title: Antimicrobial and antibiofilm activity of LL-37 and its truncated variants against Burkholderia pseudomallei.
abstract: The Gram-negative bacterium Burkholderia pseudomallei is the aetiological agent of melioidosis, which is an endemic disease in tropical areas of Southeast Asia and Northern Australia. Burkholderia pseudomallei has intrinsic resistance to a number of commonly used antibiotics and has also been reported to develop a biofilm. Resistance to killing by antimicrobial agents is one of the hallmarks of bacteria grown in biofilm. The aim of this study was to determine the antimicrobial activity and mechanisms of action of LL-37 and its truncated variants against B. pseudomallei both in planktonic and biofilm form, as LL-37 is an antimicrobial peptide that possessed strong killing activity against several pathogens. Antimicrobial assays revealed that LL-31, a truncated variant of LL-37 lacking the six C-terminus residues, exhibited the strongest killing effect. Time-kill experiments showed that 20 μM LL-31 can reach the bactericidal endpoint within 2h. Freeze-fracture electron microscopy of bacterial cells demonstrated that these peptides disrupt the membrane and cause leakage of intracellular molecules leading to cell death. Moreover, LL-31 also possessed stronger bactericidal activity than ceftazidime against B. pseudomallei grown in biofilm. Thus, LL-31 should be considered as a potent antimicrobial agent against B. pseudomallei both in planktonic and biofilm form.
authors: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors: Sakawrat
authors: S
authors: Kanthawong
authors: Jan G M
authors: JG
authors: Bolscher
authors: Enno C I
authors: EC
authors: Veerman
authors: Jan
authors: J
authors: van Marle
authors: Hans J J
authors: HJ
authors: de Soet
authors: Kamran
authors: K
authors: Nazmi
authors: Surasakdi
authors: S
authors: Wongratanacheewin
authors: Suwimol
authors: S
authors: Taweechaisupapong
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D001210:Asia, Southeastern; D001315:Australia; D018441:Biofilms / Q000187:drug effects*; D016957:Burkholderia pseudomallei / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D005614:Freeze Fracturing; D006801:Humans; D008554:Melioidosis / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D054804:Cathelicidins
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D050505:Mutant Proteins; D054804:Cathelicidins