Abstract
Staphylococcus xylosus is a gram-positive bacterium that has attracted much attention due to its increasing clinical appearance, frequently associated with serious multidrug resistance cases. L-lactate dehydrogenase (LDH) has been related to drug resistance in several bacterial species. However, the mechanism of multidrug resistance in S. xylosus remains unclear as well as the involvement of LDH in such resistance. To explore the relationship between multidrug resistance and LDH in S. xylosus, we used tylosin-resistant S. xylosus as the parent strain to construct ldh knockout and complemented strains. Then, we tested their resistance to macrolides, lincosamides, tetracyclines, and aminoglycosides. In addition, the enzyme activity, metabolite content, and transcriptional level of key genes involved in the TCA cycle and thioredoxin system were determined to clarify the mechanism of resistance. We observed that the resistance to multiple antibiotics increased significantly after ldh knockout, especially that to lincomycin, whereas antibiotic sensitivity was partially restored in the complemented strain. The levels of pyruvate, nicotinamide adenine dinucleotide, and reactive oxygen species decreased significantly upon ldh knockout, and the activity of isocitrate dehydrogenase and malate dehydrogenase decreased. These results indicate that the lack of LDH promotes multidrug resistance in S. xylosus by inhibiting the TCA cycle and regulating the thioredoxin system.
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Acknowledgements
We thank Prof. Rui Zhou (Huazhong Agricultural University) for the generous donation of the pBT2 vector used in the course of this study. We would like to thank Editage (www.editage.cn) for English language editing.
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The study was funded by the National Natural Science Foundation of China (Grant numbers. 31772787 and 3190190314) and the “Young Talents” Project of Northeast Agricultural University (19QC24).
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YL and XL conceived and designed the experiments; JW, YZ, CD, LL, and MC performed the experiments; ZY analyzed the data and wrote the manuscript; GB-O, RC, EN, and ZY revised the discussion and proofread the manuscript.
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Yuan, Z., Wang, J., Che, R. et al. Relationship between L-lactate dehydrogenase and multidrug resistance in Staphylococcus xylosus. Arch Microbiol 204, 91 (2022). https://doi.org/10.1007/s00203-021-02625-8
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DOI: https://doi.org/10.1007/s00203-021-02625-8