Enterocin DD14 can inhibit the infection of eukaryotic cells with enveloped viruses.

Bacteriocins are ribosomally synthesized bacterial peptides endowed with antibacterial, antiprotozoal, anticancer and antiviral activities. In the present study, we evaluated the antiviral activities of two bacteriocins, enterocin DD14 (EntDD14) and lacticaseicin 30, against herpes simplex virus type 1 (HSV-1), human coronavirus 229E (HCoV-229E) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Vero, Huh7 and Vero E6 cells, respectively. In addition, the interactions of these bacteriocins with the envelope glycoprotein D of HSV-1 and the receptor binding domains of HCoV-229E and SARS-CoV-2 have been computationally evaluated using protein-protein docking and molecular dynamics simulations. HSV-1 replication in Vero cells was inhibited by EntDD14 and, to a lesser extent, by lacticaseicin 30 added to cells after virus inoculation. EntDD14 and lacticaseicin 30 had no apparent antiviral activity against HCoV-229E; however, EntDD14 was able to inhibit SARS-CoV-2 in Vero E6 cells. Further studies are needed to elucidate the antiviral mechanism of these bacteriocins.

Biopreservation of Fresh Sardines (Sardina pilchardus) Using Lactiplantibacillus plantarum OV50 Isolated from Traditional Algerian Green Olives Preparations.

Lactiplantibacillus plantarum OV50 is a novel strain that was isolated from Algerian olives. Prior to its use as a natural biopreservative, OV50 underwent characterization for various functions. OV50 shows no proteolytic, lipolytic, or hemolytic activity. In addition, it is non-cytotoxic to eukaryotic cells and does not exhibit acquired antibiotic resistance. OV50 was tested with Pseudomonas aeruginosa ATCC 27835, Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 8739, and Vibrio cholerae ATCC 14035 in a sardine based-medium at 37 °C and 7 °C. At 37 °C, OV50 completely inhibited the growth of these foodborne pathogens for a maximum of 6 h. At 7 °C, it suppressed their growth for a maximum of 8 days, except for S. aureus ATCC 6538, whose growth was reduced from 4 to 2 log CFU/mL. Microbiological counts, total volatile basic nitrogen (TVB-N), and peroxide values (PV) concentrations were determined in fresh sardines inoculated with OV50 and kept at 7 °C for 12 days. The inoculated sardines showed a significant reduction in TVB-N levels at D8 (34.9 mg/100 g) compared to the control (59.73 mg/100 g) and in PV concentrations at D4 (6.67 meq/kg) compared to the control (11.44 meq/kg), as well as a significant reduction in the numbers of Enterobacterales, Coliforms, Pseudomonas spp., Vibrio spp., and S. aureus At D8 and D12 compared to the control. Taken together, these results indicate that OV50 can improve the microbiological safety, freshness, and quality of sardines.

Assessment of safety and in situ antibacterial activity of Weissella cibaria strains isolated from dairy farms in Minas Gerais State, Brazil, for their food application.

Weissella cibaria W21, W25, and W42 strains have previously been characterized for their antagonism against a range of foodborne pathogens. However, prior to their use as protective agents, further analyses such as their safety and in situ activity are needed. The safety of W. cibaria W21, W25, and W42 strains was predicted in silico and confirmed experimentally. Analyses of their genomes using appropriate software did not reveal any acquired antimicrobial resistance genes, nor mobile genetic elements (MGEs). The survival of each strain was determined in vitro under conditions mimicking the gastrointestinal tract (GIT). Thus, hemolysis analysis was performed using blood agar and the cytotoxicity assay was determined using a mixture of two cell lines (80% of Caco-2 and 20% of HT-29). We also performed the inflammation and anti-inflammation capabilities of these strains using the promonocytic human cell line U937. The Weissella strains were found to be haemolysis-negative and non-cytotoxic and did not induce any inflammation. Furthermore, these strains adhered tightly to intestinal Caco-2 cell-lines and exerted in situ anti-proliferative activity against methicillin-resistant Staphylococcus aureus (strain MRSA S1) and Escherichia coli 181, a colistin-resistant strain. However, the W. cibaria strains showed low survival rate under simulated GIT conditions in vitro. The unusual LAB-strains W. cibaria strains W21, W25, and W42 are safe and endowed with potent antibacterial activities. These strains are therefore good candidates for industrial applications. The results of this study provide a characterization and insights into Weissella strains, which are considered unusual LAB, but which prompt a growing interest in their bio-functional properties and their potential industrial applications.

Lack of PNPase activity in Enterococcus faecalis 14 increases the stability of EntDD14 bacteriocin transcripts.

A mutant deficient in polynucleotide phosphorylase (PNPase) activity was previously constructed in Enterococcus faecalis 14; a strain producing a leaderless two-peptide enterocin DD14 (EntDD14). Here, we examined the impact of the absence of PNPase on the expression and synthesis of EntDD14, at the transcriptional and functional levels. As result, EntDD14 synthesis augmented in line with the growth curve, reaching a two- to fourfold increase in the ΔpnpA mutant compared to the E. faecalis 14 wild-type strain (WT). EntDD14 synthesis has reached its highest level after 9 h of growth in both strains. Notably, high expression level of the ddABCDEFGHIJ cluster was registered in ΔpnpA mutant. Transcriptional and in silico analyses support the existence of ddAB and ddCDEFGHIJ independent transcripts, and analysis of the fate of ddAB and ddCDEFGHIJ mRNAs indicated that the differences in mRNA levels and the high EntDD14 activity are likely due to a better stability of the two transcripts in the ΔpnpA mutant, which should result in a higher translation efficiency of the ddAB EntDD14 structural genes and their other protein determinants. Consequently, this study shows a potential link between the mRNA stability and EntDD14 synthesis, secretion and immunity in a genetic background lacking PNPase.

A Review on Enterocin DD14, the Leaderless Two-Peptide Bacteriocin with Multiple Biological Functions and Unusual Transport Pathway.

Enterocin DD14 (EntDD14) is a two-peptide leaderless bacteriocin (LLB) produced by Enterococcus faecalis 14, a human strain isolated from meconium. Studies performed on EntDD14 enabled it to show its activity against Gram-positive bacteria such as Listeria monocytogenes, Clostridium perfringens, Enterococcus faecalis, and Staphylococcus aureus. EntDD14 was also shown to potentiate the activity of different antibiotics such as erythromycin, kanamycin, and methicillin when assessed against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo in the NMRI-F holoxenic mouse model. Additionally, EntDD14 has an antiviral activity and decreased the secretion of pro-inflammatory IL-6 and IL-8 in inflamed human intestinal Caco-2 cells. The genome of E. faecalis 14 was sequenced and annotated. Molecular tools such as Bagel4 software enabled us to locate a 6.7kb-EntDD14 cluster. Transport of EntDD14 outside of the cytoplasm was shown to be performed synergistically by a channel composed of two pleckstrin-homology-domain-containing proteins, namely DdE/DdF and the ABC transporter DdGHIJ. This latter could also protect the bacteriocinogenic strain against extracellular EntDD14. Here, we focus on academic data and potential therapeutic issues of EntDD14, as a model of two-peptide LLB.

Advances in Characterizing the Transport Systems of and Resistance to EntDD14, A Leaderless Two-Peptide Bacteriocin with Potent Inhibitory Activity.

Enterocin DD14 (EntDD14) is a two-peptide leaderless bacteriocin produced by the Enterococcus faecalis 14 strain previously isolated from meconium. This bacteriocin is mainly active against Gram-positive bacteria. Leaderless bacteriocins do not undergo post-translational modifications and are therefore immediately active after their synthesis. As a result, the cells that produce such bacteriocins have developed means of protection against them which often involve transport systems. In this and our previous work, we constructed different mutants deleted in the genes involved in the transport functions, thus covering all the supposed components of this transport system, using Listeria innocua ATCC 33090 as the indicator strain to assess the activity of externalized EntDD14. We also assessed the self-resistance of the WT and all its engineered derivative mutants against EntDD14, provided extracellularly, in order to evaluate their self-resistance. The results obtained highlight that the ABC transporter constituted by the DdG, H, I, and J proteins contributes to EntDD14 export as well as resistance to an external supply of EntDD14. Our results also have established the essential role of the DdE and DdF proteins as primary transporters dedicated to the externalization of EntDD14. Moreover, the in silico data showed that DdE and DdF appear to assemble in a formation that forms an essential channel for the exit of EntDD14. This channel DdEF may interact with the ABC transporter DdGHIJ in order to control the flow of bacteriocin across the membrane, although the nature of this interaction remains to be elucidated.

Antimicrobial Properties, Functional Characterisation and Application of Fructobacillus fructosus and Lactiplantibacillus plantarum Isolated from Artisanal Honey.

Honey is a valuable reservoir of lactic acid bacteria (LAB) and, particularly, of fructophilic LAB (FLAB), a relatively novel subgroup of LAB whose functional potential for human and food application has yet to be explored. In this study, FLAB and LAB strains have been isolated from honeys of different floral origins and selected for their broad antimicrobial activity against typical foodborne pathogenic bacteria and spoilage filamentous fungi. The best candidates, two strains belonging to the species Lactiplantibacillus plantarum and Fructobacillus fructosus, were submitted to partial characterisation of their cell free supernatants (CFS) in order to identify the secreted metabolites with antimicrobial activity. Besides, these strains were examined to assess some major functional features, including in vitro tolerance to the oro-gastrointestinal conditions, potential cytotoxicity against HT-29 cells, adhesion to human enterocyte-like cells and capability to stimulate macrophages. Moreover, when the tested strains were applied on table grapes artificially contaminated with pathogenic bacteria or filamentous fungi, they showed a good ability to antagonise the growth of undesired microbes, as well as to survive on the fruit surface at a concentration that is recommended to develop a probiotic effect. In conclusion, both LAB and FLAB honey-isolated strains characterised in this work exhibit functional properties that validate their potential use as biocontrol agents and for the design of novel functional foods. We reported antimicrobial activity, cytotoxic evaluation, probiotic properties and direct food application of a F. fructosus strain, improving the knowledge of this species, in particular, and on FLAB, more generally.

Impact of Dietary Regime and Seasonality on Hindgut's Mycobiota Diversity in Dairy Cows.

We describe and discuss the intestinal mycobiota of dairy cows reared in France following variations in dietary regimes and two seasons. Two groups of 21 animals were followed over a summer and winter period, and another group of 28 animals was followed only during the same summer season. The summer diet was based on grazing supplemented with 3-5 kg/d of maize, grass silage and hay, while the winter diet consisted of 30% maize silage, 25% grass silage, 15% hay and 30% concentrate. A total of 69 DNA samples were extracted from the feces of these cows. Amplification and sequencing of the ITS2 region were used to assess mycobiota diversity. Analyses of alpha and beta diversity were performed and compared statistically. The mycobiota changed significantly from summer to winter conditions with a decrease in its diversity, richness and evenness parameters, while beta diversity analysis showed different mycobiota profiles. Of note, the Geotrichum operational taxonomic unit (OTU) was prevalent in the winter group, with a mean relative abundance (RA) of 65% of the total mycobiota. This Geotrichum OTU was also found in the summer group, but to a lesser extent (5%). In conclusion, a summer grazing diet allowed a higher fecal fungal diversity. These data show, for the first time, that a change in diet associated with seasonality plays a central role in shaping hindgut fungal diversity.

Structure of Lacticaseicin 30 and Its Engineered Variants Revealed an Interplay between the N-Terminal and C-Terminal Regions in the Activity against Gram-Negative Bacteria.

Lacticaseicin 30 is one of the five bacteriocins produced by the Gram-positive Lacticaseibacillus paracasei CNCM I-5369. This 111 amino acid bacteriocin is noteworthy for being active against Gram-negative bacilli including Escherichia coli strains resistant to colistin. Prediction of the lacticaseicin 30 structure using the Alphafold2 pipeline revealed a largely helical structure including five helix segments, which was confirmed by circular dichroism. To identify the structural requirements of the lacticaseicin 30 activity directed against Gram-negative bacilli, a series of variants, either shortened or containing point mutations, was heterologously produced in Escherichia coli and assayed for their antibacterial activity against a panel of target strains including Gram-negative bacteria and the Gram-positive Listeria innocua. Lacticaseicin 30 variants comprising either the N-terminal region (amino acids 1 to 39) or the central and C-terminal regions (amino acids 40 to 111) were prepared. Furthermore, mutations were introduced by site-directed mutagenesis to obtain ten bacteriocin variants E6G, T7P, E32G, T33P, T52P, D57G, A74P, Y78S, Y93S and A97P. Compared to lacticaseicin 30, the anti-Gram-negative activity of the N-terminal peptide and variants E32G, T33P and D57G remained almost unchanged, while that of the C-terminal peptide and variants E6G, T7P, T52P, A74P, Y78S, Y93S and A97P was significantly altered. Finally, the N-terminal region was further shortened to keep only the first 20 amino acid part that was predicted to include the first helix. The anti-Gram-negative activity of this truncated peptide was completely abolished. Overall, this study shows that activity of lacticaseicin 30, one of the rare Gram-positive bacteriocins inhibiting Gram-negative bacteria, requires at least two helices in the N-terminal region and that the C-terminal region carries amino acids playing a role in modulation of the activity. Taken together, these data will help to design forthcoming variants of lacticaseicin 30 as promising therapeutic agents to treat infections caused by Gram-negative bacilli.

Enhancing Colistin Activity against Colistin-Resistant Escherichia coli through Combination with Alginate Nanoparticles and Small Molecules.

Bacterial resistance to antibiotics has become a major public health problem worldwide, with the yearly number of deaths exceeding 700,000. To face this well-acknowledged threat, new molecules and therapeutic methods are considered. In this context, the application of nanotechnology to fight bacterial infection represents a viable approach and has experienced tremendous developments in the last decades. Escherichia coli (E. coli) is responsible for severe diarrhea, notably in the breeding sector, and especially in pig farming. The resulting infection (named colibacillosis) occurs in young piglets and could lead to important economic losses. Here, we report the design of several new formulations based on colistin loaded on alginate nanoparticles (Alg NPs) in the absence, but also in the presence, of small molecules, such as components of essential oils, polyamines, and lactic acid. These new formulations, which are made by concomitantly binding colistin and small molecules to Alg NPs, were successfully tested against E. coli 184, a strain resistant to colistin. When colistin was associated with Alg NPs, the minimal inhibition concentration (MIC) decreased from 8 to 1 µg/mL. It is notable that when menthol or lactic acid was co-loaded with colistin on Alg NPs, the MIC of colistin drastically decreased, reaching 0.31 or 0.62 µg/mL, respectively. These novel bactericidal formulations, whose innocuity towards eukaryotic HT-29 cells was established in vitro, are presumed to permeabilize the bacterial membrane and provoke the leakage of intracellular proteins. Our findings revealed the potentiating effect of the Alg NPs on colistin, but also of the small molecules mentioned above. Such ecological and economical formulations are easy to produce and could be proposed, after confirmation by in vivo and toxicology tests, as therapeutic strategies to replace fading antibiotics.

Enhanced Antibacterial Activity of Dermaseptin through Its Immobilization on Alginate Nanoparticles-Effects of Menthol and Lactic Acid on Its Potentialization.

Dermaseptin B2 (DRS-B2) is an antimicrobial peptide secreted by Phyllomedusa bicolor, which is an Amazonian tree frog. Here, we show that the adsorption of DRS-B2 on alginate nanoparticles (Alg NPs) results in a formulation (Alg NPs + DRS-B2) with a remarkable antibacterial activity against Escherichia coli ATCC 8739 and E. coli 184 strains, which are sensitive and resistant, respectively, to colistin. The antibacterial activity, obtained with this new formulation, is higher than that obtained with DRS-B2 alone. Of note, the addition of lactic acid or menthol to this new formulation augments its antibacterial activity against the aforementioned Gram-negative bacilli. The safety of DRS-B2, and also that of the new formulation supplemented or not with a small molecule such as lactic acid or menthol has been proven on the human erythrocytes and the eukaryotic cell line types HT29 (human) and IPEC-1 (animal). Similarly, their stability was determined under the conditions mimicking the gastrointestinal tract with different conditions: pH, temperature, and the presence of digestive enzymes. Based on all the obtained data, we assume that these new formulations are promising and could be suggested, after in vivo approval and completing regulation aspects, as alternatives to antibiotics to fight infections caused by Gram-negative bacilli such as E. coli.

The absence of PNPase activity in Enterococcus faecalis results in alterations of the bacterial cell-wall but induces high proteolytic and adhesion activities.

Enterococci are lactic acid bacteria (LAB) used as starters and probiotics, delineating their positive attributes. Nevertheless, enterococci can be culprit for thousands of infectious diseases, including urinary tract infections, bacteremia and endocarditis. Here, we aim to determine the impact of polynucleotide phosphorylase (PNPase) in the biology of Enterococcus faecalis 14; a human isolate from meconium. Thus, a mutant strain deficient in PNPase synthesis, named ΔpnpA mutant, was genetically obtained. After that, a transcriptomic study revealed a set of 244 genes differentially expressed in the ΔpnpA mutant compared with the wild-type strain, when exploiting RNAs extracted from these strains after 3 and 6 h of growth. Differentially expressed genes include those involved in cell wall synthesis, adhesion, biofilm formation, bacterial competence and conjugation, stress response, transport, DNA repair and many other functions related to the primary and secondary metabolism of the bacteria. Moreover, the ΔpnpA mutant showed an altered cell envelope ultrastructure compared with the WT strain, and is also distinguished by a strong adhesion capacity on eukaryotic cell as well as a high proteolytic activity. This study, which combines genetics, physiology and transcriptomics enabled us to show further biological functions that could be directly or indirectly controlled by the PNPase in E. faecalis 14.

Anti-adhesion and Anti-inflammatory Potential of the Leaderless Class IIb Bacteriocin Enterocin DD14.

In this study, we investigate the interactions between the leaderless class IIb bacteriocin, enterocin DD14 (EntDD14), or the methicillin or the combination of these antibacterials, and two methicillin-resistant Staphylococcus aureus strains (MRSA-S1 and USA 300) which are respectively a clinical strain and a reference strain. The results obtained showed that EntDD14 alone or in combination with the antibiotic could significantly prevent the adhesion of these pathogenic bacteria to human cells. On the other hand, we investigated the anti-inflammatory effect of EntDD14 on the secretion of pro-inflammatory interleukins, including IL-6 and IL-8. The results show that EntDD14 is able to decrease significantly the secretion of both interleukins on Caco-2 cells following their treatments with lipopolysaccharides. These novel data provide insightful informations to support applications of bacteriocins as therapeutic agents capable as well to defeat pathogenic bacteria and concomitantly limit their inflammatory reactions.

Genomic Analyses of Weissella cibaria W25, a Potential Bacteriocin-Producing Strain Isolated from Pasture in Campos das Vertentes, Minas Gerais, Brazil.

Weissella is a genus containing Gram-positive, heterofermentative bacteria belonging to the lactic acid bacteria (LAB) group. These bacteria are endowed with promising technological and antimicrobial attributes. Weissella cibaria W25 was isolated from a dairy environment where raw milk cheeses are produced. Therefore, we sequenced and assembled the W25 draft genome sequence, which consists of 41 contigs totaling ~2.4 Mbp, with a G + C content of 45.04%. Then we carried out a comprehensive comparative genomic analysis with W. cibaria 110, known to produce the weissellicin 110 bacteriocin, and four other non-bacteriocin-producing W. cibaria strains.

Impact of colistin and colistin-loaded on alginate nanoparticles on pigs infected with a colistin-resistant enterotoxigenic Escherichia coli strain.

Colistin is frequently used for the control of post-weaning diarrhoea in pigs. Colistin resistance caused by plasmidic genes is a public health issue. We evaluated, in experimental animal facilities, whether free colistin or colistin-loaded on alginate nanoparticles (colistin/Alg NPs) could select a colistin-resistant Enterotoxigenic Escherichia coli. The Alg NPs were produced by a simple top-down approach through ball milling of sodium alginate polymer precursor, and colistin loading was achieved through physical adsorption. Colistin loading on Alg NPs was confirmed using various tools such Fourier transform infrared spectroscopy and dynamic light scattering measurements. Thirty-four piglets were orally inoculated or not with a mcr-1-positive, rifampicin-resistant enterotoxigenic E. coli strain, and the inoculated pigs were either treated or not during five days with commercial colistin (100,000 IU/kg) or colistin/Alg NPs (40,415 IU/kg). Clinical signs were recorded. Fecal and post-mortem samples were analyzed by culture. The result clearly indicated that colistin/Alg NPs had a slightly better therapeutic effect. Both treatments led to a transitory decrease of the total E. coli fecal population with a majority of colistin-resistant E. coli isolates during treatment, but the dominant E. coli population was found susceptible at the end of the trial. Further studies are needed to evaluate, in diverse experimental or field conditions, the therapeutic efficacy of colistin/Alg NPs for post-weaning diarrhoea.

Protective Effects of Novel Lactobacillaceae Strains Isolated from Chicken Caeca against Necrotic Enteritis Infection: In Vitro and In Vivo Evidences.

The present study aimed to show the benefits of novel lactic acid bacteria (LAB) strains isolated from the caeca of healthy chickens. These novel strains, identified as Limosilactobacillus reuteri and Ligilactobacillus salivarius, displayed high levels of lactic acid production, capability of biofilm formation, high aggregation and adhesion scores, and significant survival rates under conditions mimicking the chicken gastrointestinal tract (GIT). In addition, these novel Lactobacillaceae isolates were neither hemolytic nor cytotoxic. In vivo trials were able to establish their ability to reduce necrotic enteritis. Notably, a significant weight gain was registered, on day 10 of treatment, in the group of chickens fed with a mixture of L. reuteri ICVB416 and L. salivarius ICVB430 strains, as compared with the control group. This group has also shown a reduced number of lesions in the gut compared with other infected chicken groups. This study provides in vitro and in vivo evidence supporting the benefits of these novel Lactobacillaceae isolates for their use in poultry livestock as protective cultures to control the bacterial necrotic enteritis (NE) Clostridium perfringens.

Evidence for the Involvement of Pleckstrin Homology Domain-Containing Proteins in the Transport of Enterocin DD14 (EntDD14); a Leaderless Two-Peptide Bacteriocin.

Bacteriocins synthesis is initiated from an inactive precursor, which is composed of an N-terminal leader peptide attached to a C-terminal pro-peptide. However, leaderless bacteriocins (LLB) do not possess this N-terminal leader peptide nor undergo post-translational modifications. These atypical bacteriocins are observed to be immediately active after their translation in the cytoplasm. However, although considered to be simple, the biosynthetic pathway of LLB remains to be fully understood. Enterocin DD14 (EntDD14) is a two-peptide LLB produced by Enterococcus faecalis 14, which is a strain isolated from meconium. In silico analysis of DNA encoding EntDD14 located a cluster of 10 genes ddABCDEFGHIJ, where ddE and ddF encode the peculiar DdE and DdF proteins, carrying pleckstrin homology (PH) domains. These modules are quite common in Eucarya proteins and are known to be involved in intracellular signaling or cytoskeleton organization. To elucidate their role within the EntDD14 genetic determinants, we constructed deletion mutants of the ddE and ddF genes. As a result, the mutants were unable to export EntDD14 outside of the cytoplasm even though there was a clear expression of structural genes ddAB encoding EntDD14, and genes ddHIJ encoding an ABC transporter. Importantly, in these mutant strains (ΔddE and ΔddF), EntDD14 was detected by mass spectrometry in the intracellular soluble fraction exerting, upon its accumulation, a toxic effect on the producing strain as revealed by cell-counting and confocal microscopy analysis. Taken together, these results clearly indicate that PH domain-containing proteins, such as DdE and DdF, are involved in the transport of the leaderless two-peptide EntDD14.

Bioprospecting Antimicrobials from Lactiplantibacillus plantarum: Key Factors Underlying Its Probiotic Action.

Lactiplantibacillus plantarum (L. plantarum) is a well-studied and versatile species of lactobacilli. It is found in several niches, including human mucosal surfaces, and it is largely employed in the food industry and boasts a millenary tradition of safe use, sharing a long-lasting relationship with humans. L. plantarum is generally recognised as safe and exhibits a strong probiotic character, so that several strains are commercialised as health-promoting supplements and functional food products. For these reasons, L. plantarum represents a valuable model to gain insight into the nature and mechanisms of antimicrobials as key factors underlying the probiotic action of health-promoting microbes. Probiotic antimicrobials can inhibit the growth of pathogens in the gut ensuring the intestinal homeostasis and contributing to the host health. Furthermore, they may be attractive alternatives to conventional antibiotics, holding potential in several biomedical applications. The aim of this review is to investigate the most relevant papers published in the last ten years, bioprospecting the antimicrobial activity of characterised probiotic L. plantarum strains. Specifically, it focuses on the different chemical nature, the action spectra and the mechanisms underlying the bioactivity of their antibacterial and antiviral agents. Emerging trends in postbiotics, some in vivo applications of L. plantarum antimicrobials, including strengths and limitations of their therapeutic potential, are addressed and discussed.

Current Knowledge of the Mode of Action and Immunity Mechanisms of LAB-Bacteriocins.

Bacteriocins produced by lactic acid bacteria (LAB-bacteriocins) may serve as alternatives for aging antibiotics. LAB-bacteriocins can be used alone, or in some cases as potentiating agents to treat bacterial infections. This approach could meet the different calls and politics, which aim to reduce the use of traditional antibiotics and develop novel therapeutic options. Considering the clinical applications of LAB-bacteriocins as a reasonable and desirable therapeutic approach, it is therefore important to assess the advances achieved in understanding their modes of action, and the resistance mechanisms developed by the producing bacteria to their own bacteriocins. Most LAB-bacteriocins act by disturbing the cytoplasmic membrane through forming pores, or by cell wall degradation. Nevertheless, some of these peptides still have unknown modes of action, especially those that are active against Gram-negative bacteria. Regarding immunity, most bacteriocin-producing strains have an immunity mechanism involving an immunity protein and a dedicated ABC transporter system. However, these immunity mechanisms vary from one bacteriocin to another.

High association of COVID-19 severity with poor gut health score in Lebanese patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has affected millions of lives globally. However, the disease has presented more extreme challenges for developing countries that are experiencing economic crises. Studies on COVID-19 symptoms and gut health are scarce and have not fully analyzed possible associations between gut health and disease pathophysiology. Therefore, this study aimed to demonstrate a potential association between gut health and COVID-19 severity in the Lebanese community, which has been experiencing a severe economic crisis. METHODS: This cross-sectional study investigated SARS-CoV-2 PCR-positive Lebanese patients. Participants were interviewed and gut health, COVID-19 symptoms, and different metrics were analyzed using simple and multiple logistic regression models. RESULTS: Analysis of the data showed that 25% of participants were asymptomatic, while an equal proportion experienced severe symptoms, including dyspnea (22.7%), oxygen need (7.5%), and hospitalization (3.1%). The mean age of the participants was 38.3 ±0.8 years, and the majority were males (63.9%), married (68.2%), and currently employed (66.7%). A negative correlation was found between gut health score and COVID-19 symptoms (Kendall's tau-b = -0.153, P = 0.004); indicating that low gut health was associated with more severe COVID-19 cases. Additionally, participants who reported unhealthy food intake were more likely to experience severe symptoms (Kendall's tau-b = 0.118, P = 0.049). When all items were taken into consideration, multiple ordinal logistic regression models showed a significant association between COVID-19 symptoms and each of the following variables: working status, flu-like illness episodes, and gut health score. COVID-19 severe symptoms were more common among patients having poor gut health scores (OR:1.31, 95%CI:1.07-1.61; P = 0.008), experiencing more than one episode of flu-like illness per year (OR:2.85, 95%CI:1.58-5.15; P = 0.001), and owning a job (OR:2.00, 95%CI:1.1-3.65; P = 0.023). CONCLUSIONS: To our knowledge, this is the first study that showed the impact of gut health and exposure to respiratory viruses on COVID-19 severity in Lebanon. These findings can facilitate combating the pandemic in Lebanon.