Whole-Genome Analysis of Bordetella pertussis MT27 Isolates from School-Associated Outbreaks: Single-Nucleotide Polymorphism Diversity and Threshold of the Outbreak Strains
ABSTRACT Bordetella pertussis, the causative agent of whooping cough, can cause pertussis outbreaks in humans, especially in school-aged children. Here, we performed whole-genome sequencing of 51 B. pertussis isolates (epidemic strain MT27) collected from patients infected during 6 school-associated...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-06-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.04065-22 |
| _version_ | 1797803390266245120 |
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| author | Kazunari Kamachi Kentaro Koide Nao Otsuka Masataka Goto Tsuyoshi Kenri |
| author_facet | Kazunari Kamachi Kentaro Koide Nao Otsuka Masataka Goto Tsuyoshi Kenri |
| author_sort | Kazunari Kamachi |
| collection | DOAJ |
| description | ABSTRACT Bordetella pertussis, the causative agent of whooping cough, can cause pertussis outbreaks in humans, especially in school-aged children. Here, we performed whole-genome sequencing of 51 B. pertussis isolates (epidemic strain MT27) collected from patients infected during 6 school-associated outbreaks lasting less than 4 months. We compared their genetic diversity with that of 28 sporadic isolates (non-outbreak MT27 isolates) based on single-nucleotide polymorphisms (SNPs). Our temporal SNP diversity analysis revealed a mean SNP accumulation rate (time-weighted average) of 0.21 SNPs/genome/year during the outbreaks. The outbreak isolates showed a mean of 0.74 SNP differences (median, 0; range, 0 to 5) between 238 isolate pairs, whereas the sporadic isolates had a mean of 16.12 SNP differences (median, 17; range 0 to 36) between 378 isolate pairs. A low SNP diversity was observed in the outbreak isolates. Receiver operating characteristic analysis demonstrated that the optimal cutoff value to distinguish between the outbreak and sporadic isolates was 3 SNPs (Youden’s index of 0.90 with a true-positive rate of 0.97 and a false-positive rate of 0.07). Based on these results, we propose an epidemiological threshold of ≤3 SNPs per genome as a reliable marker of B. pertussis strain identity during pertussis outbreaks that span less than 4 months. IMPORTANCE Bordetella pertussis is a highly infectious bacterium that easily causes pertussis outbreaks in humans, especially in school-aged children. In detection and investigation of outbreaks, excluding non-outbreak isolates is important for understanding the bacterial transmission routes. Currently, whole-genome sequencing is widely used for outbreak investigations, and the genetic relatedness of outbreak isolates is assessed based on differences in the number of single-nucleotide polymorphisms (SNPs) in the genomes of different isolates. The optimal SNP threshold defining strain identity has been proposed for many bacterial pathogens, but not for B. pertussis. In this study, we performed whole-genome sequencing of 51 B. pertussis outbreak isolates and identified a genetic threshold of ≤3 SNPs per genome as a marker defining the strain identity during pertussis outbreaks. This study provides a useful marker for identifying and analyzing pertussis outbreaks and can serve as a basis for future epidemiological studies on pertussis. |
| first_indexed | 2024-03-13T05:21:15Z |
| format | Article |
| id | doaj.art-5c3b17d97ce44b11b3ce696135e02661 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-13T05:21:15Z |
| publishDate | 2023-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-5c3b17d97ce44b11b3ce696135e026612023-06-15T13:18:32ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-06-0111310.1128/spectrum.04065-22Whole-Genome Analysis of Bordetella pertussis MT27 Isolates from School-Associated Outbreaks: Single-Nucleotide Polymorphism Diversity and Threshold of the Outbreak StrainsKazunari Kamachi0Kentaro Koide1Nao Otsuka2Masataka Goto3Tsuyoshi Kenri4Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Bacteriology II, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Bacteriology II, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Bacteriology II, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Bacteriology II, National Institute of Infectious Diseases, Tokyo, JapanABSTRACT Bordetella pertussis, the causative agent of whooping cough, can cause pertussis outbreaks in humans, especially in school-aged children. Here, we performed whole-genome sequencing of 51 B. pertussis isolates (epidemic strain MT27) collected from patients infected during 6 school-associated outbreaks lasting less than 4 months. We compared their genetic diversity with that of 28 sporadic isolates (non-outbreak MT27 isolates) based on single-nucleotide polymorphisms (SNPs). Our temporal SNP diversity analysis revealed a mean SNP accumulation rate (time-weighted average) of 0.21 SNPs/genome/year during the outbreaks. The outbreak isolates showed a mean of 0.74 SNP differences (median, 0; range, 0 to 5) between 238 isolate pairs, whereas the sporadic isolates had a mean of 16.12 SNP differences (median, 17; range 0 to 36) between 378 isolate pairs. A low SNP diversity was observed in the outbreak isolates. Receiver operating characteristic analysis demonstrated that the optimal cutoff value to distinguish between the outbreak and sporadic isolates was 3 SNPs (Youden’s index of 0.90 with a true-positive rate of 0.97 and a false-positive rate of 0.07). Based on these results, we propose an epidemiological threshold of ≤3 SNPs per genome as a reliable marker of B. pertussis strain identity during pertussis outbreaks that span less than 4 months. IMPORTANCE Bordetella pertussis is a highly infectious bacterium that easily causes pertussis outbreaks in humans, especially in school-aged children. In detection and investigation of outbreaks, excluding non-outbreak isolates is important for understanding the bacterial transmission routes. Currently, whole-genome sequencing is widely used for outbreak investigations, and the genetic relatedness of outbreak isolates is assessed based on differences in the number of single-nucleotide polymorphisms (SNPs) in the genomes of different isolates. The optimal SNP threshold defining strain identity has been proposed for many bacterial pathogens, but not for B. pertussis. In this study, we performed whole-genome sequencing of 51 B. pertussis outbreak isolates and identified a genetic threshold of ≤3 SNPs per genome as a marker defining the strain identity during pertussis outbreaks. This study provides a useful marker for identifying and analyzing pertussis outbreaks and can serve as a basis for future epidemiological studies on pertussis.https://journals.asm.org/doi/10.1128/spectrum.04065-22Bordetella pertussisoutbreak isolatesingle-nucleotide polymorphismSNP diversitySNP thresholdwhole-genome sequencing |
| spellingShingle | Kazunari Kamachi Kentaro Koide Nao Otsuka Masataka Goto Tsuyoshi Kenri Whole-Genome Analysis of Bordetella pertussis MT27 Isolates from School-Associated Outbreaks: Single-Nucleotide Polymorphism Diversity and Threshold of the Outbreak Strains Microbiology Spectrum Bordetella pertussis outbreak isolate single-nucleotide polymorphism SNP diversity SNP threshold whole-genome sequencing |
| title | Whole-Genome Analysis of Bordetella pertussis MT27 Isolates from School-Associated Outbreaks: Single-Nucleotide Polymorphism Diversity and Threshold of the Outbreak Strains |
| title_full | Whole-Genome Analysis of Bordetella pertussis MT27 Isolates from School-Associated Outbreaks: Single-Nucleotide Polymorphism Diversity and Threshold of the Outbreak Strains |
| title_fullStr | Whole-Genome Analysis of Bordetella pertussis MT27 Isolates from School-Associated Outbreaks: Single-Nucleotide Polymorphism Diversity and Threshold of the Outbreak Strains |
| title_full_unstemmed | Whole-Genome Analysis of Bordetella pertussis MT27 Isolates from School-Associated Outbreaks: Single-Nucleotide Polymorphism Diversity and Threshold of the Outbreak Strains |
| title_short | Whole-Genome Analysis of Bordetella pertussis MT27 Isolates from School-Associated Outbreaks: Single-Nucleotide Polymorphism Diversity and Threshold of the Outbreak Strains |
| title_sort | whole genome analysis of bordetella pertussis mt27 isolates from school associated outbreaks single nucleotide polymorphism diversity and threshold of the outbreak strains |
| topic | Bordetella pertussis outbreak isolate single-nucleotide polymorphism SNP diversity SNP threshold whole-genome sequencing |
| url | https://journals.asm.org/doi/10.1128/spectrum.04065-22 |
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