Type-I interferon (IFN-I) cytokines are produced by immune cells in response to microbial infections, cancer and autoimmune diseases, and subsequently, trigger cytoprotective and antiviral responses through the activation of IFN-I stimulated genes (ISGs). The ability of intestinal microbiota to modulate innate immune responses is well known, but the mechanisms underlying such responses remain elusive. Here we report that the intracellular sensors stimulator of IFN genes (STING) and mitochondrial antiviral signaling (MAVS) are essential for the production of IFN-I in response to lactic acid bacteria (LAB), common gut commensal bacteria with beneficial properties. Using human macrophage cells we show that LAB strains that potently activate the inflammatory transcription factor NF-κB are poor inducers of IFN-I and conversely, those triggering significant amounts of IFN-I fail to activate NF-κB. This IFN-I response is also observed in human primary macrophages, which modulate CD64 and CD40 upon challenge with IFN-I-inducing LAB. Mechanistically, IFN-I inducers interact more intimately with phagocytes as compared to NF-κB-inducers, and fail to activate IFN-I in the presence of phagocytosis inhibitors. These bacteria are then sensed intracellularly by the cytoplasmic sensors STING and, to a lesser extent, MAVS. Accordingly, macrophages deficient for STING showed dramatically reduced phosphorylation of TANK-binding kinase (TBK)-1 and IFN-I activation, which resulted in lower expression of ISGs. Our findings demonstrate a major role for intracellular sensing and STING in the production of IFN-I by beneficial bacteria and the existence of bacteria-specific immune signatures, which can be exploited to promote cytoprotective responses and prevent overreactive NF-κB-dependent inflammation in the gut.

Minimal processing for microbial decontamination, such as the use of natural antimicrobials, is gaining interest in the food industry as these methods are generally milder than conventional processing, therefore better maintaining the nutritional content and sensory characteristics of food products. The aim of this study was to quantify the impact of (i) structural composition and complexity, (ii) growth location and morphology, and (iii) the natural antimicrobial nisin, on the microbial dynamics of Listeria innocua. More specifically, viscoelastic food model systems of various compositions and internal structure were developed and characterised, i.e. monophasic Xanthan gum-based and biphasic Xanthan gum/Whey protein-based viscoelastic systems. The microbial dynamics of L. innocua at 10 °C, 30 °C and 37 °C were monitored and compared for planktonic growth in liquid, or in/on (immersed or surface colony growth) the developed viscoelastic systems, with or without a sublethal concentration of nisin. Microscopy imaging was used to determine the bacterial colony size and spatial organisation in/on the viscoelastic systems. Selective growth of L. innocua on the protein phase of the developed biphasic system was observed for the first time. Additionally, significant differences were observed in the colony size and distribution in the monophasic Xanthan gum-based systems depending on (i) the type of growth (surface/immersed) and (ii) the Xanthan gum concentration. Furthermore, the system viscosity in monophasic Xanthan gum-based systems had a protective role against the effects of nisin for immersed growth, and a further inhibitory effect for surface growth at a suboptimal temperature (10 °C). These findings give a systematic quantitative insight on the impact of nisin as an environmental challenge on the growth and spatial organisation of L. innocua, in viscoelastic food model systems of various structural compositions/complexities. This study highlights the importance of accounting for system structural composition/complexity when designing minimal food processing methods with natural antimicrobials.

Calcium phosphate glasses are a promising new generation of biomaterials that can simultaneously induce tissue regeneration and controlled release of therapeutic molecules. In this work, novel calcium phosphate glasses containing 0, 2, 4, and 6 mol % Cu 2+ were synthesized via room temperature precipitation reaction in aqueous solution. The effect of Cu 2+ addition on the glass properties and structure was investigated using thermal analysis, 31 P solidstate MAS NMR, Raman spectroscopy, and X-ray diffraction. All glasses crystallize at temperature >500°C and are mainly formed by Q 1 groups. The release of P, Ca, and Cu in solution over time was monitored via inductively coupled plasma-optical emission spectroscopy. It was found that with increasing Cu content, the amount of P and Ca released decreases whereas the amount of Cu released increases. The effect of Cu 2+ release on the antibacterial activity against S. aureus, a bacterial strain commonly found in postsurgery infections, has been investigated. The addition of copper has been shown to infer the glasses antibacterial properties. As expected, the antibacterial activity of the glasses increases with increasing Cu 2+ content. Cytocompatibility was assessed by seeding human osteoblast-like osteosarcoma cells Saos-2 (HTB85) on the glass particles. A significant increase in cell number was observed in all the glasses investigated. The copper-doped calcium phosphate glasses have proven to be multifunctional, as they combine bone regenerative properties with antibacterial activity. Therefore, they have great potential as antibacterial bioresorbable materials for hard tissue regeneration.

Dietary protein insufficiency has been linked to excessive TAG storage and non-alcoholic fatty liver disease (NAFLD) in developing countries. Hepatic TAG accumulation following a low-protein diet may be due to altered peroxisomal, mitochondrial and gut microbiota function. Hepatic peroxisomes and mitochondria normally mediate metabolism of nutrients to provide energy and substrates for lipogenesis. Peroxisome biogenesis and activities can be modulated by odd-chain fatty acids (OCFA) and SCFA that are derived from gut bacteria, for example, propionate and butyrate. Also produced during amino acid metabolism by peroxisomes and mitochondria, propionate and butyrate concentrations correlate inversely with risk of obesity, insulin resistance and NAFLD. In this horizon-scanning review, we have compiled available evidence on the effects of protein malnutrition on OCFA production, arising from loss in mitochondrial, peroxisomal and gut microbiota function, and its association with lipid accumulation in the liver. The methyl donor amino acid composition of dietary protein is an important contributor to liver function and lipid storage; the presence and abundance of dietary branched-chain amino acids can modulate the composition and metabolic activity of the gut microbiome and, on the other hand, can affect protective OCFA and SCFA production in the liver. In preclinical animal models fed with low-protein diets, specific amino acid supplementation can ameliorate fatty liver disease. The association between low dietary protein intake and fatty liver disease is underexplored and merits further investigation, particularly in vulnerable groups with dietary protein restriction in developing countries.

Background : Wildlife poses a significant burden for the complete eradication of bovine tuberculosis (bTB). In particular, wild boar ( Sus scrofa ) is one of the most important reservoirs of Mycobacterium bovis , the causal agent of bTB. Wild boar can display from mild TB lesions, usually found in head lymph nodes, to generalized TB lesions distributed in different anatomical regions; but rarely clinical signs, which complicates the diagnosis of Mycobacterium bovis infection and bTB control. Among the possibilities for this variability in lesion distribution is the influence of the host-beneficial commensal-primed immune barrier. In this respect, beneficial microbes may delay bTB dissemination as a consequence of an antagonistic competition for nutrients and phagocytes. In order to explore this possibility, we have tested whether typical commensals such as lactobacilli have the capacity to reduce the survival rate of the surrogate M. bovis strain Bacillus Calmette-Guerin (BCG); and to modulate its phagocyte intake. Results : Three Lactobacillus species, L. casei , L. plantarum, and L. salivarius , isolated from wild boar feces displayed a pH-dependent inhibitory activity against BCG and influenced its intake by porcine blood phagocytes in a species-dependent manner. All lactobacilli showed a very significant bactericidal effect against BCG at low pH, but only isolates of L. plantarum and L. casei displayed such antimycobacterial activity at neutral pH. The genomes of these isolates revealed the presence of two-peptide bacteriocins whose precursor genes up-regulate in the presence of BCG cells. Furthermore, L. plantarum reduced significantly the BCG phagocytic intake, whereas L. casei had the opposite effect. L. salivarius had no significant influence on the phagocytic response to BCG. Conclusions : Our in vitro results show that lactobacilli isolated from wild boar antagonize BCG as a consequence of their antimycobacterial activity and a competitive phagocytic response. These findings suggest that commensal bacteria could play a beneficial role in influencing the outcome of bTB dissemination. Further work with lactobacilli as a potential competitive pressure to control bTB will need to take into account the complex nature of the commensal microbiome, the specific immunity of the wild boar and the in vivo infection context with pathogenic strains of M. bovis .

BackgroundBovine tuberculosis (bTB) caused by Mycobacterium bovis is the most serious endemic disease affecting livestock in the UK. The European badger (Meles meles) is the most important wildlife reservoir of bTB transmission to cattle, making eradication particularly difficult. In this respect, oral vaccination with the attenuated M. bovis vaccine Bacillus Calmette-Guerin (BCG) has been suggested as a wide-scale intervention to reduce bTB infection in badgers. However, experimental studies show variable protection. Among the possibilities for this variation is that the resident gut bacteria may influence the success of oral vaccination in badgers; either through competitive exclusion and/or inhibition, or via effects on the host immune system. In order to explore this possibility, we have tested whether typical gut commensals such as Lactic Acid Bacteria (LAB) have the capacity to impact on the viability and survival rate of BCG and to modulate the immune response to BCG using an in vitro model.ResultsTwelve LAB isolated from badger faeces displayed inhibitory activity to BCG that was species-dependent. Weissella had a bacteriostatic effect, whereas isolates of enterococci, lactobacilli and pediococci had a more bactericidal activity. Furthermore, BCG-induced activation of the pro-inflammatory transcription factor NF-κB in human THP-1 macrophages was modulated by LAB in a strain-dependent manner. Most pediococci enhanced NF-κB activation but one strain had the opposite effect. Interestingly, isolates of enterococci, lactobacilli and weissella had different effects as immunomodulators of BCG-induced macrophage responses as some had no significant influence on NF-κB activation, but others increased it significantly.ConclusionsOur in vitro results show that LAB isolated from badgers exhibit significant inhibitory activity against BCG and influence the immune activation mediated by BCG in a human macrophage assay. These findings suggest that gut commensal bacteria could play a role in influencing the outcome of oral BCG vaccination. Inactivated cells of LAB, or LAB that are bacteriostatic but have a synergistic immunostimulatory effect with BCG, could be potential adjuvants to be used for oral vaccination in badgers. Further work is needed to take into account the complex nature of the gut microbiome, specific immunity of the badger and the in vivo context.Electronic supplementary materialThe online version of this article (10.1186/s12866-018-1210-z) contains supplementary material, which is available to authorized users.

Probiotics are noninvasive, environmentally friendly alternatives for reducing infectious diseases in wildlife species.Our aim in the present study was to evaluate the potential of gut commensals such as lactic acid bacteria (LAB) as wildlife probiotics. The LAB selected for our analyses were isolated from European badgers (Meles meles), a wildlife reservoir of bovine tuberculosis, and comprised four different genera: Enterococcus, Weissella, Pediococcus, and Lactobacillus. The enterococci displayed a phenotype and genotype that included the production of antibacterial peptides and stimulation of antiviral responses, as well as the presence of virulence and antibiotic resistance genes; Weissella showed antimycobacterial activity owing to their ability to produce lactate and ethanol; and lactobacilli and pediococci modulated proinflammatory phagocytic responses that associate with protection against pathogens, responses that coincide with the presence of immunomodulatory markers in their genomes. Although both lactobacilli and pediococci showed resistance to antibiotics, this was naturally acquired, and almost all isolates demonstrated a phylogenetic relationship with isolates from food and healthy animals. Our results show that LAB display probiotic benefits that depend on the genus, and that lactobacilli and pediococci are probably the most obvious candidates as probiotics against infectious diseases in wildlife because of their food-grade status and ability to modulate protective innate immune responses. . P. acidilactici E24, P. lolii F7, P. acidilactici I32, P. acidilactici M17, Weissella cibaria A23, W. paramesenteroides A37, and W. paramesenteroides N43. All displayed extracellular activity against Mycobacterium smegmatis at a low pH and reduced the viability and survival rate of M. bovis BCG when competing together in the same broth for 48 hours. 17 In the present study, further species analysis was carried out using the published Genbank genomes from E. faecalis, L. plantarum, L. reuterii, pediococci, and weissella with feature frequency profiling (FFP). 23 This technique allows both cross-species and cross-genus comparisons between genome sequences to confirm bacterial identification. The isolates previously identified as

The World Health Organization warns that the alarming increase in antibiotic resistant bacteria will lead to 2.7 million deaths annually due to the lack of effective antibiotic therapies. Clearly, there is an urgent need for short-term alternatives that help to alleviate these alarming figures. In this respect, the scientific community is exploring neglected ecological niches from which the prototypical antibiotic-producing bacteria Streptomycetes are expected to be present. Recent studies have reported that honeybees and their products carry Streptomyces species that possess strong antibacterial activity. In this study, we have investigated the antibiotic profile of two Streptomycetes strains that were isolated from beehives. One of the isolates is the strain Streptomyces albus AN1, which derives from pollen, and shows potent antimicrobial activity against Candida albicans. The other isolate is the strain Streptomyces griseoaurantiacus AD2, which was isolated from honey, and displays a broad range of antimicrobial activity against different Gram-positive bacteria, including pathogens such as Staphylococcus aureus and Enterococus faecalis. Cultures of S. griseoaurantiacus AD2 have the capacity to produce the antibacterial compounds undecylprodigiosin and manumycin, while those of S. albus AN1 accumulate antifungal compounds such as candicidins and antimycins. Furthermore, genome and dereplication analyses suggest that the number of putative bioactive metabolites produced by AD2 and AN1 is considerably high, including compounds with anti-microbial and anti-cancer properties. Our results postulate that beehives are a promising source for the discovery of novel bioactive compounds that might be of interest to the agri-food sector and healthcare pharmaceuticals.