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1.
Microbiome ; 9(1): 180, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470652

RESUMO

BACKGROUND: Probiotics have been used to regulate the gut microbiota and physiology in various contexts, but their precise mechanisms of action remain unclear. RESULTS: By population genomic analysis of 418 Bifidobacterium longum strains, including 143 newly sequenced in this study, three geographically distinct gene pools/populations, BLAsia1, BLAsia2, and BLothers, were identified. Genes involved in cell wall biosynthesis, particularly peptidoglycan biosynthesis, varied considerably among the core genomes of the different populations, but accessory genes that contributed to the carbohydrate metabolism were significantly distinct. Although active transmission was observed inter-host, inter-country, inter-city, intra-community, and intra-family, a single B. longum clone seemed to reside within each individual. A significant negative association was observed between host age and relative abundance of B. longum, while there was a strong positive association between host age and strain genotype [e.g., single nucleotide polymorphisms in the arginine biosynthesis pathway]. Further animal experiments performed with the B. longum isolates via using a D-galactose-induced aging mouse model supported these associations, in which B. longum strains with different genotypes in arginine biosynthesis pathway showed divergent abilities on protecting against host aging possibly via their different abilities to modify the metabolism of gut microbes. CONCLUSIONS: This is the first known example of research on the evolutionary history and transmission of this probiotic species. Our results propose a new mechanistic insight for promoting host longevity via the informed use of specific probiotics or molecules. Video abstract.


Assuntos
Bifidobacterium longum , Microbioma Gastrointestinal , Probióticos , Sulfaleno , Envelhecimento , Animais , Galactose , Microbioma Gastrointestinal/genética , Humanos , Camundongos
2.
Commun Biol ; 4(1): 1140, 2021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34588600

RESUMO

Parkinson's disease (PD) is a chronic neurological disorder associated with the misfolding of alpha-synuclein (α-syn) into aggregates within nerve cells that contribute to their neurodegeneration. Recent evidence suggests α-syn aggregation may begin in the gut and travel to the brain along the vagus nerve, with microbes potentially a trigger initiating α-syn misfolding. However, the effects α-syn alterations on the gut virome have not been investigated. In this study, we show longitudinal faecal virome changes in rats administered either monomeric or preformed fibrils (PFF) of α-syn directly into their enteric nervous system. Differential changes in rat viromes were observed when comparing monomeric and PFF α-syn, with alterations compounded by the addition of LPS. Changes in rat faecal viromes were observed after one month and did not resolve within the study's five-month observational period. These results suggest that virome alterations may be reactive to host α-syn changes that are associated with PD development.

4.
J Appl Microbiol ; 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34370377

RESUMO

AIMS: Nisin is a bacteriocin with a broad spectrum of activity against Gram-positive bacteria. The aims were to assess nisin activity against Clostridioides difficile in a complex microbial environment and determine the minimum inhibitory concentration at which C. difficile growth is suppressed whilst having minimal impact on the faecal microbiota. METHODS AND RESULTS: Faecal slurries were prepared from fresh faecal samples and spiked with C. difficile (106  CFU per ml). Nisin was added to each fermentation at a range of concentrations from 0 to 500 µM. Following 24 h, 16S rRNA gene sequencing was performed, and the presence of viable C. difficile was assessed. There was no viable C. difficile detected in the presence of 50-500 µM nisin. There was a decrease in the diversity of the microbiota in a nisin dose-dependent manner. Nisin predominantly depleted the relative abundance of the Gram-positive bacteria whilst the relative abundance of Gram-negative bacteria such as Escherichia Shigella and Bacteroides increased. CONCLUSIONS: Using an ex vivo model of the colon, this study demonstrates the ability of purified nisin to selectively deplete C. difficile in a faecal microbial environment and establishes the minimum concentration at which this occurs whilst having a minimal impact on the composition of the microbiota. SIGNIFICANCE AND IMPACT OF THE STUDY: This study opens up the potential to use nisin as a therapeutic for clostridial gut infections.

5.
BMC Biol ; 19(1): 163, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34407825

RESUMO

BACKGROUND: The crAss-like phages are ubiquitous and highly abundant members of the human gut virome that infect commensal bacteria of the order Bacteroidales. Although incapable of lysogeny, these viruses demonstrate long-term persistence in the human gut microbiome, dominating the virome in some individuals. RESULTS: Here we show that rapid phase variation of alternate capsular polysaccharides in Bacteroides intestinalis cultures plays an important role in a dynamic equilibrium between phage sensitivity and resistance, allowing phage and bacteria to multiply in parallel. The data also suggests the role of a concomitant phage persistence mechanism associated with delayed lysis of infected cells, similar to carrier state infection. From an ecological and evolutionary standpoint, this type of phage-host interaction is consistent with the Piggyback-the-Winner model, which suggests a preference towards lysogenic or other "benign" forms of phage infection when the host is stably present at high abundance. CONCLUSION: Long-term persistence of bacteriophage and host could result from mutually beneficial mechanisms driving bacterial strain-level diversity and phage survival in complex environments.

7.
Appl Environ Microbiol ; 87(16): e0039121, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34105992

RESUMO

Antimicrobial peptides are evolving as novel therapeutic options against the increasing problem of multidrug-resistant microorganisms, and nisin is one such avenue. However, some bacteria possess a specific nisin resistance system (NSR), which cleaves the peptide reducing its bactericidal efficacy. NSR-based resistance was identified in strains of Streptococcus uberis, a ubiquitous pathogen that causes mastitis in dairy cattle. Previous studies have demonstrated that a nisin A derivative termed nisin PV, featuring S29P and I30V, exhibits enhanced resistance to proteolytic cleavage by NSR. Our objective was to investigate the ability of this nisin derivative to eradicate and inhibit biofilms of S. uberis DPC 5344 and S. uberis ATCC 700407 (nsr+) using crystal violet (biomass), 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) (viability) assays, and confocal microscopy (viability and architecture). When preestablished biofilms were assessed, both peptides reduced biofilm biomass by over 60% compared to that of the untreated controls. However, a 42% higher reduction in viability was observed following treatment with nisin PV compared to that of nisin A. Accordingly, confocal microscopy analysis revealed significantly more dead cells on the biofilm upper surface and a reduced thickness following treatment with nisin PV. When biofilm inhibition was assessed, nisin PV inhibited biofilm formation and decreased viability up to 56% and 85% more than nisin A, respectively. Confocal microscopy analysis revealed a lack of biofilm for S. uberis ATCC 700407 and only dead cells for S. uberis DPC 5344. These results suggest that nisin PV is a promising alternative to effectively reduce the biofilm formation of S. uberis strains carrying NSR. IMPORTANCE One of the four most prevalent species of bovine mastitis-causing pathogens is S. uberis. Its ability to form biofilms confers on the bacteria greater resistance to antibiotics, requiring higher doses to be more effective. In a bid to limit antibiotic resistance development, the need for alternative antimicrobials is paramount. Bacteriocins such as nisin represent one such alternative that could alleviate the impact of mastitis caused by S. uberis. However, many strains of S. uberis have been shown to possess nisin resistance determinants, such as the nisin resistance protein (NSR). In this study, we demonstrate the ability of nisin and a nisin derivative termed PV that is insensitive to NSR to prevent and remove biofilms of NSR-producing S. uberis strains. These findings will add new information to the antimicrobial bacteriocins and control of S. uberis research fields specifically in relation to biofilms and nsr+ mastitis-associated strains.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Nisina/química , Nisina/farmacologia , Streptococcus/efeitos dos fármacos , Bioengenharia , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Nisina/genética , Streptococcus/crescimento & desenvolvimento , Streptococcus/fisiologia
8.
Food Microbiol ; 99: 103835, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34119119

RESUMO

In this study, we examined the ability of nisin A and a rationally assembled bank of 36 nisin derivative producing Lactococcus lactis strains to inhibit Listeria. A broth-based bioluminescence assay for screening single and combinations of bioengineered nisin derivatives using cell-free supernatants (CFS) from nisin derivative producing strains was developed. In this way, we screened 630 combinations of nisin derivative producing strains, identifying two (CFS from M17Q + N20P and M17Q + S29E) which exhibited enhanced anti-listerial activity when used together compared to when used alone, or to the nisin A producing strain. Minimal inhibitory concentration assays performed with purified peptides revealed than when used singly, the specific activities of M17Q, N20P and S29E (3.75-7.5 µM) against L. innocua were equal to, or less than that of nisin A (MIC of 3.75 µM). Broth-based growth curve assays using purified peptides demonstrated that use of the double peptide combinations and a triple peptide combination (M17Q + N20P + S29E) resulted in an extended lag phase of L. innocua, while kill curve assays confirmed the enhanced bactericidal activity of the combinations in comparison to the single derivative peptides or nisin A. Furthermore, the enhanced activity of the M17Q + N20P combination was maintained in a model food system (frankfurter homogenate) at both chill (4 °C) and abusive (20 °C) temperature conditions, with final cell numbers significantly less (1-2 log10 CFU/ml) than those observed with the derivative peptides alone, or nisin A. To our knowledge, this study is the first investigation that combines bioengineered bacteriocins with the aim of discovering a combination with enhanced antimicrobial activity.


Assuntos
Antibacterianos/metabolismo , Antibacterianos/farmacologia , Lactococcus lactis/metabolismo , Listeria/efeitos dos fármacos , Nisina/metabolismo , Nisina/farmacologia , Antibacterianos/química , Bioengenharia , Lactococcus lactis/genética , Listeria/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Nisina/química , Nisina/genética
9.
Biochim Biophys Acta Rev Cancer ; 1876(1): 188572, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34082064

RESUMO

Pharmaceutical agents in oncology currently have high attrition rates from early to late phase clinical trials. Recent advances in computational methods, notably causal artificial intelligence, and availability of rich clinico-genomic databases have made it possible to simulate the efficacy of cancer drug protocols in diverse patient populations, which could inform and improve clinical trial design. Here, we review the current and potential use of in silico trials and causal AI to increase the efficacy and safety of traditional clinical trials. We conclude that in silico trials using causal AI approaches can simulate control and efficacy arms, inform patient recruitment and regimen titrations, and better enable subgroup analyses critical for precision medicine.


Assuntos
Antineoplásicos/uso terapêutico , Inteligência Artificial , Ensaios Clínicos como Assunto , Simulação por Computador , Genômica , Neoplasias/tratamento farmacológico , Medicina de Precisão , Projetos de Pesquisa , Antineoplásicos/efeitos adversos , Biomarcadores Tumorais/genética , Tomada de Decisão Clínica , Humanos , Terapia de Alvo Molecular , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia
11.
Int J Mol Sci ; 22(11)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073633

RESUMO

Clostridioides difficile is a spore-forming enteric pathogen causing life-threatening diarrhoea and colitis. Microbial disruption caused by antibiotics has been linked with susceptibility to, and transmission and relapse of, C. difficile infection. Therefore, there is an urgent need for novel therapeutics that are effective in preventing C. difficile growth, spore germination, and outgrowth. In recent years bacteriophage-derived endolysins and their derivatives show promise as a novel class of antibacterial agents. In this study, we recombinantly expressed and characterized a cell wall hydrolase (CWH) lysin from C. difficile phage, phiMMP01. The full-length CWH displayed lytic activity against selected C. difficile strains. However, removing the N-terminal cell wall binding domain, creating CWH351-656, resulted in increased and/or an expanded lytic spectrum of activity. C. difficile specificity was retained versus commensal clostridia and other bacterial species. As expected, the putative cell wall binding domain, CWH1-350, was completely inactive. We also observe the effect of CWH351-656 on preventing C. difficile spore outgrowth. Our results suggest that CWH351-656 has therapeutic potential as an antimicrobial agent against C. difficile infection.


Assuntos
Bacteriófagos , Clostridioides difficile , Endopeptidases/metabolismo , Esporos Bacterianos , Proteínas Virais/metabolismo , Bacteriófagos/enzimologia , Bacteriófagos/genética , Clostridioides difficile/enzimologia , Clostridioides difficile/genética , Clostridioides difficile/virologia , Endopeptidases/genética , Endopeptidases/farmacologia , Enterocolite Pseudomembranosa/tratamento farmacológico , Humanos , Esporos Bacterianos/enzimologia , Esporos Bacterianos/genética , Esporos Bacterianos/virologia , Proteínas Virais/genética , Proteínas Virais/farmacologia
12.
Gut Microbes ; 13(1): 1-13, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33970781

RESUMO

Adaptation to life in the deep-sea can be dramatic, with fish displaying behaviors and appearances unlike those seen in any other aquatic habitat. However, the extent of which adaptations may have developed at a microbial scale is not as clear. Shotgun metagenomic sequencing of the intestinal microbiome of 32 species of deep-sea fish from across the Atlantic Ocean revealed that many of the associated microbes differ extensively from those previously identified in reference databases. 111 individual metagenome-assembled genomes (MAGs) were constructed representing individual microbial species from the microbiomes of these fish, many of which are potentially novel bacterial taxa and provide a window into the microbial diversity in this underexplored environment. These MAGs also demonstrate how these microbes have adapted to deep-sea life by encoding a greater capacity for several cellular processes such as protein folding and DNA replication that can be inhibited by high pressure. Another intriguing feature was the almost complete lack of genes responsible for acquired resistance to known antibiotics in many of the samples. This highlights that deep-sea fish microbiomes may represent one of few animal-associated microbiomes with little influence from human activity. The ability of the microbes in these samples to bioluminesce is lower than expected given predictions that this trait has an important role in their life cycle at these depths. The study highlights the uniqueness, complexity and adaptation of microbial communities living in one of the largest and harshest environments on Earth.

13.
Ann Nutr Metab ; : 1-6, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34038906

RESUMO

In most instances where a pathogen has initiated an infection, the primary goal of the treating physician or pharmacist is to eliminate the pathogen. In the absence of knowledge of the precise identity of the problem-causing microbe, a broad-spectrum antimicrobial gives the best chance of success. This approach has saved many lives and is an invaluable tool in fighting infections. However, perhaps our current appreciation of the importance of the microbiome in human health should give us pause. We can regard the microbiome as a virtual organ within the human body, and we would surely hesitate to advance any therapeutic approach that would cause substantial damage to one of our organs. This is one consequence of many broad-spectrum antimicrobial therapies. There may be instances where a more precise approach would be useful. I have termed this "selective depletion"; a concept where pathogen numbers are curtailed by a narrow-spectrum inhibitor but the microbiome is protected and can play a role in restoring health and suppressing the outgrowth of the pathogen in the infected patient. It may well be that the best reservoir of microbiome-friendly antimicrobial agents is the microbiome itself, and I provide examples of where the microbiome has been mined for novel precision antimicrobials.

14.
Nat Rev Gastroenterol Hepatol ; 18(9): 649-667, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33948025

RESUMO

In 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of experts specializing in nutrition, microbial physiology, gastroenterology, paediatrics, food science and microbiology to review the definition and scope of postbiotics. The term 'postbiotics' is increasingly found in the scientific literature and on commercial products, yet is inconsistently used and lacks a clear definition. The purpose of this panel was to consider the scientific, commercial and regulatory parameters encompassing this emerging term, propose a useful definition and thereby establish a foundation for future developments. The panel defined a postbiotic as a "preparation of inanimate microorganisms and/or their components that confers a health benefit on the host". Effective postbiotics must contain inactivated microbial cells or cell components, with or without metabolites, that contribute to observed health benefits. The panel also discussed existing evidence of health-promoting effects of postbiotics, potential mechanisms of action, levels of evidence required to meet the stated definition, safety and implications for stakeholders. The panel determined that a definition of postbiotics is useful so that scientists, clinical triallists, industry, regulators and consumers have common ground for future activity in this area. A generally accepted definition will hopefully lead to regulatory clarity and promote innovation and the development of new postbiotic products.


Assuntos
Prebióticos , Probióticos , Conferências de Consenso como Assunto , Humanos , Sociedades Científicas
15.
Cell Rep ; 35(7): 109132, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34010651

RESUMO

The human gut microbiome consists of bacteria, archaea, eukaryotes, and viruses. The gut viruses are relatively underexplored. Here, we longitudinally analyzed the gut virome composition in 11 healthy adults: its stability, variation, and the effect of a gluten-free diet. Using viral enrichment and a de novo assembly-based approach, we demonstrate the quantitative dynamics of the gut virome, including dsDNA, ssDNA, dsRNA, and ssRNA viruses. We observe highly divergent individual viral communities, carrying on an average 2,143 viral genomes, 13.1% of which were present at all 3 time points. In contrast to previous reports, the Siphoviridae family dominates over Microviridae in studied individual viromes. We also show individual viromes to be stable at the family level but to vary substantially at the genera and species levels. Finally, we demonstrate that lower initial diversity of the human gut virome leads to a more pronounced effect of the dietary intervention on its composition.

17.
Viruses ; 13(4)2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33920965

RESUMO

Antibiotic-resistant pathogens are increasingly more prevalent and problematic. Traditional antibiotics are no longer a viable option for dealing with these multidrug-resistant microbes and so new approaches are needed. Bacteriophage-derived proteins such as endolysins could offer one effective solution. Endolysins are bacteriophage-encoded peptidoglycan hydrolases that act to lyse bacterial cells by targeting their cell's wall, particularly in Gram-positive bacteria due to their naturally exposed peptidoglycan layer. These lytic enzymes have received much interest from the scientific community in recent years for their specificity, mode of action, potential for engineering, and lack of resistance mechanisms. Over the past decade, a renewed interest in endolysin therapy has led to a number of successful applications. Recombinant endolysins have been shown to be effective against prominent pathogens such as MRSA, Listeria monocytogenes, Staphylococcus strains in biofilm formation, and Pseudomonas aeruginosa. Endolysins have also been studied in combination with other antimicrobials, giving a synergistic effect. Although endolysin therapy comes with some regulatory and logistical hurdles, the future looks promising, with the emergence of engineered "next-generation" lysins. This review will focus on the likelihood that endolysins will become a viable new antimicrobial therapy and the challenges that may have to be overcome along the way.


Assuntos
Endopeptidases/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Terapia por Fagos/métodos , Animais , Bacteriófagos/enzimologia , Parede Celular/metabolismo , Humanos , Peptidoglicano/metabolismo
18.
Microbiome ; 9(1): 89, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845877

RESUMO

BACKGROUND: The gut phageome comprises a complex phage community of thousands of individual strains, with a few highly abundant bacteriophages. CrAss-like phages, which infect bacteria of the order Bacteroidales, are the most abundant bacteriophage family in the human gut and make an important contribution to an individual's core virome. Based on metagenomic data, crAss-like phages form a family, with four sub-families and ten candidate genera. To date, only three representatives isolated in pure culture have been reported: ΦcrAss001 and two closely related phages DAC15 and DAC17; all are members of the less abundant candidate genus VI. The persistence at high levels of both crAss-like phage and their Bacteroidales hosts in the human gut has not been explained mechanistically, and this phage-host relationship can only be properly studied with isolated phage-host pairs from as many genera as possible. RESULTS: Faeces from a healthy donor with high levels of crAss-like phage was used to initiate a faecal fermentation in a chemostat, with selected antibiotics chosen to inhibit rapidly growing bacteria and selectively enrich for Gram-negative Bacteroidales. This had the objective of promoting the simultaneous expansion of crAss-like phages on their native hosts. The levels of seven different crAss-like phages expanded during the fermentation, indicating that their hosts were also present in the fermenter. The enriched supernatant was then tested against individual Bacteroidales strains isolated from the same faecal sample. This resulted in the isolation of a previously uncharacterised crAss-like phage of candidate genus IV of the proposed Alphacrassvirinae sub-family, ΦcrAss002, that infects the gut commensal Bacteroides xylanisolvens. ΦcrAss002 does not form plaques or spots on lawns of sensitive cells, nor does it lyse liquid cultures, even at high titres. In keeping with the co-abundance of phage and host in the human gut, ΦcrAss002 and Bacteroides xylanisolvens can also co-exist at high levels when co-cultured in laboratory media. CONCLUSIONS: We report the isolation and characterisation of ΦcrAss002, the first representative of the proposed Alphacrassvirinae sub-family of crAss-like phages. ΦcrAss002 cannot form plaques or spots on bacterial lawns but can co-exist with its host, Bacteroides xylanisolvens, at very high levels in liquid culture without impacting on bacterial numbers. Video abstract.


Assuntos
Bacteriófagos , Microbioma Gastrointestinal , Bacteriófagos/genética , Bacteroides , Humanos , Filogenia
19.
Int J Mol Sci ; 22(7)2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33801752

RESUMO

Bovine mastitis is a significant economic burden for dairy enterprises, responsible for premature culling, prophylactic and therapeutic antibiotic use, reduced milk production and the withholding (and thus wastage) of milk. There is a desire to identify novel antimicrobials that are expressly directed to veterinary applications, do not require a lengthy milk withholding period and that will not have a negative impact on the growth of lactic acid bacteria involved in downstream dairy fermentations. Nisin is the prototypical lantibiotic, a family of highly modified antimicrobial peptides that exhibit potent antimicrobial activity against many Gram-positive microbes, including human and animal pathogens including species of Staphylococcus and Streptococcus. Although not yet utilized in the area of human medicine, nisin is currently applied as the active agent in products designed to prevent bovine mastitis. Over the last decade, we have harnessed bioengineering strategies to boost the specific activity and target spectrum of nisin against several problematic microorganisms. Here, we screen a large bank of engineered nisin derivatives to identify novel derivatives that exhibit improved specific activity against a selection of staphylococci, including mastitis-associated strains, but have unchanged or reduced activity against dairy lactococci. Three such peptides were identified; nisin A M17Q, nisin A T2L and nisin A HTK.


Assuntos
Antibacterianos/farmacologia , Bacteriocinas/farmacologia , Lactococcus/efeitos dos fármacos , Mastite Bovina/microbiologia , Nisina/química , Staphylococcus/efeitos dos fármacos , Animais , Bioengenharia/métodos , Bovinos , Feminino , Testes de Sensibilidade Microbiana , Leite/microbiologia , Peptídeos/química , Engenharia de Proteínas/métodos
20.
Drug Deliv Transl Res ; 11(4): 1735-1751, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33876405

RESUMO

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.

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