PT  - JOURNAL ARTICLE
AU  - Rodriguez, Priscila
AU  - Abbondante, Serena
AU  - Marshall, Michaela
AU  - Abdelmeseh, Jessica
AU  - Tombola, Francesco
AU  - Pearlman, Eric
TI  - An essential role for the Hv1 voltage-gated proton channel in <em>Pseudomonas aeruginosa</em> corneal infection
AID  - 10.1101/2024.07.15.603631
DP  - 2024 Jan 01
TA  - bioRxiv
PG  - 2024.07.15.603631
4099  - http://biorxiv.org/content/early/2024/07/16/2024.07.15.603631.short
4100  - http://biorxiv.org/content/early/2024/07/16/2024.07.15.603631.full
AB  - Assembly of NADPH oxidase 2 (NOX2) proteins in neutrophils plays an essential role in controlling microbial infections by producing high levels of reactive oxygen species (ROS). In contrast, the role of the Hv1 voltage-gated proton channel that is required for sustained NOX2 activity is less well characterized. We examined the role of Hv1 in a murine model of blinding Pseudomonas aeruginosa corneal infection and found that in contrast to C57BL/6 mice, Hvcn1-/- mice exhibit an impaired ability to kill bacteria and regulate disease severity. In vitro, we used a novel Hv1 Inhibitor Flexible (HIF) to block ROS production by human and murine neutrophils and found that HIF inhibits ROS production in a dose-dependent manner following stimulation with PMA or infection with P. aeruginosa. Collectively, these findings demonstrate an important role for Hv1 on controlling bacterial growth in a clinically relevant bacterial infection model.Competing Interest StatementThe authors have declared no competing interest.