Klebsiella pneumoniae is a gram-negative bacterium that is known for causing infection innosocomial settings. As reported by the World Health Organization, carbapenem-resistantEnterobacteriaceae, a category that includes K. pneumoniae, are classified as an urgentthreat, and the greatest concern is that these bacterial pathogens may acquire genetictraits that make them resistant towards antibiotics. The last class of antibiotics, carbapenems, are not able to combat these bacterial pathogens, allowing them to clonally expandantibiotic-resistant strains. Most antibiotics target essential pathways of bacterial cells;however, these targets are no longer susceptible to antibiotics. Hence, in our study, we focused on a hypothetical protein in K. pneumoniae that contains a DNA methylation proteindomain, suggesting a new potential site as a drug target. DNA methylation regulates theattenuation of bacterial virulence. We integrated computational-aided drug design by using a bioinformatics approach to perform subtractive genomics, virtual screening, and fingerprint similarity search. We identified a new potential drug, koenimbine, which could bea novel antibiotic.
The continuous rise of antimicrobial resistance (AMR) is a serious concern as it endangers the effectiveness of healthcare interventions that rely on antibiotics in the long run. The increasing resistance of Neisseria gonorrhoeae, the bacteria responsible for causing gonorrhea, to commonly used antimicrobial drugs, is a major concern. This has now become a critical global health crisis. In the coming years, there is a risk of a hidden epidemic caused by the emergence of gonococcal AMR. This will worsen the global situation. Infections caused by N. gonorrhoeae were once considered easily treatable. However, over time, they have become increasingly resistant to commonly used therapeutic medications, such as penicillin, ciprofloxacin, and azithromycin. As a result, this pathogen is developing into a true "superbug," which means that ceftriaxone is now the only available option for initial empirical treatment. Effective management strategies are urgently needed to prevent severe consequences, such as infertility and pelvic inflammatory disease, which can result from delayed intervention. This review provides a thorough analysis of the escalating problem of N. gonorrhoeae, including its pathogenesis, current treatment options, the emergence of drug-resistant mechanisms, and the potential for vaccine development. We aim to provide valuable insights for healthcare practitioners, policymakers, and researchers in their efforts to combat N. gonorrhoeae antibiotic resistance by elucidating the multifaceted aspects of this global challenge.
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.