O pa+ N eisseria gonorrhoeae exhibits reduced survival in human neutrophils via S rc family kinase‐mediated bacterial trafficking into mature phagolysosomes

Summary During gonorrhoeal infection, there is a heterogeneous population of N eisseria gonorrhoeae ( G c) varied in their expression of opacity‐associated ( O pa) proteins. While O pa proteins are important for bacterial attachment and invasion of epithelial cells, O pa+ G c has a survival defect after exposure to neutrophils. Here, we use constitutively O pa− and O pa D + G c in strain background FA 1090 to show that O pa+ G c is more sensitive to killing inside adherent, chemokine‐treated primary human neutrophils due to increased bacterial residence in mature, degradative phagolysosomes that contain primary and secondary granule antimicrobial contents. Although O pa+ G c stimulates a potent oxidative burst, neutrophil killing of O pa+ G c was instead attributable to non‐oxidative components, particularly neutrophil proteases and the bactericidal/permeability‐increasing protein. Blocking interaction of O pa+ G c with carcinoembryonic antigen‐related cell adhesion molecules ( CEACAMs ) or inhibiting S rc family kinase signalling, which is downstream of CEACAM activation, enhanced the survival of O pa+ G c in neutrophils. S rc family kinase signalling was required for fusion of G c phagosomes with primary granules to generate mature phagolysosomes. Conversely, ectopic activation of S rc family kinases or coinfection with O pa+ G c resulted in decreased survival of O pa− G c in neutrophils. From these results, we conclude that O pa protein expression is an important modulator of G c survival characteristics in neutrophils by influencing phagosome dynamics and thus bacterial exposure to neutrophils’ full antimicrobial arsenal.