#Lysocins: Bioengineered #Antimicrobials that Deliver #Lysins Across the Outer Membrane of Gram-Negative #Bacteria (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Lysocins: Bioengineered Antimicrobials that Deliver Lysins Across the Outer Membrane of Gram-Negative Bacteria

Ryan D. Heselpoth, Chad W. Euler, Raymond Schuch, Vincent A. Fischetti

DOI: 10.1128/AAC.00342-19

 

ABSTRACT

The prevalence of multidrug-resistant Pseudomonas aeruginosa has stimulated development of alternative therapeutics. Bacteriophage peptidoglycan hydrolases, termed lysins, represent an emerging antimicrobial option for targeting Gram-positive bacteria. However, lysins against Gram-negatives are generally deterred by the outer membrane and their inability to work in serum. One solution involves exploiting evolved delivery systems used by colicin-like bacteriocins (e.g., S-type pyocins of P. aeruginosa) to translocate through the outer membrane. Following surface receptor binding, colicin-like bacteriocins form Tol- or TonB-dependent translocons to actively import cytotoxic domains through outer membrane protein channels. With this understanding, we developed lysocins, which are bioengineered lysin-bacteriocinfusion molecules capable of periplasmic import. In our proof of concept studies, components from the P. aeruginosa bacteriocin pyocin S2 responsible for surface receptor binding and outer membrane translocation were fused to the GN4 lysin to generate the PyS2-GN4 lysocin. PyS2-GN4 delivered the GN4 lysin to the periplasm to induce peptidoglycan cleavage and log-fold P. aeruginosa death with minimal endotoxin release. While displaying narrow-spectrum antipseudomonal activity in human serum, PyS2-GN4 also efficiently disrupted biofilms, outperformed standard of care antibiotics, exhibited no cytotoxicity towards eukaryotic cells, and protected mice from P. aeruginosa challenge in a bacteremia model. In addition to P. aeruginosa, lysocins can be constructed to target other prominent Gram-negative bacterial pathogens.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Pseudomonas aeruginosa; Bacteriophages; Lysins; Bacteriocins; Lysocins.

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#Synergy between circular #bacteriocin AS-48 and #ethambutol against #Mycobacterium tuberculosis (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Synergy between circular bacteriocin AS-48 and ethambutol against Mycobacterium tuberculosis

Clara Aguilar-Pérez a,b#, Begoña Gracia a,b,c, Liliana Rodrigues a,b,c,d, Asunción Vitoria a,b,c,g, Rubén Cebrián e, Nathalie Deboosère f, Ok-ryul Song f, Priscille Brodin f, Mercedes Maqueda e and José A. Aínsa a,b,c#

Author Affiliations: a Departamento de Microbiología, Facultad de Medicina, and BIFI, Universidad de Zaragoza, Zaragoza, Spain; b Instituto de Investigación Sanitaria de Aragón (IIS-Aragón); {c} CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III; {d} Fundación Agencia Aragonesa para la Investigación y el Desarrollo (ARAID); {e} Departamento de Microbiología, Facultad de Ciencias, Universidad de Granada, Granada, Spain; f Université de Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 8204 – CIIL – Center for Infection and Immunity of Lille, Lille, France; g Grupo de Estudio de Infecciones por Micobacterias (GEIM) de la SEIMC, Madrid, Spain

 

ABSTRACT

The increasing incidence of multi-drug resistant Mycobacterium tuberculosis and the very few drugs available for treatment is promoting the discovery and development of new molecules that could help in the control of this disease. Bacteriocin AS-48 is an antibacterial peptide produced by Enterococcus faecalis, active against several Gram-positive bacteria. We have found that AS-48 was active against Mycobacterium tuberculosis, including H37Rv and other reference and clinical strains, and also against some non-tuberculous clinical mycobacterial species. The combination of AS-48 with either lysozyme or with ethambutol (commonly used in the treatment of drug susceptible tuberculosis) increased the antituberculosis action of AS-48, showing a synergic interaction. Under these conditions, AS-48 exhibits a MIC close to some of the first-line antituberculosis agents. The inhibitory activity of AS-48 and its synergistic combination with ethambutol was also observed on M. tuberculosis infected macrophages.

Finally, AS-48 did not show any cytotoxicity against THP-1, MHS and J774.2 macrophage cell lines, at concentrations close to its MIC. In summary, bacteriocin AS-48 has an interesting antimycobacterial activity in vitro and low cytotoxicity, so further studies in vivo will contribute to its development as a potential additional drug for antituberculosis therapy.

 

FOOTNOTES

#Corresponding authors: Clara Aguilar-Pérez, clara.a@unizar.es and José A. Aínsa, ainsa@unizar.es. Microbiology Department, University of Zaragoza, C/Domingo Miral s/n 50009-Zaragoza, Spain.

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Mycobacterium tuberculosis; Bacteriocins; Ethambutol.

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A novel #bacteriocin from #Enterococcus faecalis 478 exhibits a potent activity against #vancomycin-resistant enterococci (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

A novel bacteriocin from Enterococcus faecalis 478 exhibits a potent activity against vancomycin-resistant enterococci

Uraporn Phumisantiphong, Kanokrat Siripanichgon, Onrapak Reamtong, Pornphan Diraphat

Published: October 12, 2017 / DOI: https://doi.org/10.1371/journal.pone.0186415

 

Abstract

The emergence of multidrug-resistant enterococci (MDRE) and particularly vancomycin-resistant enterococci (VRE) is considered a serious health problem worldwide, causing the need for new antimicrobials. The aim of this study was to discover and characterize bacteriocin against clinical isolates of MDRE and VRE. Over 10,000 bacterial isolates from water, environment and clinical samples were screened. E. faecalis strain 478 isolated from human feces produced the highest antibacterial activity against several MDRE and VRE strains. The optimum condition for bacteriocin production was cultivation in MRS broth at 37°C, pH 5–6 for 16 hours. The bacteriocin-like substance produced from E. faecalis strain EF478 was stable at 60°C for at least 1 hour and retained its antimicrobial activity after storage at -20°C for 1 year, at 4°C for 6 months, and at 25°C for 2 months. A nano-HPLC electrospray ionization multi-stage tandem mass spectrometry (nLC-ESI-MS/MS) analysis showed that the amino acid sequences of the bacteriocin-like substance was similar to serine protease of E. faecalis, gi|488296663 (NCBI database), which has never been reported as a bacteriocin. This study reported a novel bacteriocin with high antibacterial activity against VRE and MDRE.

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Citation: Phumisantiphong U, Siripanichgon K, Reamtong O, Diraphat P (2017) A novel bacteriocin from Enterococcus faecalis 478 exhibits a potent activity against vancomycin-resistant enterococci. PLoS ONE12(10): e0186415. https://doi.org/10.1371/journal.pone.0186415

Editor: Daniela Flavia Hozbor, Universidad Nacional de la Plata, ARGENTINA

Received: February 22, 2017; Accepted: September 29, 2017; Published: October 12, 2017

Copyright: © 2017 Phumisantiphong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: The study was partially supported for publication by the China Medical Board (CMB), Faculty of Public Health, Mahidol University, Bangkok, Thailand. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Antibiotics; Drugs Resistance; Enterococci; Bacteriocins.

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#Bacteriocin #production: a relatively unharnessed #probiotic trait? (F1000 Res., abstract)

[Source: F1000 Research, full page: (LINK). Abstract, edited.]

REVIEW

Bacteriocin production: a relatively unharnessed probiotic trait? [version 1; referees: 2 approved]

James W. Hegarty1,2, Caitriona M. Guinane1, R. Paul Ross1,3, Colin Hill2,3, Paul D. Cotter1,3

Author affiliations: 1 Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland; 2 Department of Microbiology, University College Cork, Cork, Ireland; 3 APC Microbiome Institute, University College Cork, Cork, Ireland

Grant information: This work was funded by a Science Foundation Ireland award “Obesibiotics” (11/P1/1137) to PDC.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

 

Abstract

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. As such, the true potential of these antimicrobials has yet to be realised.

 

Corresponding author: Paul D. Cotter

How to cite: Hegarty JW, Guinane CM, Ross RP et al. Bacteriocin production: a relatively unharnessed probiotic trait? [version 1; referees: 2 approved]. F1000Research 2016, 5(F1000 Faculty Rev):2587 (doi: 10.12688/f1000research.9615.1)

Copyright: © 2016 Hegarty JW et al. This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Competing interests: The authors declare that they have no competing interests.

First published: 27 ott 2016, 5(F1000 Faculty Rev):2587 (doi: 10.12688/f1000research.9615.1)

Latest published: 27 ott 2016, 5(F1000 Faculty Rev):2587 (doi: 10.12688/f1000research.9615.1)

Keywords: Baceriocin.

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