In Vitro Evaluation of Tellurium-Based AS101 Compound against Neisseria gonorrhoeae Infectivity

Neisseria gonorrhoeae (GC) is a obligate human pathogen responsible for gonorrhea, one of the most common sexually transmitted infections. The yearly increased multidrug resistance in GC has led to treatment failure clinically, suggesting an urgent need for novel therapy to combat this global health issue. AS101 [ammonium trichloro(dioxoethylene-O,O '-)tellurate], a tellurium-based compound previously used as an immunomodulatory agent, was found to have antimicrobial effects against Klebsiella pneumoniae via a high-throughput drug screening and showed antibacterial activity against Acinetobacter spp. This study aimed to evaluate the in vitro anti-gonococcal activity of AS101, including its antimicrobial activity, biofilm and infectivity inhibition, and potential underlying mechanisms. The agar-dilution-based MIC was used. The inhibition of GC microcolony formation and continual growth by AS101 was assessed by microscopy. The effect of AS101 on GC infectivity was evaluated by infecting endocervical ME180 and colorectal T84 epithelial cell lines. The mode of action was evaluated by a time-killing curve, transmission electron microscopy (TEM), and the level of reactive oxygen species (ROS). The MICs of MS11 and WHO GC isolates were both found to be 0.05 mu g/mL. The biofilm formation, continual growth, and infectivity of two epithelial cell lines were significantly decreased with AS101 treatment. The time-kill curve, similar to that of azithromycin, suggested that AS101 is a bacteriostatic antimicrobial. However, TEM and ROS levels implied a mode of action different from that of azithromycin. Our findings highlighted the robust anti-gonococcal activities of AS101, which potentiates its use as a future antimicrobial for GC.IMPORTANCE Neisseria gonorrhoeae is an obligate human pathogen responsible for gonorrhea, one of the most common sexually transmitted infections. The yearly increased multidrug resistance in GC has led to treatment failure clinically, suggesting an urgent need for novel therapy to combat the global health issue. This study aimed to evaluate the in vitro anti-gonococcal activity of a previous immunomodulatory agent, AS101, and its underlying mechanisms. Here, we report that AS101 possesses remarkable anti-gonococcal activity. These findings supported further studies on in vivo experiments and formulations for the clinical application of AS101 as an anti-gonococcal agent. Neisseria gonorrhoeae is an obligate human pathogen responsible for gonorrhea, one of the most common sexually transmitted infections. The yearly increased multidrug resistance in GC has led to treatment failure clinically, suggesting an urgent need for novel therapy to combat the global health issue.