Chicken cathelicidins as potent intrinsically disordered biocides with antimicrobial activity against infectious pathogens.
This study was performed to identify the expression patterns of the cathelicidin genes in a local chicken breed and to evaluate the antimicrobial activities of the cathelicidin peptides against pathogenic bacteria. This analysis revealed that the coding regions of CATH-1, -2, and -3 genes contain 447 bp, 465 bp, and 456 bp, respectively, and encode proteins of 148, 154, 151 amino acids, respectively. The complete amino acid sequences of the cathelicidin peptides are similar to those found in Meleagris gallopavo, Phasianus colchicus, and Coturnix coturnix, and show high sequence identity to their Columba livia and Anas platyrhynchos counterparts. In contrast, these avian peptides shared a very low sequence identity with the mammalian cathelicidins. The analysis further revealed that the cathelicidin genes are expressed in various organ and tissues. We also show that the CATH peptides 1, 2, 3 and their amide-modified structures possess potent antimicrobial activities against both Gram-positive and Gram-negative pathogens, with these bacteria being affected to different extents. The antimicrobial activities of the peptides are slightly lower than those of their amide analogs. Computational analysis revealed that pre-pro-cathelicidins are hybrid proteins that contain ordered domains and functional intrinsically disordered regions. Furthermore, high structural and sequence variability of mature cathelicidins is a strong indication of their rather disordered nature. It is likely that intrinsic disorder is needed for the multifarious functionality of these antimicrobial peptides. Our analyses indicated that cathelicidin peptides require further study to better understand their full potentials in the treatment of diseases in both humans and animals. The data obtained for synthetic avian peptides will help elucidating of their potential applications in the pharmaceutical industry.
Biological Sciences Department, Faculty of Science, University of Jeddah, P.O. Box 80203, Jeddah, Saudi Arabia; Cell Biology Department, Genetic Engineering and Biotechnology Division, National Research Centre, Dokki, P.O. Box 12622, Gizza, Egypt. Electronic address: haithamyacoub46@gmail.com.
Haitham A
HA
Yacoub
Biological Sciences Department, Faculty of Science, University of Jeddah, P.O. Box 80203, Jeddah, Saudi Arabia; Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, P.O. Box 12622, Gizza, Egypt. Electronic address: ahmedazazy8@hotmail.com.
Ahmed M
AM
Elazzazy
King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia; Department of Molecular Genetics and Enzymology, Davison of Human Genetics and Genome Research, National Research Centre, Dokki, P.O. Box 12622, Gizza, Egypt.
Maged M
MM
Mahmoud
Biological Sciences Department, Faculty of Science, University of Jeddah, P.O. Box 80203, Jeddah, Saudi Arabia; Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah, Saudi Arabia.
Mohamed Nabih
MN
Baeshen
Biological Sciences Department, Faculty of Science, University of Jeddah, P.O. Box 80203, Jeddah, Saudi Arabia.
Omar A
OA
Al-Maghrabi
Embryonic Stem Cell Unit, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia; Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah, Saudi Arabia.
Saleh
S
Alkarim
Cell Biology Department, Genetic Engineering and Biotechnology Division, National Research Centre, Dokki, P.O. Box 12622, Gizza, Egypt.
Ekram S
ES
Ahmed
Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah, Saudi Arabia.
Hussein A
HA
Almehdar
Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah, Saudi Arabia; Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia; Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA. Electronic address: vuversky@health.usf.edu.
Vladimir N
VN
Uversky
D000577:Amides / Q000737:chemistry; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism*; D044822:Biodiversity; D054804:Cathelicidins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002645:Chickens / Q000276:immunology*; D019295:Computational Biology; D004202:Disinfectants / Q000737:chemistry / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D008322:Mammals; D010802:Phylogeny; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D059467:Transcriptome
D000577:Amides; D000890:Anti-Infective Agents; D054804:Cathelicidins; D004202:Disinfectants
Antimicrobial activity; Bacteria; Cathelicidin genes; Intrinsically disordered proteins; Natural antibiotic; Transcription profile