Re-sensitizing Ampicillin and Kanamycin-Resistant E. coli and S. aureus Using Synergistic Metal Micronutrients-Antibiotic Combinations
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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media
2020
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| Online Access: | http://eprints.uanl.mx/23304/1/23304.pdf |
| _version_ | 1824416832699760640 |
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| author | Garza Cervantes, Javier Alberto Meza Bustillos, Jesús F. Reséndiz Hernández, Haziel Suárez Cantú, Iván A. Ortega Rivera, Oscar Antonio Salinas, Eva Escárcega González, Carlos Enrique Morones Ramírez, José Rubén |
| author_facet | Garza Cervantes, Javier Alberto Meza Bustillos, Jesús F. Reséndiz Hernández, Haziel Suárez Cantú, Iván A. Ortega Rivera, Oscar Antonio Salinas, Eva Escárcega González, Carlos Enrique Morones Ramírez, José Rubén |
| author_sort | Garza Cervantes, Javier Alberto |
| collection | Repositorio Institucional |
| description | 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, Cu2+, Zn2+, Co2+, Cd2+, and Ni2+ 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 Cu2+, Cd2+, or Ni2. Similarly, Cu2+, Zn2+, or Cd2+ 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. |
| format | Article |
| id | eprints-23304 |
| institution | UANL |
| language | English |
| publishDate | 2020 |
| publisher | Frontiers Media |
| record_format | eprints |
| spelling | eprints-233042022-05-29T12:27:59Z http://eprints.uanl.mx/23304/ Re-sensitizing Ampicillin and Kanamycin-Resistant E. coli and S. aureus Using Synergistic Metal Micronutrients-Antibiotic Combinations Garza Cervantes, Javier Alberto Meza Bustillos, Jesús F. Reséndiz Hernández, Haziel Suárez Cantú, Iván A. Ortega Rivera, Oscar Antonio Salinas, Eva Escárcega González, Carlos Enrique Morones Ramírez, José Rubén QR Microbiología 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, Cu2+, Zn2+, Co2+, Cd2+, and Ni2+ 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 Cu2+, Cd2+, or Ni2. Similarly, Cu2+, Zn2+, or Cd2+ 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. Frontiers Media 2020 Article PeerReviewed text en cc_by_nc_nd http://eprints.uanl.mx/23304/1/23304.pdf http://eprints.uanl.mx/23304/1.haspreviewThumbnailVersion/23304.pdf Garza Cervantes, Javier Alberto y Meza Bustillos, Jesús F. y Reséndiz Hernández, Haziel y Suárez Cantú, Iván A. y Ortega Rivera, Oscar Antonio y Salinas, Eva y Escárcega González, Carlos Enrique y Morones Ramírez, José Rubén (2020) Re-sensitizing Ampicillin and Kanamycin-Resistant E. coli and S. aureus Using Synergistic Metal Micronutrients-Antibiotic Combinations. Frontiers in Bioengineering and Biotechnology, 8. pp. 1-21. ISSN 2296-4185 http://doi.org/10.3389/fbioe.2020.00612 doi:10.3389/fbioe.2020.00612 |
| spellingShingle | QR Microbiología Garza Cervantes, Javier Alberto Meza Bustillos, Jesús F. Reséndiz Hernández, Haziel Suárez Cantú, Iván A. Ortega Rivera, Oscar Antonio Salinas, Eva Escárcega González, Carlos Enrique Morones Ramírez, José Rubén Re-sensitizing Ampicillin and Kanamycin-Resistant E. coli and S. aureus Using Synergistic Metal Micronutrients-Antibiotic Combinations |
| thumbnail | https://rediab.uanl.mx/themes/sandal5/images/online.png |
| title | Re-sensitizing Ampicillin and Kanamycin-Resistant E. coli and S. aureus Using Synergistic Metal Micronutrients-Antibiotic Combinations |
| title_full | Re-sensitizing Ampicillin and Kanamycin-Resistant E. coli and S. aureus Using Synergistic Metal Micronutrients-Antibiotic Combinations |
| title_fullStr | Re-sensitizing Ampicillin and Kanamycin-Resistant E. coli and S. aureus Using Synergistic Metal Micronutrients-Antibiotic Combinations |
| title_full_unstemmed | Re-sensitizing Ampicillin and Kanamycin-Resistant E. coli and S. aureus Using Synergistic Metal Micronutrients-Antibiotic Combinations |
| title_short | Re-sensitizing Ampicillin and Kanamycin-Resistant E. coli and S. aureus Using Synergistic Metal Micronutrients-Antibiotic Combinations |
| title_sort | re sensitizing ampicillin and kanamycin resistant e coli and s aureus using synergistic metal micronutrients antibiotic combinations |
| topic | QR Microbiología |
| url | http://eprints.uanl.mx/23304/1/23304.pdf |
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