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Molecular Mechanism of Staphylococcus xylosus Resistance Against Tylosin and Florfenicol
1College of Veterinary Medicine, Northeast Agricultural University, Harbin, People's Republic of China.
Purpose:
Drug resistance presents an ever-increasing global public health threat that involves all major microbial pathogens and antimicrobial drugs. Strains that are resistant to multiple drugs pose severe clinical problems and cost lives. However, systematic studies on cross-resistance of Staphylococcus xylosus have been missing.
Methods:
Here, we investigated various mutations in the sequence of ribosomal proteins involved in cross-resistance. To understand this effect on a molecular basis and to further elucidate the role of cross-resistance, we computationally constructed the 3D model of the large ribosomal subunit from S. xylosus as well as its complexes with both tylosin and florfenicol. Meanwhile, all-atom molecular dynamics simulations was used. In addition, the regulation of protein networks also played an essential role in the development of cross-resistance in S. xylosus.
Results:
We discovered that the minimum inhibitory concentration against both tylosin and florfenicol of the mutant strain containing the insertion L22 97KRTSAIN98 changed dramatically. Further, we found that unique structural changes in the β-hairpin of L22 played a central role in this variant in the development of antibiotic resistance in S. xylosus. The regulation of protein networks also played an essential role in the development of cross-resistance in S. xylosus.
Conclusion:
Our work provides insightful views into the mechanism of S. xylosus resistance that could be useful for the development of the next generation of antibiotics.
Insights
This study reveals how specific mutations in Staphylococcus xylosus ribosomal protein L22 lead to cross-resistance against antibiotics like tylosin and florfenicol. Understanding these molecular mechanisms is key to developing new antimicrobial drugs.
Area of Science:
- Microbiology
- Molecular Biology
- Computational Biology
Background:
- Antimicrobial resistance is a growing global health crisis.
- Multidrug-resistant strains of bacteria, including Staphylococcus xylosus, present significant clinical challenges.
- Systematic research into Staphylococcus xylosus cross-resistance mechanisms has been limited.
Purpose of the Study:
- To investigate mutations in ribosomal proteins associated with cross-resistance in Staphylococcus xylosus.
- To elucidate the molecular basis of cross-resistance in Staphylococcus xylosus.
- To explore the role of protein network regulation in Staphylococcus xylosus cross-resistance.
Main Methods:
- Computational 3D modeling of the Staphylococcus xylosus large ribosomal subunit and its complexes with tylosin and florfenicol.
- All-atom molecular dynamics simulations.
- Analysis of mutations in ribosomal protein sequences.
Main Results:
- A specific mutation (insertion L22 97KRTSAIN98) significantly altered the minimum inhibitory concentration for tylosin and florfenicol.
- Unique structural changes in the L22 protein's β-hairpin were identified as crucial for this antibiotic resistance.
- Protein network regulation was confirmed as a significant factor in Staphylococcus xylosus cross-resistance.
Conclusions:
- The study provides novel insights into the molecular mechanisms driving Staphylococcus xylosus resistance to tylosin and florfenicol.
- Findings highlight the critical role of specific ribosomal protein mutations and structural alterations in conferring cross-resistance.
- This research could inform the development of novel antibiotics to combat drug-resistant bacteria.
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