Prevalence of Various Vaccine Candidate Proteins in Clinical Isolates of Streptococcus pneumoniae: Characterization of the Novel Pht Fusion Proteins PhtA/B and PhtA/D.

Kawaguchiya Kawaguchiya,Takahashi Takahashi,Kobayashi Kobayashi,Aung Aung,Shinagawa Shinagawa,Urushibara Urushibara

doi:10.3390/pathogens8040162

Kawaguchiya Kawaguchiya, Takahashi Takahashi + Show 4 more

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https://doi.org/10.3390/pathogens8040162

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Journal: Pathogens	Publication Date: Sep 24, 2019
Citations: 8	License type: CC BY 4.0

Affiliation: Sapporo Medical University

Abstract

Pneumococcal proteins unrelated to serotypes are considered to be candidates of antigens in next-generation vaccines. In the present study, the prevalence of vaccine candidate protein genes, along with serotypes and antimicrobial resistance determinants, was investigated in a total of 57 isolates obtained from a tertiary care hospital in Japan. All of the pediatric isolates and 76.6% of the adult isolates did not belong to PCV13 (a 13-valent pneumococcal conjugate vaccine) serotypes, and 70.2% of all isolates showed multidrug resistance. All of the isolates had ply, pavA, nanA, and nanB, and high prevalence was noted for the pspA and pspC genes (96.5% and 78.9%, respectively). Detection rates for the pneumococcal histidine triad protein (Pht) genes phtA, phtB, phtD, and phtE were 49.1%, 26.3%, 61.4%, and 100%, respectively. Two fusion-type genes, phtA/B and phtA/D, were identified, with a prevalence of 36.9% and 14.0%, respectively. These fusion types showed 78.1–90.0% nucleotide sequence identity with phtA, phtB, and phtD. The most prevalent pht profile was phtA + phtD + phtE (26.3%), followed by phtA/B + phtE (19.3%) and phtA/B + phtD + phtE (17.5%), while pht profiles including phtD and/or phtA/phtD were found in 71.9% of isolates. The present study revealed the presence of two fusion types of Pht and their unexpectedly high prevalence. These fusion types, as well as PhtA and PhtB, contained sequences similar to the B cell epitopes that have been previously reported for PhtD.

Highlights

Streptococcus pneumoniae occasionally causes both invasive and noninvasive pneumococcal disease (IPD and non-IPD, respectively), such as sepsis, meningitis, and community-acquired pneumonia [1], while this bacterium colonizes and persists on the human nasopharynx [2]
The purpose of the present study was to investigate the prevalence of vaccine candidate protein genes in clinical isolates of S. pneumoniae collected from IPD and non-IPD patients, along with serotypes and antimicrobial resistance
All of the pediatric isolates belonged to non-PCV13 serotypes, i.e., 15B (ST199; Netherlands15B -37 Pneumococcal Molecular Epidemiology Network (PMEN) clone), 23A

Summary

Introduction

Streptococcus pneumoniae (pneumococcus) occasionally causes both invasive and noninvasive pneumococcal disease (IPD and non-IPD, respectively), such as sepsis, meningitis, and community-acquired pneumonia [1], while this bacterium colonizes and persists on the human nasopharynx [2]. 13-valent pneumococcal conjugate vaccines (PCVs), both of which contain CPS as an immunogen, have. The unconjugated PPSV23 is widely offered to only adults because of poorer immunogenicity in children under 2 years of age [4,5], whereas the recently approved PCVs have been used in routine childhood vaccination programs across the world since 2000 [6]. Routine immunization with PCVs in children has greatly reduced the infections caused by pneumococci through the serotypes included in the vaccine (vaccine serotypes). Following the introduction of PCV7 and PCV13 in children, the isolation rate of pneumococci with nonvaccine types increased globally as a result of the vaccine selection pressure, and recent studies in different countries have reported the occurrence of immediate chronological changes in serotypes [7,8,9].

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