title: Effective control of Salmonella infections by employing combinations of recombinant antimicrobial human β-defensins hBD-1 and hBD-2.
abstract: We successfully produced two human β-defensins (hBD-1 and hBD-2) in bacteria as functional peptides and tested their antibacterial activities against Salmonella enterica serovar Typhi, Escherichia coli, and Staphylococcus aureus employing both spectroscopic and viable CFU count methods. Purified peptides showed approximately 50% inhibition of the bacterial population when used individually and up to 90% when used in combination. The 50% lethal doses (LD50) of hBD-1 against S. Typhi, E. coli, and S. aureus were 0.36, 0.40, and 0.69 μg/μl, respectively, while those for hBD-2 against the same bacteria were 0.38, 0.36, and 0.66 μg/μl, respectively. Moreover, we observed that bacterium-derived antimicrobial peptides were also effective in increasing survival time and decreasing bacterial loads in the peritoneal fluid, liver, and spleen of a mouse intraperitoneally infected with S. Typhi. The 1:1 hBD-1/hBD-2 combination showed maximum effectiveness in challenging the Salmonella infection in vitro and in vivo. We also observed less tissue damage and sepsis formation in the livers of infected mice after treatment with hBD-1 and hBD-2 peptides individually or in combination. Based on these findings, we conclude that bacterium-derived recombinant β-defensins (hBD-1 and hBD-2) are promising antimicrobial peptide (AMP)-based substances for the development of new therapeutics against typhoid fever.
authors.affiliation: Division of Gene Function and Regulation, Institute of Life Sciences, Department of Biotechnology, Government of India, Bhubaneswar, Odisha, India.
authors.forename: Soumitra
authors.initials: S
authors.lastname: Maiti
authors.affiliation: Division of Gene Function and Regulation, Institute of Life Sciences, Department of Biotechnology, Government of India, Bhubaneswar, Odisha, India.
authors.forename: Sunita
authors.initials: S
authors.lastname: Patro
authors.affiliation: Division of Gene Function and Regulation, Institute of Life Sciences, Department of Biotechnology, Government of India, Bhubaneswar, Odisha, India.
authors.forename: Sukumar
authors.initials: S
authors.lastname: Purohit
authors.affiliation: Division of Gene Function and Regulation, Institute of Life Sciences, Department of Biotechnology, Government of India, Bhubaneswar, Odisha, India.
authors.forename: Sumeet
authors.initials: S
authors.lastname: Jain
authors.affiliation: Division of Gene Function and Regulation, Institute of Life Sciences, Department of Biotechnology, Government of India, Bhubaneswar, Odisha, India.
authors.forename: Shantibhusan
authors.initials: S
authors.lastname: Senapati
authors.affiliation: Division of Gene Function and Regulation, Institute of Life Sciences, Department of Biotechnology, Government of India, Bhubaneswar, Odisha, India nrisinghad@yahoo.com.
authors.forename: Nrisingha
authors.initials: N
authors.lastname: Dey
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000627:therapeutic use; D003001:Cloning, Molecular; D004359:Drug Therapy, Combination; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D011994:Recombinant Proteins / Q000627:therapeutic use; D012480:Salmonella Infections / Q000188:drug therapy* / Q000382:microbiology; D012485:Salmonella typhi / Q000187:drug effects; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects; D023083:beta-Defensins / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C406407:DEFB1 protein, human; C106641:DEFB4A protein, human; D011994:Recombinant Proteins; D023083:beta-Defensins