title: Ancient antimicrobial peptides kill antibiotic-resistant pathogens: Australian mammals provide new options.
abstract: BACKGROUND
  To overcome the increasing resistance of pathogens to existing antibiotics the 10×'20 Initiative declared the urgent need for a global commitment to develop 10 new antimicrobial drugs by the year 2020. Naturally occurring animal antibiotics are an obvious place to start. The recently sequenced genomes of mammals that are divergent from human and mouse, including the tammar wallaby and the platypus, provide an opportunity to discover novel antimicrobials. Marsupials and monotremes are ideal potential sources of new antimicrobials because they give birth to underdeveloped immunologically naïve young that develop outside the sterile confines of a uterus in harsh pathogen-laden environments. While their adaptive immune system develops innate immune factors produced either by the mother or by the young must play a key role in protecting the immune-compromised young. In this study we focus on the cathelicidins, a key family of antimicrobial peptide genes.
  
  
  RESULTS
  We identified 14 cathelicidin genes in the tammar wallaby genome and 8 in the platypus genome. The tammar genes were expressed in the mammary gland during early lactation before the adaptive immune system of the young develops, as well as in the skin of the pouch young. Both platypus and tammar peptides were effective in killing a broad range of bacterial pathogens. One potent peptide, expressed in the early stages of tammar lactation, effectively killed multidrug-resistant clinical isolates of Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii.
  
  
  CONCLUSIONS
  Marsupial and monotreme young are protected by antimicrobial peptides that are potent, broad spectrum and salt resistant. The genomes of our distant relatives may hold the key for the development of novel drugs to combat multidrug-resistant pathogens.
authors.affiliation: Biosciences Research Division, Department of Primary Industries, Bundoora, Australia.
authors.forename: Jianghui
authors.initials: J
authors.lastname: Wang
authors.forename: Emily S W
authors.initials: ES
authors.lastname: Wong
authors.forename: Jane C
authors.initials: JC
authors.lastname: Whitley
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Stringer
authors.forename: Kirsty R
authors.initials: KR
authors.lastname: Short
authors.forename: Marilyn B
authors.initials: MB
authors.lastname: Renfree
authors.forename: Katherine
authors.initials: K
authors.lastname: Belov
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Cocks
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology* / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects; D002417:Cattle; D057225:Data Mining; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D007614:Macropodidae / Q000235:genetics*; D051379:Mice; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010802:Phylogeny; D010987:Platypus / Q000235:genetics*; D012988:Soil Microbiology; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins