PMID- 25785690
OWN - NLM
STAT- MEDLINE
DCOM- 20160204
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 3
DP  - 2015
TI  - Human beta-defensin 4 with non-native disulfide bridges exhibit antimicrobial 
      activity.
PG  - e0119525
LID - 10.1371/journal.pone.0119525 [doi]
LID - e0119525
AB  - Human defensins play multiple roles in innate immunity including direct 
      antimicrobial killing and immunomodulatory activity. They have three disulfide 
      bridges which contribute to the stability of three anti-parallel beta-strands. The 
      exact role of disulfide bridges and canonical beta-structure in the antimicrobial 
      action is not yet fully understood. In this study, we have explored the 
      antimicrobial activity of human beta-defensin 4 (HBD4) analogs that differ in the 
      number and connectivity of disulfide bridges. The cysteine framework was similar 
      to the disulfide bridges present in mu-conotoxins, an unrelated class of peptide 
      toxins. All the analogs possessed enhanced antimicrobial potency as compared to 
      native HBD4. Among the analogs, the single disulfide bridged peptide showed 
      maximum potency. However, there were no marked differences in the secondary 
      structure of the analogs. Subtle variations were observed in the localization and 
      membrane interaction of the analogs with bacteria and Candida albicans, 
      suggesting a role for disulfide bridges in modulating their antimicrobial action. 
      All analogs accumulated in the cytosol where they can bind to anionic molecules 
      such as nucleic acids which would affect several cellular processes leading to 
      cell death. Our study strongly suggests that native disulfide bridges or the 
      canonical beta-strands in defensins have not evolved for maximal activity but they 
      play important roles in determining their antimicrobial potency.
FAU - Sharma, Himanshu
AU  - Sharma H
AD  - CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India.
FAU - Nagaraj, Ramakrishnan
AU  - Nagaraj R
AD  - CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150318
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Conotoxins)
RN  - 0 (DEFB4A protein, human)
RN  - 0 (Disulfides)
RN  - 0 (Peptides)
RN  - 0 (beta-Defensins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Anti-Bacterial Agents/chemistry/*pharmacology
MH  - Candida albicans/drug effects/growth & development/ultrastructure
MH  - Conotoxins/chemistry
MH  - Cytosol/drug effects/metabolism
MH  - Disulfides/*chemistry
MH  - Escherichia coli/drug effects/growth & development/ultrastructure
MH  - Humans
MH  - Immunity, Innate
MH  - Microbial Sensitivity Tests
MH  - Microbial Viability/drug effects
MH  - Molecular Sequence Data
MH  - Peptides/chemical synthesis/chemistry/*pharmacology
MH  - Protein Structure, Secondary
MH  - Pseudomonas aeruginosa/drug effects/growth & development/ultrastructure
MH  - Solid-Phase Synthesis Techniques
MH  - Staphylococcus aureus/drug effects/growth & development/ultrastructure
MH  - beta-Defensins/chemistry/*pharmacology
PMC - PMC4364940
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/03/19 06:00
MHDA- 2016/02/05 06:00
PMCR- 2015/03/18
CRDT- 2015/03/19 06:00
PHST- 2014/10/02 00:00 [received]
PHST- 2015/01/14 00:00 [accepted]
PHST- 2015/03/19 06:00 [entrez]
PHST- 2015/03/19 06:00 [pubmed]
PHST- 2016/02/05 06:00 [medline]
PHST- 2015/03/18 00:00 [pmc-release]
AID - PONE-D-14-43946 [pii]
AID - 10.1371/journal.pone.0119525 [doi]
PST - epublish
SO  - PLoS One. 2015 Mar 18;10(3):e0119525. doi: 10.1371/journal.pone.0119525. 
      eCollection 2015.