Novel Antimicrobial Peptides in Alligator and Crocodile



Barksdale, Stephanie

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Novel antibiotics are needed to fight the rising tide of drug resistance in pathogenic bacteria. One possible source is cationic antimicrobial peptides (CAMPs), small proteins produced by the innate immune system. CAMPs have a range of mechanisms including direct antibacterial action and immunomodulatory effects. Crocodilians are part of an ancient clade, the Archosaurs, and are more closely related to birds and dinosaurs than other living reptiles. Very little is known about the innate immune systems of crocodilians, but research has found that the serum of these species have antimicrobial activity beyond that of human serum. This activity is thought to be partly due to CAMPs, though only a handful of crocodilian CAMPs have been described. In this thesis, four novel CAMPs from members of the order Crocodilia are investigated. A hepcidin from Crocodylus siamensis, an iron-regulating peptide with 4 intramolecular disulfide bonds, is found to have weak activity against Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus. Two fragments of an apolipoprotein found in the blood of Alligator mississippiensis were found to have strong activity against a range of Gram negative and Gram positive bacteria, including multi-drug resistant bacteria. These fragments were found to be alpha-helical and to depolarize the bacterial membrane. A cathelicidin from A. mississippiensis is strongly active against P. aeruginosa and multi-drug resistant Acinetobacter baumannii and permeabilizes the bacterial membrane. These analyses give us greater understanding of the crocodilian innate immune system. In addition, these CAMPs could be used as a basis for new antimicrobials.


This thesis has been embargoed for 1 year and will not be available until November 2016.


Crocodilians, Bacteria, Antimicrobial peptides, Innate immunity