(Springer Nature, 2017) Euba, Begoña; López López, Nahikari; Rodríguez Arce, Irene; Fernández Calvet, Ariadna; Barberán, Montserrat; Caturla, Nuria; Martí, Sara; Díez Martínez, Roberto; Garmendia García, Juncal; IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua; Gobierno de Navarra / Nafarroako Gobernua; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
The respiratory pathogen nontypeable Haemophilus influenzae (NTHi) is an important cause of acute
exacerbation of chronic obstructive pulmonary disease (AECOPD) that requires efficient treatments.
A previous screening for host genes differentially expressed upon NTHi infection identified sirtuin-1,
which encodes a NAD-dependent deacetylase protective against emphysema and is activated by
resveratrol. This polyphenol concomitantly reduces NTHi viability, therefore highlighting its therapeutic
potential against NTHi infection at the COPD airway. In this study, resveratrol antimicrobial effect
on NTHi was shown to be bacteriostatic and did not induce resistance development in vitro. Analysis
of modulatory properties on the NTHi-host airway epithelial interplay showed that resveratrol
modulates bacterial invasion but not subcellular location, reduces inflammation without targeting
phosphodiesterase 4B gene expression, and dampens β defensin-2 gene expression in infected cells.
Moreover, resveratrol therapeutics against NTHi was evaluated in vivo on mouse respiratory and
zebrafish septicemia infection model systems, showing to decrease NTHi viability in a dose-dependent
manner and reduce airway inflammation upon infection, and to have a significant bacterial clearing
effect without signs of host toxicity, respectively. This study presents resveratrol as a therapeutic of
particular translational significance due to the attractiveness of targeting both infection and overactive
inflammation at the COPD airway.
