Comparative genomic analysis of multidrug-resistant Streptococcus pneumoniae isolates

Fen Pan; Hong Zhang; Xiaoyan Dong; Weixing Ye; Ping He; Shulin Zhang; Jeff Xianchao Zhu; Nanbert Zhong

doi:10.2147/IDR.S147858

Comparative genomic analysis of multidrug-resistant Streptococcus pneumoniae isolates

Infect Drug Resist. 2018 May 3:11:659-670. doi: 10.2147/IDR.S147858. eCollection 2018.

Authors

Fen Pan¹, Hong Zhang¹, Xiaoyan Dong², Weixing Ye³, Ping He⁴, Shulin Zhang⁴, Jeff Xianchao Zhu⁵, Nanbert Zhong^{1

2

6}

Affiliations

¹ Department of Clinical Laboratory, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, China.
² Department of Respiratory, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, China.
³ Shanghai Personal Biotechnology Co., Ltd, Shanghai, China.
⁴ Department of Medical Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Zhejiang Bioruida Biotechnology co. Ltd, Zhejiang, China.
⁶ New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.

Abstract

Introduction: Multidrug resistance in Streptococcus pneumoniae has emerged as a serious problem to public health. A further understanding of the genetic diversity in antibiotic-resistant S. pneumoniae isolates is needed.

Methods: We conducted whole-genome resequencing for 25 pneumococcal strains isolated from children with different antimicrobial resistance profiles. Comparative analysis focus on detection of single-nucleotide polymorphisms (SNPs) and insertions and deletions (indels) was conducted. Moreover, phylogenetic analysis was applied to investigate the genetic relationship among these strains.

Results: The genome size of the isolates was ~2.1 Mbp, covering >90% of the total estimated size of the reference genome. The overall G+C% content was ~39.5%, and there were 2,200-2,400 open reading frames. All isolates with different drug resistance profiles harbored many indels (range 131-171) and SNPs (range 16,103-28,128). Genetic diversity analysis showed that the variation of different genes were associated with specific antibiotic resistance. Known antibiotic resistance genes (pbps, murMN, ciaH, rplD, sulA, and dpr) were identified, and new genes (regR, argH, trkH, and PTS-EII) closely related with antibiotic resistance were found, although these genes were primarily annotated with functions in virulence as well as carbohydrate and amino acid transport and metabolism. Phylogenetic analysis unambiguously indicated that isolates with different antibiotic resistance profiles harbored similar genetic backgrounds. One isolate, 14-LC.ER1025, showed a much weaker phylogenetic relationship with the other isolates, possibly caused by genomic variation.

Conclusion: In this study, although pneumococcal isolates had similar genetic backgrounds, strains were diverse at the genomic level. These strains exhibited distinct variations in their indel and SNP compositions associated with drug resistance.

Keywords: SNPs; Streptococcus pneumoniae; antimicrobial resistance; insertions/deletions; phylogenetic analysis; whole-genome sequencing.