Learning from -omics strategies applied to uncover Haemophilus influenzae host-pathogen interactions: Current status and perspectives

Abstract

Haemophilus influenzae has contributed to key bacterial genome sequencing hallmarks, as being not only the first bacterium to be genome-sequenced, but also starring the first genome-wide analysis of chromosomes directly transformed with DNA from a divergent genotype, and pioneering Tn-seq methodologies. Over the years, the phenomenal and constantly evolving development of -omic technologies applied to a whole range of biological questions of clinical relevance in the H. influenzae-host interplay, has greatly moved forward our understanding of this human-adapted pathogen, responsible for multiple acute and chronic infections of the respiratory tract. In this way, essential genes, virulence factors, pathoadaptive traits, and multi-layer gene expression regulatory networks with both genomic and epigenomic complexity levels are being elucidated. Likewise, the unstoppable increasing whole genome sequencing information underpinning H. influenzae great genomic plasticity, mainly when referring to non-capsulated strains, poses major challenges to understand the genomic basis of clinically relevant phenotypes and even more, to clearly highlight potential targets of clinical interest for diagnostic, therapeutic or vaccine development. We review here how genomic, transcriptomic, proteomic and metabolomic-based approaches are great contributors to our current understanding of the interactions between H. influenzae and the human airways, and point possible strategies to maximize their usefulness in the context of biomedical research and clinical needs on this human-adapted bacterial pathogen.

Keywords: Airway infection; Genome; Haemophilus influenzae; Metabolome; Methylome; Proteome; Tn-seq; Transcriptome.

Fig. 1

Summarized landscape of –omics contribution to our understanding of the interactions between H. influenzae and the human host. The timeline starts when the first H. influenzae complete genome was sequenced, as a major breakthrough on our understanding of the biology, diversity and evolution of bacteria. We highlight key genomic (labeled in blue), transcriptomic (labeled in grey), metabolomic (labeled in yellow), and Tn-seq screening (labeled in green)-based milestones and contributions over time. Information regarding H. influenzae population structure, genome-wide expression profiling, metabolic capabilities, and genetic screenings keeps growing along the entire timeline (indicated with dotted arrows). SMRT, single-molecule real-time; NTHi, nontypeable Haemophilus influenzae; COPD, chronic obstructive pulmonary disease; dual RNA-seq, dual RNA-sequencing; HITS, high-throughput insertion tracking by deep sequencing; Tn-seq, transposon sequencing; GWAS, genome-wide association studies. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)