Molecular Characterization Based on Whole-Genome Sequencing of Streptococcus pneumoniae in Children Living in Southwest China During 2017-2019

Abstract

BackgroundStreptococcus pneumoniae is an important pathogen causing high morbidity and high mortality in children and undergoes frequent recombination for capsule switching to neutralize the 13-valent pneumococcal conjugate vaccine (PCV13). This study aimed to investigate the prevalence, and molecular characteristics including serotypes and antibiotic susceptibility of S. pneumoniae isolated from children living in Southwest China from 2017 to 2019 to facilitate the selection of effective vaccine formulations and appropriate antibiotic treatment regimens.MethodsThis study was conducted at West China Second University Hospital (Chengdu, Sichuan Province, China), Zunyi Medical University Third Affiliated Hospital/First People’s Hospital of Zunyi (Zunyi, Guizhou Province, China) and Chengdu Jinjiang District Maternal and Child Healthcare Hospital (Chengdu, Sichuan Province, China). Demographic and clinical characteristics of children infected with S. pneumoniae were collected and analysed. Next-generation sequencing and sequence analysis were used to determine the serotypes, sequence types, antibiotic resistance and potential protein vaccine target genes of the pneumococcal isolates. The coverage rate provided by PCV13 was estimated by calculating the percentage of the specific serotypes that were specifically the PCV13-included serotypes. Antimicrobial susceptibility was determined by the microdilution broth method.ResultsThe most prevalent pneumococcal serotypes were 19F (25.8%), 19A (14.1%), 6B (12.5%), 6A (9.4%) and 14 (7.8%). The predominant STs were ST271 (23.3%), ST320 (15.5%) and ST90 (8.6%), dominated by the clonal complex Taiwan19F-14 (39.1%). The coverage rate of PCV13 was 77.3% in all the isolates, with relatively higher values in invasive isolates (86.4%). Over the decade, the rates of resistance to penicillin, amoxicillin and cefotaxime were 5.6%, 5.3% and 5.1%, respectively, with significantly higher values in invasive isolates (22.4%, 14.9% and 11.9%). Almost all the isolates were resistant to erythromycin (99.1%) and clindamycin (95.9%). All isolates carried virulence-related genes, including ply, psaA, piaA, piuA, phtE, nanA, pepO, danJ, pvaA, clpP, pcsB, stkP, potD, and strH. The carriage of virulence and resistance genes varied among serotypes and clades, with serotype 19F/ST271 showing higher resistance to antibiotics and being more likely to carry pilus genes and other virulence genes.ConclusionThese data provide valuable information for the understanding of pneumococcal pathogenesis, antimicrobial resistance and the development of protein-based vaccines against pneumococcal infection.

Molecular Characterization of Predominant Serotypes, Drug Resistance, and Virulence Genes of Streptococcus pneumoniae Isolates From East China

“…In this study, the PNC non-susceptible rate among the 309 S. pneumoniae isolates was as high as 81.6% (63.2% intermediate and 18.4% resistant), but the CTX non-susceptible rate was only 14.2% (11.6% intermediate and 2.6% resistant). The ETM and AZM resistance rates among the 309 S. pneumoniae isolates were 95.8 and 96.1%, which are similar to those from Western China (94.3%), North China (95–98.2%), and Southwest China (99.1%) ( Zhao et al, 2020 ; Liang et al, 2021 ; Yan et al, 2021 ; Zhou et al, 2022 ) but significantly higher than those from Southeast Asia (38.5–42.0%), India (37.0%), United States (37.1%), and Latin America (43.2%) ( Mendes et al, 2016 ; Singh et al, 2017 ; Moreno et al, 2020 ; Wangirapan et al, 2020 ; Dzaraly et al, 2021 ). In addition, 96.1% of the 309 S. pneumoniae isolates in this study showed different multidrug resistance patterns, which is also similar to those from Western China (93.8%) ( Liang et al, 2021 ), but significantly higher than those from South Korea (46.2%), Malaysia (18.0%), and Latin America (44.3%) ( Park et al, 2019 ; Moreno et al, 2020 ; Dzaraly et al, 2021 ).…”

“…19F, 6B, 23F, and 19A were the common serotypes observed among the S. pneumoniae isolates in Western China, while 19F, 19A, and 23F were the predominant serotypes among the S. pneumoniae isolates in North China ( Zhao et al, 2020 ; Liang et al, 2021 ; Zhou et al, 2022 ). In the different areas of Southwest China, 19F and 19A were the predominant pneumococcal serotypes ( Shen et al, 2017 ; Ma et al, 2021 ; Yan et al, 2021 ). In addition, serotypes 12F, 3, 23A, 19A, 10A, 6C, and 22F and serotypes 3, 19A, and 11A were the commonly found among the S. pneumoniae isolates from Japan and South Korea, respectively ( Park et al, 2019 ; Heo et al, 2020 ; Yanagihara et al, 2021 ).…”

“…However, β-lactam antibiotic resistance rates of S. pneumoniae isolates from different areas and countries have a large diversity. For example, PNC and CTX resistance rates among the S. pneumoniae isolates from Western China, North China, and Southwest China were 1.2–79.9% and 0.5–28.6% ( Shen et al, 2017 ; Zhao et al, 2020 ; Liang et al, 2021 ; Yan et al, 2021 ; Zhou et al, 2022 ), while the PNC resistance rates among the S. pneumoniae isolates from East Asia (Japan and South Korea), Southeast Asia (Thailand and Malaysia), India, United States, Europe, and Latin America were 1.7–22.8%, 4–83.1%, 10%, 10.8%, 19.4%, and 68.6%, respectively ( Mendes et al, 2016 ; Yahiaoui et al, 2016 ; Singh et al, 2017 ; Park et al, 2019 ; Moreno et al, 2020 ; Wangirapan et al, 2020 ; Dzaraly et al, 2021 ; Yanagihara et al, 2021 ). In this study, the PNC non-susceptible rate among the 309 S. pneumoniae isolates was as high as 81.6% (63.2% intermediate and 18.4% resistant), but the CTX non-susceptible rate was only 14.2% (11.6% intermediate and 2.6% resistant).…”

Construction and protective efficacy of a novel Streptococcus pneumoniae fusion protein vaccine NanAT1-TufT1-PlyD4

“…In our previous studies, we successfully confirmed that all three proteins are conserved in clinical pneumococcal strains. These encouraging results prompted us to conduct further research, such as constructing the functional epitopes of these proteins and evaluating the immune responses induced by fusion protein vaccines based on the three proteins ( 26 ).…”

Changes in Streptococcus pneumoniae infection in children before and after the COVID-19 pandemic in Zhengzhou, China

“…In addition, invasive pneumococcal diseases (IPDs) are the leading cause of death in children under 5 years of age. 5 , 6 , 7 The World Health Organization (WHO) estimates that approximately 1.6 million children die each year from Streptococcus pneumoniae infectious diseases, including 700,000 to 1 million children under 5 years of age, most of whom are under 2 years of age. 5 With the widespread use of pneumococcal conjugate vaccine (PCV) in children in many countries and regions,The number of deaths among children from Streptococcus pneumoniae-related diseases has declined.…”