Neisseria gonorrhoeae (NG) in the oropharynx has higher treatment failures and is where antibiotic resistance is generated. Despite this, the dynamics of oral NG infections are not well understood. To address this, we have developed a validated 2D model of NG infection using human oral cells. This model aims to provide data on oral NG infection dynamics to enable the discovery of new antimicrobial treatments for oral NG.
In our model we infected the three different oral cell lines (floor of mouth, gingival and tonsils) with 2 different NG stains: antimicrobial-susceptible (FA1090) and antimicrobial-resistant (WHO-R) and one oral commensal (N oralis) as a negative control. We assessed bacterial invasion and intracellular count following exposure to tetracycline, ciprofloxacin, azithromycin, ceftriaxone, and cefixime at 1, 2, 3x MIC after 30-, 60- and 120-minutes post-infection. Post treatment cells were treated with gentamicin followed by cell lysis. Confocal images were also taken to visualize the internalized bacteria.
Both NG strains infected all the oral cell lines with highest invasion in X cells and lowest in X, whereas the commensal strain caused minimal infection. Gentamicin did not eliminate intracellular NG, but all other antibiotics significantly reduced FA-1090 and WHO-R levels within 30 minutes, with the highest clearance observed at 120 minutes.
Our 2D model is a robust and validated model as our results align with clinical findings of recommended treatments against NG susceptible and resistant strains. With this model, we will study the dynamics of oral NG infection, screen novel antimicrobials to find new treatments for oral NG and to support the development of a 3D model.
This work was supported by the Australian Research Council Industrial Transformation Research Hub to Combat Antimicrobial Resistance (IH190100021).