Abstract
Lacticin 3147 is a dual-acting two-peptide bacteriocin which is generally active against Gram-positive bacteria, including Listeria monocytogenes and antimicrobial-resistant bacteria such as Closteroides difficile in the colon. L. monocytogenes infections can cause life-long effects in the elderly and vulnerable and can cause severe complications in pregnant women. C. difficile causes one of the most common healthcare-associated infections and can be fatal in vulnerable groups such as the elderly. Although lacticin 3147 is degraded by intestinal proteases and has poor aqueous solubility, encapsulation of the bacteriocin could enable its use as an antimicrobial for treating these bacterial infections locally in the gastrointestinal tract. Lacticin 3147 displayed activity in aqueous solutions at a range of pH values and in gastric and intestinal fluids. Exposure to trypsin and α-chymotrypsin resulted in complete inactivation, implying that lacticin 3147 should be protected from these enzymes to achieve successful local delivery to the gastrointestinal tract. The amount of lacticin 3147 dissolved, i.e. its solution concentration, in water or buffered solutions at pH 1.6 and 7.4 was low and varied with time but increased and was stabilized in gastrointestinal fluids by the phospholipid and bile salt components present. Thus, the feasibility of a solid lipid nanoparticle (SLN) delivery system for local administration of lacticin 3147 was investigated. Bacteriocin activity was observed after encapsulation and release from a lipid matrix. Moreover, activity was seen after exposure to degrading enzymes. Further optimization of SLN delivery systems could enable the successful pharmaceutical development of active lacticin 3147 as an alternative to traditional antibiotics.Graphical abstract
Highlights
Antimicrobial resistance (AMR) occurs when microorganisms evolve in ways that render antibiotics ineffective
Lacticin 3147′s activity against various strains including L. monocytogenes and C. difficile has been previously reported in the literature [11, 14,15,16, 33, 34]; for the purpose of this study, L. monocytogenes was used to establish the impact of solution composition, pH, and process parameters on its activity
Our studies found that lacticin 3147 fully inhibited L. monocytogenes ATCC1916 at a concentration as low as 0.99 μg/ml Ltnα and 0.85 μg/ml Ltnβ (300 nM) (Fig. 3a) via growth curve assays
Summary
Antimicrobial resistance (AMR) occurs when microorganisms evolve in ways that render antibiotics ineffective. The number of bacteria becoming resistant to antimicrobial. Cork, Ireland 5 SSPC the SFI Research Centre for Pharmaceuticals, University of Limerick, Limerick, Ireland drugs is rising constantly due to non-prudent use of antibiotics and the lack of new antimicrobials coming to the market [1,2,3]. It has been projected that by 2050 there could be 10 million deaths worldwide per annum due to AMR if this crisis is not tackled, exceeding the current number of deaths from cancer [4]. Alternatives to traditional antibiotics, such as bacteriocins, are being investigated. Bacteriocins are small, cationic, heat stable, polypeptides that are ribosomally produced by bacteria.
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