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Catabolism of aromatic β-glucosides by bacteria can lead to antibiotics resistance

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Abstract

Antimicrobial resistance is a serious public health threat worldwide today. Escherichia coli is known to resist low doses of antibiotics in the presence of sodium salicylate and related compounds by mounting non-heritable transient phenotypic antibiotic resistance (PAR). In the present study, we demonstrate that Bgl+ bacterial strains harboring a functional copy of the β-glucoside (bgl) operon and are actively hydrolyzing plant-derived aromatic β-glucosides such as salicin show PAR to low doses of antibiotics. The aglycone released during metabolism of aromatic β-glucosides is responsible for conferring this phenotype by de-repressing the multiple antibiotics resistance (mar) operon. We also show that prolonged exposure of Bgl+ bacteria to aromatic β-glucosides in the presence of sub-lethal doses of antibiotics can lead to a significant increase in the frequency of mutants that show heritable resistance to higher doses of antibiotics. Although heritable drug resistance in many cases is known to reduce the fitness of the carrier strain, we did not see a cost associated with resistance in the mutants, most of which carry clinically relevant mutations. These findings indicate that the presence of the activated form of the bgl operon in the genome facilitates the survival of bacteria in environments in which both aromatic β-glucosides and antibiotics are present.

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Abbreviations

PAR:

Phenotypic antibiotic resistance

NaSal:

Sodium salicylate

SG:

Saligenin

MIC:

Minimal inhibitory concentration

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Acknowledgements

This study was funded by the Department of Biotechnology (DBT) through a partnership programme with the Indian Institute of Science. The authors are also grateful to the Department of Science and Technology (DST-FIST) and the Universities Grants Commission (UGC) for infrastructural support. KV is a recipient of a research fellowship from the Indian Institute of Science. SM acknowledges additional financial support from the Indian Institute of Science.

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Correspondence to S. Mahadevan.

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Communicated by Erko Stackebrandt.

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Vashishtha, K., Mahadevan, S. Catabolism of aromatic β-glucosides by bacteria can lead to antibiotics resistance. Arch Microbiol 202, 1301–1315 (2020). https://doi.org/10.1007/s00203-020-01836-9

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