sodium Chloride / Q000737:chemistry; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D029968:Escherichia coli Proteins; C078473:MreB protein, E coli; D012965:Sodium Chloride; D014364:Tryptophan