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Free keywords:
cystic fibrosis; viruses; metagenomics; antibiotic resistance
Abstract:
Microbial communities in the lungs of patients with cystic fibrosis
(CF) and chronic obstructive pulmonary disease (COPD) have been
shown to be spatially heterogeneous. Viral communities may also
vary spatially, leading to localized viral populations and infections.
Here, wecharacterized viral communities frommultiple areas of the
lungs of two patients with late-stage CF using metagenomics, that
is, the explanted lungs froma transplant patient and lungs acquired
postmortem. All regions harbored eukaryotic viruses that may
infect the human host, notably herpesviruses, anelloviruses, and
papillomaviruses. In the highly diseased apical lobes of explant
lungs, viral diversity was extremely low, and only eukaryotic viruses
were present. The absence of phage suggests that CF-associated
microbial biofilms may escape top-down controls by phage predation.
The phages present in other lobes of explant lungs and in all
lobes of postmortem lungs comprised distinct communities, and
encoded genes for clinically important microbial phenotypes,
including small colony variants and antibiotic resistance. Based on
the these observations, we postulate that viral communities in CF
lungs are spatially distinct and contribute to CF pathology by
augmenting the metabolic potential of resident microbes, as well
as by directly damaging lung tissue via carcinomas and herpesviral
outbreaks.
