• Actinomyces Produces Defensin-Like Bacteriocins (Actifensins) with a Highly Degenerate Structure and Broad Antimicrobial Activity

      Sugrue, Ivan; O’Connor, Paula M.; Hill, Colin; Stanton, Catherine; Ross, R. Paul; Teagasc Walsh Fellowship Programme; JPI; Science Foundation Ireland; SFI/12/RC/2273 (American Society for Microbiology, 2020-01-29)
      We identified a strain of Actinomyces ruminicola which produces a potent bacteriocin with activity against a broad range of Gram-positive bacteria, many of which are pathogenic to animals and humans. The bacteriocin was purified and found to have a mass of 4,091 ± 1 Da with a sequence of GFGCNLITSNPYQCSNHCKSVGYRGGYCKLRTVCTCY containing three disulfide bridges. Surprisingly, near relatives of actifensin were found to be a series of related eukaryotic defensins displaying greater than 50% identity to the bacteriocin. A pangenomic screen further revealed that production of actifensin-related bacteriocins is a common trait within the genus, with 47 being encoded in 161 genomes. Furthermore, these bacteriocins displayed a remarkable level of diversity with a mean amino acid identity of only 52% between strains/species. This level of redundancy suggests that this new class of bacteriocins may provide a very broad structural basis on which to deliver and design new broad-spectrum antimicrobials for treatment of animal and human infections. IMPORTANCE Bacteriocins (ribosomally produced antimicrobial peptides) are potential alternatives to current antimicrobials given the global challenge of antimicrobial resistance. We identified a novel bacteriocin from Actinomyces ruminicola with no previously characterized antimicrobial activity. Using publicly available genomic data, we found a highly conserved yet divergent family of previously unidentified homologous peptide sequences within the genus Actinomyces with striking similarity to eukaryotic defensins. These actifensins may provide a potent line of antimicrobial defense/offense, and the machinery to produce them could be used for the design of new antimicrobials given the degeneracy that exists naturally in their structure.
    • Assessing the ability of Nisin A and derivatives thereof to inhibit Gram-negative bacteria from the genus Thermus

      Jonnala, Bhagya R. Yeluri; Feehily, Conor; O'Connor, Paula M.; Field, Des; Hill, Colin; Ross, R. Paul; McSweeney, P. L. H.; Sheehan, Diarmuid (JJ); Cotter, Paul D. (2020-12-09)
    • Comparative Genomics Analysis of Lactobacillus ruminis from Different Niches

      Wang, Shuo; Yang, Bo; Ross, R. Paul; STANTON, CATHERINE; Zhao, Jianxin; Zhang, Hao; Chen, Wei; National Natural Science Foundation of China; Jiangsu Province; 31771953; et al. (MDPI AG, 2020-01-08)
      Lactobacillus ruminis is a commensal motile lactic acid bacterium living in the intestinal tract of humans and animals. Although a few genomes of L. ruminis were published, most of them were animal derived. To explore the genetic diversity and potential niche-specific adaptation changes of L. ruminis, in the current work, draft genomes of 81 L. ruminis strains isolated from human, bovine, piglet, and other animals were sequenced, and comparative genomic analysis was performed. The genome size and GC content of L. ruminis on average were 2.16 Mb and 43.65%, respectively. Both the origin and the sampling distance of these strains had a great influence on the phylogenetic relationship. For carbohydrate utilization, the human-derived L. ruminis strains had a higher consistency in the utilization of carbon source compared to the animal-derived strains. L. ruminis mainly increased the competitiveness of niches by producing class II bacteriocins. The type of clustered regularly interspaced short palindromic repeats /CRISPR-associated (CRISPR/Cas) system presented in L. ruminis was mainly subtype IIA. The diversity of CRISPR/Cas locus depended on the high denaturation of spacer number and sequence, although cas1 protein was relatively conservative. The genetic differences in those newly sequenced L. ruminis strains highlighted the gene gains and losses attributed to niche adaptations.
    • Core fecal microbiota of domesticated herbivorous ruminant, hindgut fermenters, and monogastric animals

      O’ Donnell, Michelle M.; Harris, Hugh M. B.; Ross, R. Paul; O'Toole, Paul W.; Science Foundation Ireland; 07/ IN.1/B1780 (Wiley, 2017-08-22)
      In this pilot study, we determined the core fecal microbiota composition and overall microbiota diversity of domesticated herbivorous animals of three digestion types: hindgut fermenters, ruminants, and monogastrics. The 42 animals representing 10 animal species were housed on a single farm in Ireland and all the large herbivores consumed similar feed, harmonizing two of the environmental factors that influence the microbiota. Similar to other mammals, the fecal microbiota of all these animals was dominated by the Firmicutes and Bacteroidetes phyla. The fecal microbiota spanning all digestion types comprised 42% of the genera identified. Host phylogeny and, to a lesser extent, digestion type determined the microbiota diversity in these domesticated herbivores. This pilot study forms a platform for future studies into the microbiota of nonbovine and nonequine domesticated herbivorous animals.
    • Diversity of Gut Microbiota and Bifidobacterial Community of Chinese Subjects of Different Ages and from Different Regions

      Yang, Bo; Yan, Shuang; Chen, Yang; Ross, R. Paul; STANTON, CATHERINE; Zhao, Jianxin; Zhang, Hao; Chen, Wei; National Natural Science Foundation of China; National First-Class Discipline Program of Food Science and Technology; et al. (MDPI AG, 2020-07-24)
      Gut microbiota composition and functionality are closely linked to host health. In this study, the fecal microbiota and bifidobacterial communities of 111 healthy volunteers from four regions of China of varying age profiles (Child, 1–5 years; Young, 18–50 years; Elder, 60–80 years; Longevity, ≥90 years) were investigated via high-throughput sequencing. Canonical analysis revealed that the gut microbiota, as well as bifidobacteria profiles of the subjects, clustered according to their regions and age. Eight genera were shared among all subjects, however, certain genera distributed differently in subjects grouped by region and age. Faecalibacterium was enriched in samples from Zhongxiang, unclassified Ruminococcaceae and Christensenellaceae were enriched in the Longevity group, and Bifidobacterium was enriched in Child. Within Bifidobacterium, B. longum was the most abundant species in almost all samples except for Child, in which B. pseudocatenulatum was the most abundant. Additionally, the abundances of B. adolescentis and B. dentium were lower in Child. In conclusion, our results suggest that geography and age affect the structure of the gut microbiota, as well as Bifidobacterium composition, and this variation may greatly associate with the metabolic and immune changes that occur during the process of aging.
    • Evaluation of Phage Therapy in the Context of Enterococcus faecalis and Its Associated Diseases

      Bolocan, Andrei S.; Upadrasta, Aditya; de Almeida Bettio, Pedro H.; Clooney, Adam G.; Draper, Lorraine A.; Ross, R. Paul; Hill, Colin; Science Foundation Ireland; European Union; Janssen Biotech, Inc.; et al. (MDPI, 2019-04-20)
      Bacteriophages (phages) or bacterial viruses have been proposed as natural antimicrobial agents to fight against antibiotic-resistant bacteria associated with human infections. Enterococcus faecalis is a gut commensal, which is occasionally found in the mouth and vaginal tract, and does not usually cause clinical problems. However, it can spread to other areas of the body and cause life-threatening infections, such as septicemia, endocarditis, or meningitis, in immunocompromised hosts. Although E. faecalis phage cocktails are not commercially available within the EU or USA, there is an accumulated evidence from in vitro and in vivo studies that have shown phage efficacy, which supports the idea of applying phage therapy to overcome infections associated with E. faecalis. In this review, we discuss the potency of bacteriophages in controlling E. faecalis, in both in vitro and in vivo scenarios. E. faecalis associated bacteriophages were compared at the genome level and an attempt was made to categorize phages with respect to their suitability for therapeutic application, using orthocluster analysis. In addition, E. faecalis phages have been examined for the presence of antibiotic-resistant genes, to ensure their safe use in clinical conditions. Finally, the domain architecture of E. faecalis phage-encoded endolysins are discussed.
    • Gut microbes from the phylogenetically diverse genus Eubacterium and their various contributions to gut health

      Mukherjee, Arghya; Lordan, Cathy; Ross, R. Paul; Cotter, Paul D.; Department of Agriculture, Food and the Marine; Teagasc Walsh Fellowship; Science Foundation Ireland; EU; 15/F/635; 2017047; et al. (Taylor & Francis, 2020-08-23)
      Over the last two decades our understanding of the gut microbiota and its contribution to health and disease has been transformed. Among a new ‘generation’ of potentially beneficial microbes to have been recognized are members of the genus Eubacterium, who form a part of the core human gut microbiome. The genus consists of phylogenetically, and quite frequently phenotypically, diverse species, making Eubacterium a taxonomically unique and challenging genus. Several members of the genus produce butyrate, which plays a critical role in energy homeostasis, colonic motility, immunomodulation and suppression of inflammation in the gut. Eubacterium spp. also carry out bile acid and cholesterol transformations in the gut, thereby contributing to their homeostasis. Gut dysbiosis and a consequently modified representation of Eubacterium spp. in the gut, have been linked with various human disease states. This review provides an overview of Eubacterium species from a phylogenetic perspective, describes how they alter with diet and age and summarizes its association with the human gut and various health conditions.
    • Influence of pasture feeding on milk and meat products in terms of human health and product quality

      STANTON, CATHERINE; Mills, S.; Ryan, A.; Di Gioia, D.; Ross, R. Paul (Teagasc, 2021-02-02)
      Cows are fed either indoors on a diet of mixed ration or in areas with temperate climates, such as Ireland and New Zealand, the feeding regime of dairy and beef herds is almost entirely pasture-based. Animal feeding regimes and herd management practices are linked to differences in organoleptic and nutritional quality attributes of milk, dairy and meat/beef products, with pasture-based feeding systems being associated with superior quality produce. Consumers generally perceive that milk and meat products produced from outdoor grazing pastures are “healthier” than produce derived from indoor feeding systems, based on animals fed typical indoor rations and concentrates. However, while research has demonstrated differences in milk and meat quality, especially in terms of fatty acids, based on different feeding systems, data are limited on the impact of dairy and meat products produced from different feeding systems on human health.