Antibiotic resistance in Neisseria gonorrhoeae: broad-spectrum drug target identification using subtractive genomics

Abstract

Neisseria gonorrhoeae is a Gram-negative aerobic diplococcus bacterium that primarily causes sexually transmitted infections through direct human sexual contact. It is a major public health threat due to its impact on reproductive health, the widespread presence of antimicrobial resistance, and the lack of a vaccine. In this study, we used a bioinformatics approach and performed subtractive genomic methods to identify potential drug targets against the core proteome of N. gonorrhoeae (12 strains). In total, 12,300 protein sequences were retrieved, and paralogous proteins were removed using CD-HIT. The remaining sequences were analyzed for non-homology against the human proteome and gut microbiota, and screened for broad-spectrum analysis, druggability, and anti-target analysis. The proteins were also characterized for unique interactions between the host and pathogen through metabolic pathway analysis. Based on the subtractive genomic approach and subcellular localization, we identified one cytoplasmic protein, 2Fe-2S iron-sulfur cluster binding domain-containing protein (NGFG RS03485), as a potential drug target. This protein could be further exploited for drug development to create new medications and therapeutic agents for the treatment of N. gonorrhoeae infections.

Similarity of drug targets to human microbiome metaproteome promotes pharmacological promiscuity

“…In all cases, the drug should be highly specific to one or specific targets in order to minimize off-target effects[15]. Checking the homology of the drug target to the human proteome is crucial to ensure that the functions of essential human proteins are not modulated[16]. Additional considerations in drug target selection may further enhance the success and safety of drug screening campaigns.…”