Re-sensitizing Ampicillin and Kanamycin-Resistant E. coli and S. aureus Using Synergistic Metal Micronutrients-Antibiotic Combinations.

Autor:	Garza-Cervantes JA; Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, UANL, San Nicolás de los Garza, Mexico.; Centro de Investigación en Biotecnologíay Nanotecnología, Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Apodaca, Mexico., Meza-Bustillos JF; Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, UANL, San Nicolás de los Garza, Mexico., Resendiz-Hernández H; Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, UANL, San Nicolás de los Garza, Mexico., Suárez-Cantú IA; Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, UANL, San Nicolás de los Garza, Mexico., Ortega-Rivera OA; Departamento de Microbiología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, Mexico., Salinas E; Departamento de Microbiología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, Mexico., Escárcega-González CE; Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, UANL, San Nicolás de los Garza, Mexico.; Centro de Investigación en Biotecnologíay Nanotecnología, Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Apodaca, Mexico., Morones-Ramírez JR; Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, UANL, San Nicolás de los Garza, Mexico.; Centro de Investigación en Biotecnologíay Nanotecnología, Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Apodaca, Mexico.
Jazyk:	angličtina
Zdroj:	Frontiers in bioengineering and biotechnology [Front Bioeng Biotechnol] 2020 Jun 24; Vol. 8, pp. 612. Date of Electronic Publication: 2020 Jun 24 (Print Publication: 2020).
DOI:	10.3389/fbioe.2020.00612
Abstrakt:	Due to the recent emergence of multi-drug resistant strains, the development of novel antimicrobial agents has become a critical issue. The use of micronutrient transition metals is a promising approach to overcome this problem since these compounds exhibit significant toxicity at low concentrations in prokaryotic cells. In this work, we demonstrate that at concentrations lower than their minimal inhibitory concentrations and in combination with different antibiotics, it is possible to mitigate the barriers to employ metallic micronutrients as therapeutic agents. Here, we show that when administered as a combinatorial treatment, Cu 2+ , Zn 2+ , Co 2+ , Cd 2+ , and Ni 2+ increase susceptibility of Escherichia coli and Staphylococcus aureus to ampicillin and kanamycin. Furthermore, ampicillin-resistant E. coli is re-sensitized to ampicillin when the ampicillin is administered in combination with Cu 2+ , Cd 2+ , or Ni 2 . Similarly, Cu 2+ , Zn 2+ , or Cd 2+ re-sensitize kanamycin-resistant E. coli and S. aureus to kanamycin when administered in a combinatorial treatment with those transition metals. Here, we demonstrate that for both susceptible and resistant bacteria, transition-metal micronutrients, and antibiotics interact synergistically in combinatorial treatments and exhibit increased effects when compared to the treatment with the antibiotic alone. Moreover, in vitro and in vivo assays, using a murine topical infection model, showed no toxicological effects of either treatment at the administered concentrations. Lastly, we show that combinatorial treatments can clear a murine topical infection caused by an antibiotic-resistant strain. Altogether, these results suggest that antibiotic-metallic micronutrient combinatorial treatments will play an important role in future developments of antimicrobial agents and treatments against infections caused by both susceptible and resistant strains. (Copyright © 2020 Garza-Cervantes, Meza-Bustillos, Resendiz-Hernández, Suárez-Cantú, Ortega-Rivera, Salinas, Escárcega-González and Morones-Ramírez.)
Databáze:	MEDLINE
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