Abstract

Type IV secretion system (T4SS)-mediated horizontal gene transfer occurs in response to bacterial evolution and has been shown to play vital roles in gram-negative bacteria. Although bioinformatic analysis has revealed that T4SSs are widely distributed, there is limited knowledge regarding the biological function of the T4SS in gram-positive strains, especially in clinical strains. In this study, we established a conjugate genetic transfer model via T4SS in Streptococcus pneumoniae, an important clinical bacterial strain with high genomic plasticity, which is responsible for the increasing antimicrobial resistance and serotype replacement of this pathogen. By combining both bioinformatic and experimental approaches, we confirmed the function of the T4SS gene cassette in horizontal gene transfer, analyzed the distribution and evolutionary characteristics of the T4SS in S. pneumoniae, and proposed the concept of a ‘minimized’ T4SS in gram-positive bacteria. Furthermore, the genomic relationship between T4SSs and antimicrobial resistant (AMR) genes suggested that transfer of AMR genes might be associated with T4SSs and contribute to the evolution of S. pneumoniae. Our findings on the genetic structure and biological function of the T4SS in S. pneumoniae provides new insights into controlling the spread of multi-drug resistant bacteria, as well as aiding in the development of new antibiotics and vaccines. Funding Information: This work was supported by grants from the National Natural Science Foundation of China (81902025), the Beijing Postdoctoral Science Foundation (ZZ2019-19), the National Key Research and Development Project of China (2018YFE9102500) and the Capital Clinical Diagnosis and the Treatment Research and Application (Z201100005520040). Declaration of Interests: None to declare.

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