Deep-sequencing Identification Of Multi-drug Resistance Mechanisms For The High Antibiotic-resistance Strain Streptococcus Suis R61&Coevolution Study Of Mitochondria Respiratory Chain Proteins:Toward The Understanding Of Protein-Protein Interaction

Streptococcus suis (S. suis) infections have been considered a major problem worldwide in the swine industry. Moreover, S. suis is a zoonotic pathogen that causes occasional cases of meningitis and sepsis in humans. Under the directional selection imposed by drugs, drug-sensitive pathogens frequently evolve resistance. Currently, antibiotic-resistant S. suis strains continually arise and their increasing prevalence would pose significant clinical and societal challenges.In our study, we sequenced one multi-drug resistant S. suis strain R61and one fully drug-sensitive S. suis strain A7tested by18antibiotics. In order to investigate the relationships between genome dynamics and resistance mechanism, comparative genomic analysis of S. suis strains was performed. Our analysis indicates that the multi-drug resistant strain R61has evolved mainly3categories of resistance patterns, responsible for commonly used antibiotics against S. suis infection. Additionally, some antibiotic resistance genes were identified as horizontally acquired genes from divergent species.Our analysis reveals that strain R61is phylogenetically distinct from other strains and the genome of strain R61exhibits extreme levels of evolutionary plasticity, with high levels of gene gain and loss during strain evolution. Comparative genomic analysis of diverse drug-resistant phenotypes of S. suis strains provide evidence that horizontal gene transfer is an important evolutionary force in shaping the genome of multi-drug resistance strain R61. In the study, we discovered some novel or previous unconsidered mutations that are strong candidates for drug resistance. We believe that these mutations will provide crucial clues for designing new-style vaccines against the pathogen. Meanwhile, our work provides a clear demonstration that the use of drug has contributed to the evolution of multi-drug resistant strain R61. Coevolution can be seen as the interdependency between evolutionary histories, In the context of protein evolution, functional correlation proteins are ever-present coordinated evolutionary characters without disruption of organismal integrity. As to complex system, there are two forms of protein-protein interactions in vivo, which refer to inter-complex interaction and intra-complex interaction, In this paper, we studied the difference of coevolutionary characters between inter-complex interaction and intra-complex interaction using "mirror tree" method on the respiratory chain (RC) proteins. We divided the correlation coefficients of every pairwise RC proteins into two groups corresponding to the binary protein-protein interaction in intra-complex and the binary protein-protein interaction in inter-complex, respectively. A dramatically discrepancy is detected between the coevolution characters of the two sets of protein interactions (Wilcoxon test,p-value=4.4×10-6). Our finding reveals some critical information on coevolutionary study and assists the mechanical investigation of protein-protein interaction. Furthermore, the results also provide some unique clue for supermolecular organization of protein complexes in the mitochondrial inner membrane. More detailed binding sites map and genome information of nuclear encoded RC proteins will be extraordinary valuable for the further mitochondria dynamics study.