Mycobacterial Aminoglycoside Acetyltransferases: A Little of Drug Resistance, and a Lot of Other Roles
Aminoglycoside acetyltransferases are important determinants of resistance to aminoglycoside antibiotics in most bacterial genera. In mycobacteria, however, aminoglycoside acetyltransferases contribute only partially to aminoglycoside susceptibility since they are related with low level resistance t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-01-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.00046/full |
| _version_ | 1819169562986283008 |
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| author | Fernando Sanz-García Ernesto Anoz-Carbonell Ernesto Anoz-Carbonell Esther Pérez-Herrán Carlos Martín Carlos Martín Ainhoa Lucía Ainhoa Lucía Liliana Rodrigues Liliana Rodrigues Liliana Rodrigues José A. Aínsa José A. Aínsa |
| author_facet | Fernando Sanz-García Ernesto Anoz-Carbonell Ernesto Anoz-Carbonell Esther Pérez-Herrán Carlos Martín Carlos Martín Ainhoa Lucía Ainhoa Lucía Liliana Rodrigues Liliana Rodrigues Liliana Rodrigues José A. Aínsa José A. Aínsa |
| author_sort | Fernando Sanz-García |
| collection | DOAJ |
| description | Aminoglycoside acetyltransferases are important determinants of resistance to aminoglycoside antibiotics in most bacterial genera. In mycobacteria, however, aminoglycoside acetyltransferases contribute only partially to aminoglycoside susceptibility since they are related with low level resistance to these antibiotics (while high level aminoglycoside resistance is due to mutations in the ribosome). Instead, aminoglycoside acetyltransferases contribute to other bacterial functions, and this can explain its widespread presence along species of genus Mycobacterium. This review is focused on two mycobacterial aminoglycoside acetyltransferase enzymes. First, the aminoglycoside 2′-N-acetyltransferase [AAC(2′)], which was identified as a determinant of weak aminoglycoside resistance in M. fortuitum, and later found to be widespread in most mycobacterial species; AAC(2′) enzymes have been associated with resistance to cell wall degradative enzymes, and bactericidal mode of action of aminoglycosides. Second, the Eis aminoglycoside acetyltransferase, which was identified originally as a virulence determinant in M. tuberculosis (enhanced intracellular survival); Eis protein in fact controls production of pro-inflammatory cytokines and other pathways. The relation of Eis with aminoglycoside susceptibility was found after the years, and reaches clinical significance only in M. tuberculosis isolates resistant to the second-line drug kanamycin. Given the role of AAC(2′) and Eis proteins in mycobacterial biology, inhibitory molecules have been identified, more abundantly in case of Eis. In conclusion, AAC(2′) and Eis have evolved from a marginal role as potential drug resistance mechanisms into a promising future as drug targets. |
| first_indexed | 2024-12-22T19:21:29Z |
| format | Article |
| id | doaj.art-84950555c822450289135d3f1a2a2ed5 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-22T19:21:29Z |
| publishDate | 2019-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Microbiology |
| spelling | doaj.art-84950555c822450289135d3f1a2a2ed52022-12-21T18:15:21ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-01-011010.3389/fmicb.2019.00046422264Mycobacterial Aminoglycoside Acetyltransferases: A Little of Drug Resistance, and a Lot of Other RolesFernando Sanz-García0Ernesto Anoz-Carbonell1Ernesto Anoz-Carbonell2Esther Pérez-Herrán3Carlos Martín4Carlos Martín5Ainhoa Lucía6Ainhoa Lucía7Liliana Rodrigues8Liliana Rodrigues9Liliana Rodrigues10José A. Aínsa11José A. Aínsa12Departamento de Microbiología, Facultad de Medicina – Instituto Universitario de Investigación de Biocomputación y Física de Sistemas Complejos, Instituto de Investigación Sanitaria Aragón, Universidad de Zaragoza, Zaragoza, SpainDepartamento de Microbiología, Facultad de Medicina – Instituto Universitario de Investigación de Biocomputación y Física de Sistemas Complejos, Instituto de Investigación Sanitaria Aragón, Universidad de Zaragoza, Zaragoza, SpainDepartamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias – Instituto Universitario de Investigación de Biocomputación y Física de Sistemas Complejos, Universidad de Zaragoza, Zaragoza, SpainDepartamento de Microbiología, Facultad de Medicina – Instituto Universitario de Investigación de Biocomputación y Física de Sistemas Complejos, Instituto de Investigación Sanitaria Aragón, Universidad de Zaragoza, Zaragoza, SpainDepartamento de Microbiología, Facultad de Medicina – Instituto Universitario de Investigación de Biocomputación y Física de Sistemas Complejos, Instituto de Investigación Sanitaria Aragón, Universidad de Zaragoza, Zaragoza, SpainCentro de Investigación Biomédica en Red Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, SpainDepartamento de Microbiología, Facultad de Medicina – Instituto Universitario de Investigación de Biocomputación y Física de Sistemas Complejos, Instituto de Investigación Sanitaria Aragón, Universidad de Zaragoza, Zaragoza, SpainCentro de Investigación Biomédica en Red Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, SpainDepartamento de Microbiología, Facultad de Medicina – Instituto Universitario de Investigación de Biocomputación y Física de Sistemas Complejos, Instituto de Investigación Sanitaria Aragón, Universidad de Zaragoza, Zaragoza, SpainCentro de Investigación Biomédica en Red Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, SpainFundación Agencia Aragonesa para la Investigación y el Desarrollo, Zaragoza, SpainDepartamento de Microbiología, Facultad de Medicina – Instituto Universitario de Investigación de Biocomputación y Física de Sistemas Complejos, Instituto de Investigación Sanitaria Aragón, Universidad de Zaragoza, Zaragoza, SpainCentro de Investigación Biomédica en Red Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, SpainAminoglycoside acetyltransferases are important determinants of resistance to aminoglycoside antibiotics in most bacterial genera. In mycobacteria, however, aminoglycoside acetyltransferases contribute only partially to aminoglycoside susceptibility since they are related with low level resistance to these antibiotics (while high level aminoglycoside resistance is due to mutations in the ribosome). Instead, aminoglycoside acetyltransferases contribute to other bacterial functions, and this can explain its widespread presence along species of genus Mycobacterium. This review is focused on two mycobacterial aminoglycoside acetyltransferase enzymes. First, the aminoglycoside 2′-N-acetyltransferase [AAC(2′)], which was identified as a determinant of weak aminoglycoside resistance in M. fortuitum, and later found to be widespread in most mycobacterial species; AAC(2′) enzymes have been associated with resistance to cell wall degradative enzymes, and bactericidal mode of action of aminoglycosides. Second, the Eis aminoglycoside acetyltransferase, which was identified originally as a virulence determinant in M. tuberculosis (enhanced intracellular survival); Eis protein in fact controls production of pro-inflammatory cytokines and other pathways. The relation of Eis with aminoglycoside susceptibility was found after the years, and reaches clinical significance only in M. tuberculosis isolates resistant to the second-line drug kanamycin. Given the role of AAC(2′) and Eis proteins in mycobacterial biology, inhibitory molecules have been identified, more abundantly in case of Eis. In conclusion, AAC(2′) and Eis have evolved from a marginal role as potential drug resistance mechanisms into a promising future as drug targets.https://www.frontiersin.org/article/10.3389/fmicb.2019.00046/fullmycobacteriaaminoglycoside antibioticsaminoglycoside acetyltransferasedrug targetpathogenicityaminoglycoside resistance |
| spellingShingle | Fernando Sanz-García Ernesto Anoz-Carbonell Ernesto Anoz-Carbonell Esther Pérez-Herrán Carlos Martín Carlos Martín Ainhoa Lucía Ainhoa Lucía Liliana Rodrigues Liliana Rodrigues Liliana Rodrigues José A. Aínsa José A. Aínsa Mycobacterial Aminoglycoside Acetyltransferases: A Little of Drug Resistance, and a Lot of Other Roles Frontiers in Microbiology mycobacteria aminoglycoside antibiotics aminoglycoside acetyltransferase drug target pathogenicity aminoglycoside resistance |
| title | Mycobacterial Aminoglycoside Acetyltransferases: A Little of Drug Resistance, and a Lot of Other Roles |
| title_full | Mycobacterial Aminoglycoside Acetyltransferases: A Little of Drug Resistance, and a Lot of Other Roles |
| title_fullStr | Mycobacterial Aminoglycoside Acetyltransferases: A Little of Drug Resistance, and a Lot of Other Roles |
| title_full_unstemmed | Mycobacterial Aminoglycoside Acetyltransferases: A Little of Drug Resistance, and a Lot of Other Roles |
| title_short | Mycobacterial Aminoglycoside Acetyltransferases: A Little of Drug Resistance, and a Lot of Other Roles |
| title_sort | mycobacterial aminoglycoside acetyltransferases a little of drug resistance and a lot of other roles |
| topic | mycobacteria aminoglycoside antibiotics aminoglycoside acetyltransferase drug target pathogenicity aminoglycoside resistance |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.00046/full |
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