Abstract

Aggregatibacter and Haemophilus species are relevant human commensals and opportunistic pathogens. Consequently, their bacteriophages may have significant impact on human microbial ecology and pathologies. Our aim was to reveal the prevalence and diversity of bacteriophages infecting Aggregatibacter and Haemophilus species that colonize the human body. Genome mining with comparative genomics, screening of clinical isolates, and profiling of metagenomes allowed characterization of 346 phages grouped in 52 clusters and 18 superclusters. Less than 10% of the identified phage clusters were represented by previously characterized phages. Prophage diversity patterns varied significantly for different phage types, host clades, and environmental niches. A more diverse phage community lysogenizes Haemophilus influenzae and Haemophilus parainfluenzae strains than Aggregatibacter actinomycetemcomitans and “Haemophilus ducreyi”. Co-infections occurred more often in “H. ducreyi”. Phages from Aggregatibacter actinomycetemcomitans preferably lysogenized strains of specific serotype. Prophage patterns shared by subspecies clades of different bacterial species suggest similar ecoevolutionary drivers. Changes in frequencies of DNA uptake signal sequences and guanine–cytosine content reflect phage-host long-term coevolution. Aggregatibacter and Haemophilus phages were prevalent at multiple oral sites. Together, these findings should help exploring the ecoevolutionary forces shaping virus-host interactions in the human microbiome. Putative lytic phages, especially phiKZ-like, may provide new therapeutic options.

Highlights

  • Supplementary information The online version of this article contains supplementary material, which is available to authorized users.Department of Prosthetic Dentistry and Biomedical Materials Science, Hannover Medical School (MHH), Hannover, GermanyLower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover, GermanyCluster of Excellence RESIST (EXC 2155), Hannover, Germany 4 Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark 5 Research Core Unit Electron Microscopy, Hannover MedicalSchool (MHH), Hannover, Germany 6 Cluster of Excellence REBIRTH (EXC 62), Hannover, GermanyAggregatibacter and Haemophilus species of the family Pasteurellaceae encompass commensals and pathogens of considerable ecological and medical importance [1]

  • 828 phage-like elements were discovered, 258 of which were predicted to be intact, coding for at least 40 open reading frames (ORFs), and not duplicated within the dataset—hereafter referred to as “prophages” (Fig. S1b; Table S2). We chose this ORF number cutoff based on results of alignments and clustering where obviously truncated prophage sequences formed separate groups

  • Because of the unequal distribution of available genomes, we focused on four well-represented species, i.e., A. actinomycetemcomitans, “H. ducreyi”, H. influenzae, and H. parainfluenzae as well as the subspecies clades of the first three species

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Summary

Introduction

Cluster of Excellence RESIST (EXC 2155), Hannover, Germany 4 Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark 5 Research Core Unit Electron Microscopy, Hannover Medical. Aggregatibacter and Haemophilus species of the family Pasteurellaceae encompass commensals and pathogens of considerable ecological and medical importance [1]. They dominate mucosal surfaces in the oral cavity and pharynx as well as contributing to dental biofilm development [2,3,4,5]. Haemophilus influenzae is the most important human opportunistic pathogen among Pasteurellaceae species [1]. “Haemophilus ducreyi” is the cause of chancroid, a sexually transmitted disease characterized by genital ulcerations, and cutaneous ulcers in children [1].

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