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Molecular level understanding of resistance to nalidixic acid in Salmonella enteric serovar typhimurium associates with the S83F sequence type

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Abstract

Nalidixic acid is an antibiotic drug used for treatment of Salmonellosis, a gastrointestinal infection. DNA gyrase subunit A (GyrA) of Salmonella typhimurium is the drug target for nalidixic acid. Resistance of GyrA to nalidixic acid, because of a point mutation in S. typhimurium, was recently reported. Substitution of Phe in place of Ser at locus 83 in GyrA of S. typhimurium has been experimentally associated with nalidixic acid resistance. Despite recent efforts, the mechanism of this resistance is not well understood. In this investigation we used computational techniques to address this shortcoming. Our results showed that contact with residue Arg 91 is certainly important for efficient binding of nalidixic acid to the target protein, and that mutation of this residue results in 180° rotation of the antibiotic in its binding pocket, around its own long axis. It is hoped these findings may enable development of new antibiotics against resistant forms of Salmonella.

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Acknowledgments

The authors thank the management of VIT University for providing the facilities, support, and constant encouragement to perform this work. The authors also thank Professor M.A. Mohamed Sahul Hameed, English Division, VIT University, for English editing and grammar corrections in our manuscript.

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  1. Industrial Biotechnology Division, School of Bio Sciences and Technology, VIT University, Vellore, 632014, Tamil Nadu, India

    B. Preethi & K. Ramanathan

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  2. K. Ramanathan
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Correspondence to K. Ramanathan.

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Preethi, B., Ramanathan, K. Molecular level understanding of resistance to nalidixic acid in Salmonella enteric serovar typhimurium associates with the S83F sequence type. Eur Biophys J 45, 35–44 (2016). https://doi.org/10.1007/s00249-015-1073-2

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  • DOI: https://doi.org/10.1007/s00249-015-1073-2

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