Plantaricin NC8 αβ exerts potent antimicrobial activity against Staphylococcus spp. and enhances the effects of antibiotics

Abstract

The use of conventional antibiotics has substantial clinical efficacy, however these vital antimicrobial agents are becoming less effective due to the dramatic increase in antibiotic-resistant bacteria. Novel approaches to combat bacterial infections are urgently needed and bacteriocins represent a promising alternative. In this study, the activities of the two-peptide bacteriocin PLNC8 αβ were investigated against different Staphylococcus spp. The peptide sequences of PLNC8 α and β were modified, either through truncation or replacement of all L-amino acids with D-amino acids. Both Land D-PLNC8 αβ caused rapid disruption of lipid membrane integrity and were effective against both susceptible and antibiotic resistant strains. the D-enantiomer was stable against proteolytic degradation by trypsin compared to the L-enantiomer. Of the truncated peptides, β1-22, β7-34 and β1-20 retained an inhibitory activity. The peptides diffused rapidly (2 min) through the bacterial cell wall and permeabilized the cell membrane, causing swelling with a disorganized peptidoglycan layer. Interestingly, sub-MIC concentrations of PLNC8 αβ substantially enhanced the effects of different antibiotics in an additive or synergistic manner. This study shows that PLNC8 αβ is active against Staphylococcus spp. and may be developed as adjuvant in combination therapy to potentiate the effects of antibiotics and reduce their overall use. Although antibiotics are the most effective treatment against bacteria of the genus Staphylococcus (including the species S. aureus and S. epidermidis), these opportunistic pathogens are one of the leading causes of severe bacterial infections in humans connected to chronic wounds and medical devices, e.g. catheters and prosthetic implants 1. These persistent infections are generally difficult to treat, which increases the risk for bacterial dissemination and development of systemic complications 2,3. Furthermore, considering the gradual increase in antimicrobial resistance, treatment may be even more difficult to achieve as the available options become limited 4. Consequently, there is an urgent need to find new approaches in human medicine against bacterial infections, and bacteriocins represent a promising avenue that requires more consideration 5,6. Bacteriocins are antimicrobial peptides that are produced by most microorganisms that contribute their defence mechanisms. These peptides are divided into class I-V based on their structural characteristics. Class I includes small peptides (<5 kDa) with unusual amino acids, such as lanthionine and β-methyllanthionine that are post-translationally introduced and class II peptides are synthesized in precursor forms and processed (<10 kDa), and includes bacteriocins composed of two peptides (class IIb), such as PLNC8 αβ. Class III bacteriocins are large (>10 kDa) and sensitive to heat, class IV are small (<10 kDa) and circular peptides. Class V are small (<5 kDa), circular or linear peptides that are characterized by containing cross-linkages between cysteine residu...

Plantaricin NC8 αβ prevents Staphylococcus aureus-mediated cytotoxicity and inflammatory responses of human keratinocytes

“…Development of non-conventional therapies would therefore be advantageous, and bacteriocins represent an interesting novel route as the next generation of antibacterial agents 17 , 24 . We have previously reported that PLNC8 αβ has antimicrobial activity against the gram negative bacterium P. gingivalis 25 and recently we found that PlnA, E, F, J, K, NC8 αβ of Lactobacillus plantarum are potent antimicrobials against Staphylococcus species 19 , 26 . The antimicrobial activity of PLNC8 αβ against S. aureus , both antibiotic-sensitive and resistant strains, was investigated to verify our previous findings 26 .…”

“…We have previously reported that PLNC8 αβ has antimicrobial activity against the gram negative bacterium P. gingivalis 25 and recently we found that PlnA, E, F, J, K, NC8 αβ of Lactobacillus plantarum are potent antimicrobials against Staphylococcus species 19 , 26 . The antimicrobial activity of PLNC8 αβ against S. aureus , both antibiotic-sensitive and resistant strains, was investigated to verify our previous findings 26 . Bacterial permeabilization by PLNC8 αβ was recorded within minutes, and the inhibitory and bactericidal concentrations of PLNC8 αβ were found to be the same for both strains.…”

Engineered Cationic Antimicrobial Peptides (eCAPs) to Combat Multidrug-Resistant Bacteria

“…An important trend in AMP development is the potential of AMPs to enhance the efficacy of traditional antibiotics when used in combination. Such synergistic properties may considerably contribute to the fight against antibiotic resistance by rendering the already-existing antibiotic arsenal more effective against MDR bacteria, as demonstrated by the polymyxins, murepavadin, and helical AMPs [ 106 , 107 , 108 , 109 , 110 ].…”

On the Role of Platelet-Generated Amyloid Beta Peptides in Certain Amyloidosis Health Complications

“…The main toxic effect that has been suggested is related to the excess Ca ++ permeability through these pores, which induces calcium dyshomeostasis ( 90 , 91 ). Other toxic agents may also enter the membrane aperture to kill the cell ( 179 ). In our experiments, the external membrane of the yeast was perforated by synthetic Aβ at a 5-mM concentration ( 40 ).…”