Synthesis, antimicrobial activity and conformational analysis of the class IIa bacteriocin pediocin PA-1 and analogs thereof

The antimicrobial peptide pediocin PA-1 is a class IIa bacteriocin that inhibits several clinically relevant pathogens including Listeria spp. Here we report the synthesis and characterization of whole pediocin PA-1 and novel analogs thereof using a combination of solid- and solution-phase strategie...

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Bibliographic Details
Published in:Scientific reports 2018-06, Vol.8 (1), p.9029-13, Article 9029
Main Authors: Bédard, François, Hammami, Riadh, Zirah, Séverine, Rebuffat, Sylvie, Fliss, Ismail, Biron, Eric
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Anti-Infective Agents - chemical synthesis
Anti-Infective Agents - chemistry
Anti-Infective Agents - pharmacology
Antimicrobial activity
Antimicrobial agents
Bacteriocins - chemistry
Bacteriocins - pharmacology
Chemical Sciences
Circular dichroism
Clostridium perfringens - drug effects
Conformational analysis
Listeria
Listeria monocytogenes
Listeria monocytogenes - drug effects
Magnetic Resonance Spectroscopy
Medicinal Chemistry
Microbial Sensitivity Tests - methods
Minimum inhibitory concentration
Models, Chemical
Models, Molecular
NMR
Nuclear magnetic resonance
Pathogens
Pediocin
Pediocins - chemical synthesis
Pediocins - chemistry
Pediocins - pharmacology
Protein Conformation
Structure-Activity Relationship
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Summary:The antimicrobial peptide pediocin PA-1 is a class IIa bacteriocin that inhibits several clinically relevant pathogens including Listeria spp. Here we report the synthesis and characterization of whole pediocin PA-1 and novel analogs thereof using a combination of solid- and solution-phase strategies to overcome difficulties due to instability and undesired reactions. Pediocin PA-1 thus synthesized was a potent inhibitor of Listeria monocytogenes (MIC = 6.8 nM), similar to the bacteriocin produced naturally by Pediococcus acidilactici. Of particular interest is that linear analogs lacking both of the disulfide bridges characterizing pediocin PA-1 were as potent. One linear analog was also a strong inhibitor of Clostridium perfringens, another important food-borne pathogen. These results are discussed in light of conformational information derived from circular dichroism, solution NMR spectroscopy and structure-activity relationship studies.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-27225-3