Box: Future research questions on the pathogenesis and role ofNTHi infections in pediatric chronic suppurative lung disease
Can animal models replicate the complexity of NTHi infection in CSLD?
What are the important interactions between NTHi and the host microbiome?
What role do cilia play in NTHi host-pathogen interactions?
How long do NHTi survive within cells and in intercellular spaces?
How long do NTHi strains survive in the lungs? Are they replaced or constantly changing as a result of intraspecies transformation and recombination of genes from the supragenome?
What are the critical functions of host-pathogen cross-talk that allowNTHi to evade or manipulate host defences?
What part does NETosis have in the pathogenesis of CSLD?
What is the role of NTHi biofilms in progressing CSLD and how might this be overcome by increasing susceptibility to host defences and antimicrobial agents?
What are the regulatory mechanisms controlling a relatively small number of multi-functional proteins that allow NTHi to adapt to environmental changes?
What is the nature, timing and frequency of antigenic, epigenetic and phase variation in lung NTHi isolates?
What are the critical phase-variable genes for establishing NTHilung infection and how they might be important targets for vaccine candidates?
Can NTHi virulence be manipulated by small molecules targeting the quorum sensing system?
What are the mechanisms of antimicrobial resistance in biofilms and where is the reservoir of antibiotic resistant genes?
What impacts do CFTR modulators have upon NTHi infection in CF patients?
What are the host mechanisms of protective immunity?
Will multi-valent vaccines containing highly conserved surface antigens, including antigens under phase-variable control expressed during critical periods of establishing infection overcome the challenges ofNTHi genetic heterogeneity and protect against NTHiinfection?
CF: cystic fibrosis, CFTR: cystic fibrosis transmembrane conductance regulator, CSLD: chronic suppurative lung disease, NTHi , nontypeable Haemophilus influenzae.