• Bacteriocin-Antimicrobial Synergy: A Medical and Food Perspective

      Mathur, Harsh; Field, Des; Rea, Mary; Cotter, Paul D.; Hill, Colin; Ross, R Paul; Science Foundation Ireland; SFI/12/RC/2273 (Frontiers, 29/06/2017)
      The continuing emergence of multi-drug resistant pathogens has sparked an interest in seeking alternative therapeutic options. Antimicrobial combinatorial therapy is one such avenue. A number of studies have been conducted, involving combinations of bacteriocins with other antimicrobials, to circumvent the development of antimicrobial resistance and/or increase antimicrobial potency. Such bacteriocin-antimicrobial combinations could have tremendous value, in terms of reducing the likelihood of resistance development due to the involvement of two distinct mechanisms of antimicrobial action. Furthermore, antimicrobial synergistic interactions may also have potential financial implications in terms of decreasing the costs of treatment by reducing the concentration of an expensive antimicrobial and utilizing it in combination with an inexpensive one. In addition, combinatorial therapies with bacteriocins can broaden antimicrobial spectra and/or result in a reduction in the concentration of an antibiotic required for effective treatments to the extent that potentially toxic or adverse side effects can be reduced or eliminated. Here, we review studies in which bacteriocins were found to be effective in combination with other antimicrobials, with a view to targeting clinical and/or food-borne pathogens. Furthermore, we discuss some of the bottlenecks which are currently hindering the development of bacteriocins as viable therapeutic options, as well as addressing the need to exercise caution when attempting to predict clinical outcomes of bacteriocin-antimicrobial combinations.
    • 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.
    • Reincarnation of Bacteriocins From the Lactobacillus Pangenomic Graveyard

      Collins, Fergus W. J.; Mesa-Pereira, Beatriz; O'Connor, Paula M.; Rea, Mary; Hill, Colin; Ross, R Paul; Science Foundation Ireland; SFI/12/RC/227 (Frontiers, 02/07/2018)
      Bacteria commonly produce narrow spectrum bacteriocins as a means of inhibiting closely related species competing for similar resources in an environment. The increasing availability of genomic data means that it is becoming easier to identify bacteriocins encoded within genomes. Often, however, the presence of bacteriocin genes in a strain does not always translate into biological antimicrobial activity. For example, when analysing the Lactobacillus pangenome we identified strains encoding ten pediocin-like bacteriocin structural genes which failed to display inhibitory activity. Nine of these bacteriocins were novel whilst one was identified as the previously characterized bacteriocin “penocin A.” The composition of these bacteriocin operons varied between strains, often with key components missing which are required for bacteriocin production, such as dedicated bacteriocin transporters and accessory proteins. In an effort to functionally express these bacteriocins, the structural genes for the ten pediocin homologs were cloned alongside the dedicated pediocin PA-1 transporter in both Escherichia coli and Lactobacillus paracasei heterologous hosts. Each bacteriocin was cloned with its native leader sequence and as a fusion protein with the pediocin PA-1 leader sequence. Several of these bacteriocins displayed a broader spectrum of inhibition than the original pediocin PA-1. We show how potentially valuable bacteriocins can easily be “reincarnated” from in silico data and produced in vitro despite often lacking the necessary accompanying machinery. Moreover, the study demonstrates how genomic datasets such as the Lactobacilus pangenome harbor a potential “arsenal” of antimicrobial activity with the possibility of being activated when expressed in more genetically amenable hosts.
    • Reincarnation of Bacteriocins From the Lactobacillus Pangenomic Graveyard

      Collins, Fergus W. J.; Mesa-Pereira, Beatriz; O'Connor, Paula M.; Rea, Mary; Hill, Colin; Ross, R Paul; Science Foundation Ireland; SFI/12/RC/227 (Frontiers, 2018-07-02)
      Bacteria commonly produce narrow spectrum bacteriocins as a means of inhibiting closely related species competing for similar resources in an environment. The increasing availability of genomic data means that it is becoming easier to identify bacteriocins encoded within genomes. Often, however, the presence of bacteriocin genes in a strain does not always translate into biological antimicrobial activity. For example, when analysing the Lactobacillus pangenome we identified strains encoding ten pediocin-like bacteriocin structural genes which failed to display inhibitory activity. Nine of these bacteriocins were novel whilst one was identified as the previously characterized bacteriocin “penocin A.” The composition of these bacteriocin operons varied between strains, often with key components missing which are required for bacteriocin production, such as dedicated bacteriocin transporters and accessory proteins. In an effort to functionally express these bacteriocins, the structural genes for the ten pediocin homologs were cloned alongside the dedicated pediocin PA-1 transporter in both Escherichia coli and Lactobacillus paracasei heterologous hosts. Each bacteriocin was cloned with its native leader sequence and as a fusion protein with the pediocin PA-1 leader sequence. Several of these bacteriocins displayed a broader spectrum of inhibition than the original pediocin PA-1. We show how potentially valuable bacteriocins can easily be “reincarnated” from in silico data and produced in vitro despite often lacking the necessary accompanying machinery. Moreover, the study demonstrates how genomic datasets such as the Lactobacilus pangenome harbor a potential “arsenal” of antimicrobial activity with the possibility of being activated when expressed in more genetically amenable hosts.