Molecular Mechanism of Staphylococcus Xylosus Resistance Against Tylosin and Florfenicol

Abstract As a result of evolution, certain microbes develop resistance against antimicrobial treatment. The antimicrobial resistance (AMR) threatens the effective prevention and treatment of an ever-increasing range of severe infections caused by microbes such as bacteria, viruses, fungi and other parasites. The resistance of Staphylococcus xylosus (S. xylosus) against antibiotic treatment is one of the major causes of the world-wide antibiotic crisis and has remained to be well understood at the molecular level. In order to fill this gap, we investigated various mutations in the sequence of ribosomal proteins involved cross resistance. We discovered that for the mutant containing the insertion L22 97KRTSAIN98 the minimum inhibitory concentration against both tylosin and florfenicol changed dramatically. 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. Using all-atom molecular dynamics simulations, we found that unique structural changes in the β hairpin of L22 played a central role of this variant in the development of antibiotic resistance in S. xylosus. In addition, the regulation of protein network also played an essential role in the development of cross resistance in S. xylosus. Our work provides insightful views into the mechanism of S. xylosus resistance which could be useful for the development of the next generation of antibiotics.