#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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Giuseppe Michieli

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.