PMID- 28089718
OWN - NLM
STAT- MEDLINE
DCOM- 20171116
LR  - 20221207
IS  - 1879-0089 (Electronic)
IS  - 0145-305X (Linking)
VI  - 70
DP  - 2017 May
TI  - Cathelicidin antimicrobial peptide from Alligator mississippiensis has 
      antibacterial activity against multi-drug resistant Acinetobacter baumanii and 
      Klebsiella pneumoniae.
PG  - 135-144
LID - S0145-305X(16)30429-3 [pii]
LID - 10.1016/j.dci.2017.01.011 [doi]
AB  - Alligator mississippiensis (American alligator), a member of order Crocodilia, 
      lives in bacteria-laden environments but is not often known to succumb to 
      bacterial infections. Their serum has been shown to have antibacterial activity 
      beyond that of human serum, and it is believed that this activity is partially 
      due to cationic antimicrobial peptides (CAMPs). CAMPs are produced by many 
      organisms as part of the innate immune system. CAMPs are attractive possible 
      therapies against multi-drug resistant bacteria, such as those found in 
      biofilm-infected war wounds, because they seldom cause genetic resistance in 
      bacteria and are effective against antibiotic resistant bacteria. In this work, 
      we identified, synthesized, and characterized a cathelicidin and two shorter 
      fragments from the American alligator. We discovered the cathelicidin using Basic 
      Local Alignment Search Tool (BLAST) alignment and by comparing 
      A. mississippiensis expressed sequence tags (ESTs) with propeptide cathelicidins 
      of other reptiles. We analyzed the structure using bioinformatics tools and 
      circular dichroism and predicted that the full-length cathelicidin peptide has a 
      mixed structure, with an N-terminal alpha-helix and a center Pro hinge. In minimal 
      inhibitory concentration (MIC) assays, it was determined that the cathelicidin 
      and the two shorter fragments have strong activity against multiple Gram-negative 
      bacteria, including clinical isolates of multi-drug resistant (MDR) Acinetobacter 
      baumannii and carbapenem-resistant Klebsiella pneumoniae. Using the ethidium 
      bromide uptake assay, it was found that these peptides permeabilize the bacterial 
      membrane and are less sensitive to salt inhibition than many other known CAMPs. 
      The alligator cathelicidin peptides were not hemolytic against sheep red blood 
      cells at 300 mug/ml and were not significantly cytotoxic against A549 human lung 
      epithelial cells after 24 h exposure in 
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. These 
      alligator cathelicidin peptides have activity similar to other CAMPs from 
      reptiles such as NA-CATH. It is possible that the alligator cathelicidins play an 
      important role in the innate immune response of A. mississippiensis, similar to 
      LL-37 in humans. In addition, due to their activities against MDR bacteria and 
      lack of cytotoxicity, the AM-CATH peptides could be an attractive platform for 
      further development as a potential therapeutic.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Barksdale, Stephanie M
AU  - Barksdale SM
AD  - School of Systems Biology, George Mason University, Manassas, VA, USA.
FAU - Hrifko, Evelyn J
AU  - Hrifko EJ
AD  - College of Science, George Mason University, Manassas, VA, USA.
FAU - van Hoek, Monique L
AU  - van Hoek ML
AD  - School of Systems Biology, George Mason University, Manassas, VA, USA; College of 
      Science, George Mason University, Manassas, VA, USA; National Center for 
      Biodefense and Infectious Diseases, George Mason University, Manassas, VA, USA. 
      Electronic address: mvanhoek@gmu.edu.
LA  - eng
PT  - Journal Article
DEP - 20170113
PL  - United States
TA  - Dev Comp Immunol
JT  - Developmental and comparative immunology
JID - 7708205
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Antimicrobial Cationic Peptides)
RN  - 0 (Arthropod Proteins)
RN  - 0 (Hemolytic Agents)
RN  - 0 (antilipopolysaccharide factor (Limulus))
RN  - 0 (Cathelicidins)
SB  - IM
MH  - Acinetobacter Infections/complications/*immunology
MH  - Acinetobacter baumannii/*immunology
MH  - Alligators and Crocodiles/*immunology
MH  - Animals
MH  - Anti-Bacterial Agents/*immunology
MH  - Antimicrobial Cationic Peptides/*immunology
MH  - Arthropod Proteins/*immunology
MH  - Biofilms/*growth & development
MH  - Cell Survival
MH  - Computational Biology
MH  - Drug Resistance, Microbial
MH  - Hemolytic Agents/*metabolism
MH  - Immunity, Innate
MH  - Klebsiella Infections/complications/*immunology
MH  - Klebsiella pneumoniae/*immunology
MH  - Phylogeny
MH  - Sequence Alignment
MH  - Cathelicidins
EDAT- 2017/01/17 06:00
MHDA- 2017/11/29 06:00
CRDT- 2017/01/17 06:00
PHST- 2016/11/18 00:00 [received]
PHST- 2017/01/10 00:00 [revised]
PHST- 2017/01/10 00:00 [accepted]
PHST- 2017/01/17 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2017/01/17 06:00 [entrez]
AID - S0145-305X(16)30429-3 [pii]
AID - 10.1016/j.dci.2017.01.011 [doi]
PST - ppublish
SO  - Dev Comp Immunol. 2017 May;70:135-144. doi: 10.1016/j.dci.2017.01.011. Epub 2017 
      Jan 13.