Bacterial acidification as a new virulence mechanism for immune activation and barrier failure via mitochondrial dysfunction
(Hocke / Hippenstiel / Antelmann)
The strict pH regulation is crucial for tissue homeostasis and an adequate immune response. We hypothesize that in pneumoniae the bacterial, fermentative energy metabolism leads to acidification in the alveolar microenvironment, thereby functioning as a virulence mechanism with impact on alveolar innate immune- and barrier function.
We aim to
(i) study the regulation of acidic fermentation endproducts of pneumococci under in vitro conditions and in human lung tissue,
(ii) elucidate the influence of bacterial acidification on pathophysiological mechanisms in pneumonia and
(iii) delineate the molecular mechanisms, how low pH triggers the cellular stress response and might involve mitochondrial pathways.