Potential of bacteriocin producing bacteria to control VRE infection

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Wiggins Savage, Kelsie
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University College Cork
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Antimicrobial resistance has been a growing and concerning problem over the last decade. It is estimated that antibiotic resistant pathogens cause up to 700,000 deaths each year. The Centre for Disease Control ranks vancomycin resistant enterococci as a serious threat. They estimate that in 2017 alone there were at least 54,500 cases in hospitalized patients. The rise of antibiotic resistance globally has led to a pressing need to develop therapeutic alternatives. Bacteriocins, small ribosomally synthesised peptides, have been proposed as one such alternative. Bacteriocins are non-toxic to producer strains and have been shown to exhibit antimicrobial ability against multi-drug resistant species including VRE and MRSA. This makes them excellent candidates as a substitute to antibiotics. In Chapter 1 the mechanism behind vancomycin resistance in Enterococcus faecium and Enterococcus faecalis is discussed. Also discussed are the chemotherapeutic treatments currently in use in treatment of VRE infections. Finally, a number of novel alternatives to antibiotics such as bacteriocins and bacteriophage and their efficiency are evaluated. In Chapter 2, the ability of Avicin, a Class II bacteriocin to inhibit growth of vancomycin resistant enterococci is investigated. Avicin was found to inhibit all six VRE strains in this experiment. One of these strains is a multi-drug resistant E. faecium APC1031 which is highly resistant to vancomycin (MIC 62μg/mL). MIC (Minimum inhibitory concentration the lowest concentration of an antibiotic that will prevent visible growth of bacteria. E. faecium APC1031 is sensitive to Avicin (MIC 0.9μg/mL). It was found that Avicin initially has a dramatic impact on cfu/mL of an established culture of APC1031. Addition of concentrations as low as 2μg/mL to a culture resulted in a 9 log decrease in cfu/mL after a two hour period but a number of cells did survive. The phenotype of these cells was assessed, and they exhibited a high level of resistance to Avicin (MIC 45-90μg/mL). More importantly these colonies exhibited decreased resistance to vancomycin (from 62μg/mL to 0.9μg/mL). This phenotypic change post-treatment with Avicin remained consistent when varying concentrations of Avicin were used. A combination of both Avicin and vancomycin resulted in an 8 log reduction of cfu of 108 cfu/mL to less than 3 cells surviving after 48 hours of incubation. Finally, whole genome sequencing of the Avicin resistant “mutants” revealed SNP’s in both the vanR region and the manZ region. VanR is a part of the two component regulatory system (vanS-vanR) which confers resistance to the glycopeptide, vancomycin. The results in this thesis highlight the potential of Avicin to be used in a combination with vancomycin for the treatment of VRE infections – VRE are killed by Avicin and where Avicin resistance occurs the resulting cells would revert to vancomycin sensitivity and consequently be killed by vancomycin.
Bacteriocins , VRE , Vancomycin , Enterococcus , Antibiotics
Wiggins Savage, K. 2021. Potential of bacteriocin producing bacteria to control VRE infection. MSc Thesis, University College Cork.