Malt isolate Lactobacillus sakei 5 produces three bacteriocins, sakacin P, sakacin T and sakacin X. The structural and regulatory genes for sakacin T and sakacin X are part of the sakacin TX locus, which consists of two adjacent, but divergently oriented gene clusters. Primer extension transcriptional analysis pointed to the existence of three distinct promoters within the sakacin TX locus, indicating that the three-component regulatory system in this locus is atypical in the sense that it is divided into a pheromone-specifying operon and an operon containing the genes for the histidine protein kinase and response regulator. Quantitative real-time PCR analyses showed that a transient increase in the expression of these two regulatory operons precedes transcription of the bacteriocin genes and appearance of bacteriocins in the culture medium. The identified promoters of the sakacin TX locus contain putative regulatory sequences (direct repeats) at corresponding positions in front of their -10 regions, which are likely to play a role in gene regulation.
"TB is too often a death sentence. It does not have to be this way,"- Nelson Mandela. Despite the success of anti-mycobacterial drugs over the past 70 years, mycobacterial disease, particularly tuberculosis is still responsible for millions of annual deaths worldwide. Additionally, the emergence of Multidrug Resistant (MDR-TB) and Extensively Drug Resistant (XDR-TB) Tuberculosis has motivated calls by the World Health Organization (WHO) for novel drugs, vaccines and diagnostic tests. Consequently, the identification and evaluation of a range of anti-mycobacterial compounds against pathogenic mycobacterial species is of paramount importance. My colleagues and I at Cork Institute of Technology (CIT) and University College Cork (UCC) have tackled this issue through the initial optimization of the rapid, robust and inexpensive microtitre alamarBlue assay (MABA) and subsequent employment of this assay to facilitate the rapid assessment of a new wave of potential therapeutic compounds, namely bacteriocins, in particular type 1 bacteriocins known as lantibiotics. The gene encoded nature of these peptides facilitates their genetic manipulation and consequent activities as anti-microbial agents. In this regard, it may be possible to one day develop diverse populations of anti-mycobacterial bacteriocins with species specific activities. This may in turn provide more targeted therapies, resulting in less side effects, shorter treatment times and thus better patient compliance. Although current drug regimes are effective in the interim, previous lessons have taught us not to be complacent. In the words of the Intel founder Andrew Grove, 'Success breeds complacency. Complacency breeds failure. Only the paranoid survive'. Armed with knowledge of previous failures, it is the duty of the scientific community to anticipate future bacterial resistance and have an arsenal of compounds standing by in such an eventuality.
Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne’s disease in ruminants, a chronic enteritis which results in emaciation and eventual loss of the animal. Recent advances in metagenomics have allowed a more in-depth study of complex microbiomes, including that of gastrointestinal tracts, and have the potential to provide insights into consequences of the exposure of an animal to MAP or other pathogens. This study aimed to investigate taxonomic diversity and compositional changes of the faecal microbiome of cattle experimentally challenged with MAP compared to an unexposed control group. Faecal swab samples were collected from a total of 55 animals [exposed group (n = 35) and a control group (n = 20)], across three time points (months 3, 6 and 9 post-inoculation). The composition and functional potential of the faecal microbiota differed across time and between the groups (p < 0.05), with the primary differences, from both a taxonomic and functional perspective, occurring at 3 months post inoculation. These included significant differences in the relative abundance of the genera Methanobrevibacter and Bifidobacterium and also of 11 other species (4 at a higher relative abundance in the exposed group and 7 at a higher relative abundance in the control group). Correlations were made between microbiome data and immunopathology measurements and it was noted that changes in the microbial composition correlated with miRNA-155, miR-146b and IFN-ɣ. In summary, this study illustrates the impact of exposure to MAP on the ruminant faecal microbiome with a number of species that may have relevance in veterinary medicine for tracking exposure to MAP.
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