Reducing bacterial antibiotic resistance by targeting bacterial metabolic pathways and disrupting RND efflux pump activity
Reducir la resistencia a los antibióticos bacterianos al dirigirse a las vías metabólicas bacterianas e interrumpir la actividad de la bomba de salida de RND
Tatiana Hillman
Abstract
Antibiotic resistance is a significant issue for the medical community, worldwide. Many bacteria develop drug resistance by utilizing multidrug resistant or MDR efflux pumps that can export antibiotics from bacterial cells. Antibiotics are expelled from bacteria by efflux pumps a part of the resistance nodulation division (RND) family. Types of RND efflux pumps include the AcrAB-TolC tripartite protein pump. There are an excessive number of antibiotic compounds that have been discovered; however, only a few antibiotics are effective against MDR bacteria. Many bacteria become drug resistant when sharing genes that encode MDR efflux pump expression. MDR efflux pump encoding genes are incorporated into plasmids and then shared among bacteria. As a consequence, advancements in genetic engineering can sufficiently target and edit pathogenic bacterial genomes for perturbing drug resistance mechanisms. In this perspective and review, support will be provided for utilizing genetic modifications as an antimicrobial approach and tool that may effectively combat bacterial MDR. Ayhan et al. found that deleting acrB, acrA, and tolC increased the levels of antibiotic sensitivity in Escherichia coli. Researchers also found that glucose, glutamate, and fructose all induced the absorption of antibiotics by upregulating the gene expression of maeA and maeB that is a part of the MAL-pyruvate pathway. Therefore, the current perspective and review will discuss the potential efficacy of reducing antibiotic resistance by inhibiting genes that encode efflux protein pump expression while simultaneously upregulating metabolic genes for increased antibiotic uptake.
Keywords
Resumen
La resistencia a los antibióticos es un problema importante para la comunidad médica en todo el mundo. Muchas bacterias desarrollan resistencia a los fármacos mediante el uso de bombas de eflujo MDR o resistentes a múltiples fármacos que pueden exportar antibióticos de las células bacterianas. Los antibióticos se expulsan de las bacterias mediante bombas de eflujo que forman parte de la familia de la división de nodulación de resistencia (RND). Los tipos de bombas de eflujo RND incluyen la bomba de proteínas tripartita AcrAB-TolC. Hay un número excesivo de compuestos antibióticos que se han descubierto; sin embargo, solo unos pocos antibióticos son eficaces contra la bacteria MDR. Muchas bacterias se vuelven resistentes a los fármacos cuando comparten genes que codifican la expresión de la bomba de eflujo MDR. Los genes que codifican la bomba de eflujo MDR se incorporan a los plásmidos y luego se comparten entre las bacterias. Como consecuencia, los avances en la ingeniería genética pueden apuntar y editar suficientemente los genomas bacterianos patógenos para perturbar los mecanismos de resistencia a los medicamentos. En esta perspectiva y revisión, se brindará apoyo para utilizar modificaciones genéticas como un enfoque y una herramienta antimicrobianos que pueden combatir eficazmente la MDR bacteriana. Ayhan y col. encontraron que la eliminación de acrB, acrA y tolC aumentaba los niveles de sensibilidad a los antibióticos en Escherichia coli. Los investigadores también encontraron que la glucosa, el glutamato y la fructosa inducían la absorción de antibióticos al regular al alza la expresión génica de maeA y maeB que es parte de la vía MAL-piruvato. Por lo tanto, la perspectiva actual y la revisión discutirán la eficacia potencial de reducir la resistencia a los antibióticos al inhibir los genes que codifican la expresión de la bomba de proteínas de salida y, al mismo tiempo, regular al alza los genes metabólicos para una mayor absorción de antibióticos.
Palabras clave
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Submitted date:
11/04/2021
Reviewed date:
12/15/2021
Accepted date:
01/02/2022
Publication date:
01/04/2022
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