The class-IIa HDAC inhibitor TMP269 promotes BMP-Smad signalling and is neuroprotective in in vitro and in vivo 6-hydroxydopamine models of Parkinson's disease.

Degeneration of midbrain nigrostriatal dopaminergic neurons is a pathological hallmark of Parkinson's disease (PD). Peripheral delivery of a compound(s) to arrest or slow this dopaminergic degeneration is a key therapeutic goal. Pan-inhibitors of histone deacetylase (HDAC) enzymes, key epigenetic regulators, have shown therapeutic promise in PD models.

A gut-derived produces the novel nisin variant designated nisin G and inhibits in a model of the human distal colon microbiome.

is a human pathogen associated with intestinal conditions including colorectal cancer. Screening for gut-derived strains that exhibit anti-. activity revealed DPC6487 as a strain of interest.

Inhibition of Clinical MRSA Isolates by Coagulase Negative Staphylococci of Human Origin.

is frequently highlighted as a priority for novel drug research due to its pathogenicity and ability to develop antibiotic resistance. Coagulase-negative staphylococci (CoNS) are resident flora of the skin and nares. Previous studies have confirmed their ability to kill and prevent colonization by through the production of bioactive substances.

Effect of a bacteriocin-producing on the pathogen in a model of the human distal colon.

The gut microbiome is a vast reservoir of microbes, some of which produce antimicrobial peptides called bacteriocins that may inhibit specific bacteria associated with disease. is an emerging human bacterial pathogen associated with gastrointestinal diseases including colorectal cancer (CRC). In this study, fecal samples of healthy donors were screened for potential bacteriocin-producing probiotics with antimicrobial activity against .

In Vitro and In Silico Based Approaches to Identify Potential Novel Bacteriocins from the Athlete Gut Microbiome of an Elite Athlete Cohort.

Exercise reduces inflammation, fatigue, and aids overall health. Additionally, physical fitness has been associated with desirable changes in the community composition of the athlete gut microbiome, with health-associated taxa being shown to be increased in active individuals. Here, using a combination of in silico and in vitro methods, we investigate the antimicrobial activity of the athlete gut microbiome.

The impact of the human microbiome in tumorigenesis, cancer progression, and biotherapeutic development.

Background: Cancer impacts millions of lives globally each year, with approximately 10 million cancer-related deaths recorded worldwide in 2020. Mounting research has recognised the human microbiome as a key area of interest in the pathophysiology of various human diseases including cancer tumorigenesis, progression and in disease outcome. It is suggested that approximately 20% of human cancers may be linked to microbes.

Generation of Nonpolar Deletion Mutants in Listeria monocytogenes Using the "SOEing" Method.

The ability to manipulate chromosomally encoded genes is a fundamental biological tool for the analysis of gene function. Here, we provide in greater depth a protocol for the creation of nonpolar unlabelled gene deletions in Listeria monocytogenes that are facilitated by the splicing overlap extension PCR technique. For mutagenesis in L.

Potential Use of Biotherapeutic Bacteria to Target Colorectal Cancer-Associated Taxa.

The role of the gut microbiome in human health and disease is the focus of much attention. It has been widely agreed upon that our gut bacteria play a role in host immunity, nutrient absorption, digestion, metabolism, and other key drivers of health. Furthermore, certain microbial signatures and specific taxa have also been associated with the development of diseases, such as obesity; inflammatory bowel disease; and, indeed, colorectal cancer (CRC), which is the focus of this review.

The Potential Impact of Probiotics on the Gut Microbiome of Athletes.

There is accumulating evidence that physical fitness influences the gut microbiome and as a result, promotes health. Indeed, exercise-induced alterations in the gut microbiome can influence health parameters crucial to athletic performance, specifically, immune function, lower susceptibility to infection, inflammatory response and tissue repair. Consequently, maintenance of a healthy gut microbiome is essential for an athlete's health, training and performance.

Bovine Staphylococcus aureus Superantigens Stimulate the Entire T Cell Repertoire of Cattle.

Superantigens (SAgs) represent a diverse family of bacterial toxins that induce Vβ-specific T cell proliferation associated with an array of important diseases in humans and animals, including mastitis of dairy cows. However, an understanding of the diversity and distribution of SAg genes among bovine strains and their role in the pathogenesis of mastitis is lacking. Population genomic analysis of 195 bovine isolates representing 57 unique sequence types revealed that strains encode 2 to 13 distinct SAgs and that the majority of isolates contain 5 or more SAg genes.

A Profile Hidden Markov Model to investigate the distribution and frequency of LanB-encoding lantibiotic modification genes in the human oral and gut microbiome.

Background: The human microbiota plays a key role in health and disease, and bacteriocins, which are small, bacterially produced, antimicrobial peptides, are likely to have an important function in the stability and dynamics of this community. Here we examined the density and distribution of the subclass I lantibiotic modification protein, LanB, in human oral and stool microbiome datasets using a specially constructed profile Hidden Markov Model (HMM).

Methods: The model was validated by correctly identifying known lanB genes in the genomes of known bacteriocin producers more effectively than other methods, while being sensitive enough to differentiate between different subclasses of lantibiotic modification proteins.

Genome Sequence of DPC5671, a Strain Isolated from Cheddar Cheese.

The draft genome sequence of DPC5671, isolated from cheddar cheese, was determined. is a common Gram-positive bacterium detected on the surface of smear-ripened cheese and other fermented foods.

Whey protein effects on energy balance link the intestinal mechanisms of energy absorption with adiposity and hypothalamic neuropeptide gene expression.

We tested the hypothesis that dietary whey protein isolate (WPI) affects the intestinal mechanisms related to energy absorption and that the resulting energy deficit is compensated by changes in energy balance to support growth. C57BL/6 mice were provided a diet enriched with WPI with varied sucrose content, and the impact on energy balance-related parameters was investigated. As part of a high-sucrose diet, WPI reduced the hypothalamic expression of pro-opiomelanocortin gene expression and increased energy intake.

Bacteriocin production: a relatively unharnessed probiotic trait?

Probiotics are "live microorganisms which, when consumed in adequate amounts, confer a health benefit to the host". A number of attributes are highly sought after among these microorganisms, including immunomodulation, epithelial barrier maintenance, competitive exclusion, production of short-chain fatty acids, and bile salt metabolism. Bacteriocin production is also generally regarded as a probiotic trait, but it can be argued that, in contrast to other traits, it is often considered a feature that is desirable, rather than a key probiotic trait.

The bacteriocin bactofencin A subtly modulates gut microbial populations.

The diverse and dynamic microbiota of the gastrointestinal tract represents a vast source of bioactive substances. These include bacteriocins, which are antimicrobial peptides with the potential to modulate gut populations to impact positively on human health. Although several gut-derived bacteriocins have been isolated, there remain only a few exceptional studies in which their influence on microbial populations within the gut has been investigated.

In silico identification of bacteriocin gene clusters in the gastrointestinal tract, based on the Human Microbiome Project's reference genome database.

Background: The human gut microbiota comprises approximately 100 trillion microbial cells which significantly impact many aspects of human physiology - including metabolism, nutrient absorption and immune function. Disturbances in this population have been implicated in many conditions and diseases, including obesity, type-2 diabetes and inflammatory bowel disease. This suggests that targeted manipulation or shaping of the gut microbiota, by bacteriocins and other antimicrobials, has potential as a therapeutic tool for the prevention or treatment of these conditions.

Impact of Environmental Factors on Bacteriocin Promoter Activity in Gut-Derived Lactobacillus salivarius.

Bacteriocin production is regarded as a desirable probiotic trait that aids in colonization and persistence in the gastrointestinal tract (GIT). Strains of Lactobacillus salivarius, a species associated with the GIT, are regarded as promising probiotic candidates and have a number of associated bacteriocins documented to date. These include multiple class IIb bacteriocins (salivaricin T, salivaricin P, and ABP-118) and the class IId bacteriocin bactofencin A, which show activity against medically important pathogens.

Nisin H Is a New Nisin Variant Produced by the Gut-Derived Strain Streptococcus hyointestinalis DPC6484.

Accumulating evidence suggests that bacteriocin production represents a probiotic trait for intestinal strains to promote dominance, fight infection, and even signal the immune system. In this respect, in a previous study, we isolated from the porcine intestine a strain of Streptococcus hyointestinalis DPC6484 that displays antimicrobial activity against a wide range of Gram-positive bacteria and produces a bacteriocin with a mass of 3,453 Da. Interestingly, the strain was also found to be immune to a nisin-producing strain.

A single natural nucleotide mutation alters bacterial pathogen host tropism.

The capacity of microbial pathogens to alter their host tropism leading to epidemics in distinct host species populations is a global public and veterinary health concern. To investigate the molecular basis of a bacterial host-switching event in a tractable host species, we traced the evolutionary trajectory of the common rabbit clone of Staphylococcus aureus. We report that it evolved through a likely human-to-rabbit host jump over 40 years ago and that only a single naturally occurring nucleotide mutation was required and sufficient to convert a human-specific S.

Genome Sequence of the Heteropolysaccharide-Producing Strain Lactobacillus mucosae DPC 6426.

Exopolysaccharide-synthesizing Lactobacillus mucosae DPC 6426 is a heterofermentative strain, which has demonstrated cholesterol-lowering properties in an animal model of lipid-driven atherosclerosis. The genome revealed a plethora of homologues linked to carbohydrate metabolism and mucin binding.

Genome analysis of Cronobacter phage vB_CsaP_Ss1 reveals an endolysin with potential for biocontrol of Gram-negative bacterial pathogens.

Bacteriophages and their derivatives are continuously gaining impetus as viable alternative therapeutic agents to control harmful multidrug-resistant bacterial pathogens, particularly in the food industry. The reduced efficacy of conventional antibiotics has resulted in a quest to find novel alternatives in the war against infectious disease. This study describes the full-genome sequence of Cronobacter phage vB_CsaP_Ss1, with subsequent cloning and expression of its endolysin, capable of hydrolysing Gram-negative peptidoglycan.

Generation of nonpolar deletion mutants in Listeria monocytogenes using the "SOEing" method.

The ability to manipulate chromosomally encoded genes is a fundamental biological tool for the analysis of gene function. Here, we provide in greater depth protocols for the creation of nonpolar unlabeled gene deletions in Listeria (L.) monocytogenes that are facilitated by the splicing overlap extension PCR technique.