Development and implementation of a core genome multilocus sequence typing scheme for Haemophilus influenzae

Made Ananda Krisna, Keith A. Jolley, William Monteith, Alexandra Boubour, Raph L. Hamers, Angela B. Brueggemann, Odile B. Harrison, Martin C.J. Maiden

Research output: Contribution to journalArticlepeer-review

Abstract

Haemophilus influenzae is part of the human nasopharyngeal microbiota and a pathogen causing invasive disease. The extensive genetic diversity observed in H. influenzae necessitates discriminatory analytical approaches to evaluate its population structure. This study developed a core genome multilocus sequence typing (cgMLST) scheme for H. influenzae using pangenome analysis tools and validated the cgMLST scheme using datasets consisting of complete reference genomes (N = 14) and high-quality draft H. influenzae genomes (N = 2297). The draft genome dataset was divided into a development dataset (N = 921) and a validation dataset (N = 1376). The development dataset was used to identify potential core genes, and the validation dataset was used to refine the final core gene list to ensure the reliability of the proposed cgMLST scheme. Functional classifications were made for all the resulting core genes. Phylogenetic analyses were performed using both allelic profiles and nucleotide sequence alignments of the core genome to test congruence, as assessed by Spearman's correlation and ordinary least square linear regression tests. Preliminary analyses using the development dataset identified 1067 core genes, which were refined to 1037 with the validation dataset. More than 70% of core genes were predicted to encode proteins essential for metabolism or genetic information processing. Phylogenetic and statistical analyses indicated that the core genome allelic profile accurately represented phylogenetic relatedness among the isolates (R2 = 0.945). We used this cgMLST scheme to define a high-resolution population structure for H. influenzae, which enhances the genomic analysis of this clinically relevant human pathogen.

Original languageEnglish
Article number001281
JournalMicrobial Genomics
Volume10
Issue number8
Early online date1 Aug 2024
DOIs
Publication statusPublished - 31 Aug 2024

Funding

This study was funded by a Wellcome Trust Biomedical Resource Grant to M.J.C.M., A.B.B. and K.A.J. (grant number 218205/Z/19/Z) and a National Institute for Health and Care Research (NIHR) Grant called MEVacP to M.J.C.M., A.B.B. and O.B.H. Studentship for M.A.K. was funded by the Ministry of Education Indonesia in collaboration with the Medical Science Division, University of Oxford.

FundersFunder number
National Institute for Health and Care Research
Ministry of Education Indonesia
The Wellcome Trust218205/Z/19/Z

Keywords

  • cgMLST
  • core genome
  • Haemophilus influenzae
  • population genetics
  • typing scheme

ASJC Scopus subject areas

  • Epidemiology
  • Microbiology
  • Molecular Biology
  • Genetics

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