Phagosomal Acidification Is Required to Kill Streptococcus pneumoniae in a Zebrafish Model

Streptococcus pneumoniae (the pneumococcus) is a major human pathogen causing invasive disease, including community-acquired bacteraemia, and remains leading cause of global mortality. Understanding the role phagocytes in killing bacteria still limited, especially vivo. In this study, we established zebrafish model to study interaction between intravenously administered pneumococci professional such as macrophages neutrophils, unravel bacterial mechanisms employed by these immune cells. Our confirmed key polysaccharide capsule promoting pneumococcal virulence through inhibition phagocytosis. Conversely, show lacking are rapidly internalised macrophages. Low doses encapsulated S. near 100% mortality within 48 hours postinfection (hpi), while 50 times higher unencapsulated easily cleared. Time course analysis vivo numbers reveals that pneumococcus proliferates levels exceeding 105 CFU at time host death, unable grow cleared 20 hpi. Using genetically induced macrophage depletion, an essential for clearance. Additionally, upon phagocytosis macrophages, phagosomes undergo rapid acidification. Genetic chemical vacuolar ATPase (v-ATPase) prevents intracellular induces death indicating phagosomal acidification immunity invading pneumococci. We also our can be used efficacy antimicrobials against Collectively, data confirm larval dissect during infection highlight roles