Pan-Genome-Wide Association Study of Serotype 19A Pneumococci Identifies Disease-Associated Genes
ABSTRACT Despite the widespread implementation of pneumococcal vaccines, hypervirulent Streptococcus pneumoniae serotype 19A is endemic worldwide. It is still unclear whether specific genetic elements contribute to complex pathogenicity of serotype 19A isolates. We performed a large-scale pan-genome...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-08-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.04073-22 |
| _version_ | 1797741739489886208 |
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| author | Ting Li Jiayin Huang Shimin Yang Jianyu Chen Zhenjiang Yao Minghao Zhong Xinguang Zhong Xiaohua Ye |
| author_facet | Ting Li Jiayin Huang Shimin Yang Jianyu Chen Zhenjiang Yao Minghao Zhong Xinguang Zhong Xiaohua Ye |
| author_sort | Ting Li |
| collection | DOAJ |
| description | ABSTRACT Despite the widespread implementation of pneumococcal vaccines, hypervirulent Streptococcus pneumoniae serotype 19A is endemic worldwide. It is still unclear whether specific genetic elements contribute to complex pathogenicity of serotype 19A isolates. We performed a large-scale pan-genome-wide association study (pan-GWAS) of 1,292 serotype 19A isolates sampled from patients with invasive disease and asymptomatic carriers. To address the underlying disease-associated genotypes, a comprehensive analysis using three methods (Scoary, a linear mixed model, and random forest) was performed to compare disease and carriage isolates to identify genes consistently associated with disease phenotype. By using three pan-GWAS methods, we found consensus on statistically significant associations between genotypes and disease phenotypes (disease or carriage), with a subset of 30 consistently significant disease-associated genes. The results of functional annotation revealed that these disease-associated genes had diverse predicted functions, including those that participated in mobile genetic elements, antibiotic resistance, virulence, and cellular metabolism. Our findings suggest the multifactorial pathogenicity nature of this hypervirulent serotype and provide important evidence for the design of novel protein-based vaccines to prevent and control pneumococcal disease. IMPORTANCE It is important to understand the genetic and pathogenic characteristics of S. pneumoniae serotype 19A, which may provide important information for the prevention and treatment of pneumococcal disease. This global large-sample pan-GWAS study has identified a subset of 30 consistently significant disease-associated genes that are involved in mobile genetic elements, antibiotic resistance, virulence, and cellular metabolism. These findings suggest the multifactorial pathogenicity nature of hypervirulent S. pneumoniae serotype 19A isolates and provide implications for the design of novel protein-based vaccines. |
| first_indexed | 2024-03-12T14:31:00Z |
| format | Article |
| id | doaj.art-1117264afed2435cbb93e0d402a867a1 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-12T14:31:00Z |
| publishDate | 2023-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-1117264afed2435cbb93e0d402a867a12023-08-17T13:04:14ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-08-0111410.1128/spectrum.04073-22Pan-Genome-Wide Association Study of Serotype 19A Pneumococci Identifies Disease-Associated GenesTing Li0Jiayin Huang1Shimin Yang2Jianyu Chen3Zhenjiang Yao4Minghao Zhong5Xinguang Zhong6Xiaohua Ye7School of Public Health, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Public Health, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Public Health, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Public Health, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Public Health, Guangdong Pharmaceutical University, Guangzhou, ChinaDepartment of Prevention and Health Care, The Sixth People’s Hospital of Dongguan City, Guangdong, ChinaDepartment of Prevention and Health Care, The Sixth People’s Hospital of Dongguan City, Guangdong, ChinaSchool of Public Health, Guangdong Pharmaceutical University, Guangzhou, ChinaABSTRACT Despite the widespread implementation of pneumococcal vaccines, hypervirulent Streptococcus pneumoniae serotype 19A is endemic worldwide. It is still unclear whether specific genetic elements contribute to complex pathogenicity of serotype 19A isolates. We performed a large-scale pan-genome-wide association study (pan-GWAS) of 1,292 serotype 19A isolates sampled from patients with invasive disease and asymptomatic carriers. To address the underlying disease-associated genotypes, a comprehensive analysis using three methods (Scoary, a linear mixed model, and random forest) was performed to compare disease and carriage isolates to identify genes consistently associated with disease phenotype. By using three pan-GWAS methods, we found consensus on statistically significant associations between genotypes and disease phenotypes (disease or carriage), with a subset of 30 consistently significant disease-associated genes. The results of functional annotation revealed that these disease-associated genes had diverse predicted functions, including those that participated in mobile genetic elements, antibiotic resistance, virulence, and cellular metabolism. Our findings suggest the multifactorial pathogenicity nature of this hypervirulent serotype and provide important evidence for the design of novel protein-based vaccines to prevent and control pneumococcal disease. IMPORTANCE It is important to understand the genetic and pathogenic characteristics of S. pneumoniae serotype 19A, which may provide important information for the prevention and treatment of pneumococcal disease. This global large-sample pan-GWAS study has identified a subset of 30 consistently significant disease-associated genes that are involved in mobile genetic elements, antibiotic resistance, virulence, and cellular metabolism. These findings suggest the multifactorial pathogenicity nature of hypervirulent S. pneumoniae serotype 19A isolates and provide implications for the design of novel protein-based vaccines.https://journals.asm.org/doi/10.1128/spectrum.04073-22Streptococcus pneumoniaepneumococcusbacterial genomicsgenome-wide association studypathogenicityinvasive pneumococcal disease |
| spellingShingle | Ting Li Jiayin Huang Shimin Yang Jianyu Chen Zhenjiang Yao Minghao Zhong Xinguang Zhong Xiaohua Ye Pan-Genome-Wide Association Study of Serotype 19A Pneumococci Identifies Disease-Associated Genes Microbiology Spectrum Streptococcus pneumoniae pneumococcus bacterial genomics genome-wide association study pathogenicity invasive pneumococcal disease |
| title | Pan-Genome-Wide Association Study of Serotype 19A Pneumococci Identifies Disease-Associated Genes |
| title_full | Pan-Genome-Wide Association Study of Serotype 19A Pneumococci Identifies Disease-Associated Genes |
| title_fullStr | Pan-Genome-Wide Association Study of Serotype 19A Pneumococci Identifies Disease-Associated Genes |
| title_full_unstemmed | Pan-Genome-Wide Association Study of Serotype 19A Pneumococci Identifies Disease-Associated Genes |
| title_short | Pan-Genome-Wide Association Study of Serotype 19A Pneumococci Identifies Disease-Associated Genes |
| title_sort | pan genome wide association study of serotype 19a pneumococci identifies disease associated genes |
| topic | Streptococcus pneumoniae pneumococcus bacterial genomics genome-wide association study pathogenicity invasive pneumococcal disease |
| url | https://journals.asm.org/doi/10.1128/spectrum.04073-22 |
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