Molecular mechanisms of formation of drug resistance in Neisseria gonorrhoeae: History and prospects

Abstract

Neisseria gonorrhoeae (gonococcus) is a strict human pathogen that causes gonorrhea—an infectious disease the origin of which dates back more than 2000 years. Due to the unique plasticity of their genetic material, these bacteria have acquired the capacity to adapt to the host immune system and cause repeated infections, as well as withstand antimicrobials. Since the 1930s, against the background of the introduction of chemical antibiotic therapy, gonococcus has developed resistance to almost all drugs used in the treatment of gonorrhea. It is important to note that the known resistance determinants of N. gonorrhoeae are located both on the plasmid and in the chromosome and were acquired through horizontal gene transfer and spontaneous and recombination mutagenesis. Unfortunately, after the introduction of each new antibiotic in the scheme of gonorrhea treatment, gonococcus became resistant in about two decades and replaced a sensitive bacterial population. Currently, ceftriaxone is the last remaining antibiotic for first-line treatment of gonorrhea. However, the first gonococcus displaying high-level resistance to this drug was isolated in Japan a few years ago. In other words, in the near future, gonorrhea may become untreatable. The present review considers and discusses the chronology of the replacement of antigonorrhea drugs (antibiotics), the evolution of the formation of gonococcal resistance, and future prospects.