TY - JOUR
T1 - Comparative genomic analysis identifies X-factor (haemin)-independent Haemophilus haemolyticus
T2 - a formal re-classification of 'Haemophilus intermedius'
AU - Harris, Tegan M.
AU - Price, Erin P.
AU - Sarovich, Derek S.
AU - Nørskov-Lauritsen, Niels
AU - Beissbarth, Jemima
AU - Chang, Anne B.
AU - Smith-Vaughan, Heidi C.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - The heterogeneous and highly recombinogenic genus Haemophilus comprises several species, some of which are pathogenic to humans. All share an absolute requirement for blood-derived factors during growth. Certain species, such as the pathogen Haemophilus influenzae and the commensal Haemophilus haemolyticus, are thought to require both haemin (X-factor) and nicotinamide adenine dinucleotide (NAD, V-factor), whereas others, such as the informally classified 'Haemophilus intermedius subsp. intermedius', and Haemophilus parainfluenzae, only require V-factor. These differing growth requirements are commonly used for species differentiation, although a number of studies are now revealing issues with this approach. Here, we perform large-scale phylogenomics of 240 Haemophilus spp. genomes, including five 'H. intermedius' genomes generated in the current study, to reveal that strains of the 'H. intermedius' group are in fact haemin-independent H. haemolyticus (hiHh). Closer examination of these hiHh strains revealed that they encode an intact haemin biosynthesis pathway, unlike haemin-dependent H. haemolyticus and H. influenzae, which lack most haemin biosynthesis genes. Our results suggest that the common ancestor of modern-day H. haemolyticus and H. influenzae lost key haemin biosynthesis loci, likely as a consequence of specialized adaptation to otorhinolaryngeal and respiratory niches during their divergence from H. parainfluenzae. Genetic similarity analysis demonstrated that the haemin biosynthesis loci acquired in the hiHh lineage were likely laterally transferred from a H. parainfluenzae ancestor, and that this event probably occurred only once in hiHh. This study further challenges the validity of phenotypic methods for differentiating among Haemophilus species, and highlights the need for whole-genome sequencing for accurate characterization of species within this taxonomically challenging genus.
AB - The heterogeneous and highly recombinogenic genus Haemophilus comprises several species, some of which are pathogenic to humans. All share an absolute requirement for blood-derived factors during growth. Certain species, such as the pathogen Haemophilus influenzae and the commensal Haemophilus haemolyticus, are thought to require both haemin (X-factor) and nicotinamide adenine dinucleotide (NAD, V-factor), whereas others, such as the informally classified 'Haemophilus intermedius subsp. intermedius', and Haemophilus parainfluenzae, only require V-factor. These differing growth requirements are commonly used for species differentiation, although a number of studies are now revealing issues with this approach. Here, we perform large-scale phylogenomics of 240 Haemophilus spp. genomes, including five 'H. intermedius' genomes generated in the current study, to reveal that strains of the 'H. intermedius' group are in fact haemin-independent H. haemolyticus (hiHh). Closer examination of these hiHh strains revealed that they encode an intact haemin biosynthesis pathway, unlike haemin-dependent H. haemolyticus and H. influenzae, which lack most haemin biosynthesis genes. Our results suggest that the common ancestor of modern-day H. haemolyticus and H. influenzae lost key haemin biosynthesis loci, likely as a consequence of specialized adaptation to otorhinolaryngeal and respiratory niches during their divergence from H. parainfluenzae. Genetic similarity analysis demonstrated that the haemin biosynthesis loci acquired in the hiHh lineage were likely laterally transferred from a H. parainfluenzae ancestor, and that this event probably occurred only once in hiHh. This study further challenges the validity of phenotypic methods for differentiating among Haemophilus species, and highlights the need for whole-genome sequencing for accurate characterization of species within this taxonomically challenging genus.
KW - 'Haemophilus intermedius'
KW - comparative genomics
KW - haemin biosynthesis
KW - haemin-independent Haemophilus haemolyticus
KW - Haemophilus haemolyticus
UR - http://www.scopus.com/inward/record.url?scp=85078815523&partnerID=8YFLogxK
U2 - 10.1099/mgen.0.000303
DO - 10.1099/mgen.0.000303
M3 - Article
C2 - 31860436
AN - SCOPUS:85078815523
SN - 2057-5858
VL - 6
SP - 1
EP - 13
JO - Microbial Genomics
JF - Microbial Genomics
IS - 1
ER -
