Background: Klebsiella pneumoniae is a ubiquitous opportunistic pathogen that poses a significant threat to hospitalized patients by causing a wide range of infections. The alarming increase in clinical resistance to all current antibiotics necessitates the urgent identification of novel therapeutic targets and development of effective antimicrobial agents. Materials and Methods: Using pan-genomic analysis of the core protein repertoire of K. pneumoniae, we applied a subtractive proteomics approach to uncover potential drug targets. This has led to the identification of CsgD as a promising candidate. Structural modelling and validation of CsgD were performed. A comprehensive virtual screening of 29,384 natural compounds sourced from Traditional Chinese Medicine (TCM) libraries was performed against CsgD, which yielded three candidates with low binding energies and desirable pharmacodynamic profiles, as validated by Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) prediction.100-nanosecond molecular dynamics simulations were performed to further substantiate their efficacy. Results: Through a rigorous virtual screening process using the TCM database, we identified three compounds with potential antibacterial activity against K. pneumoniae. In particular, mydriatin stands out as a potent CsgD inhibitor, demonstrating a significant inhibitory effect on antibiotic-resistant strains of K. pneumoniae in vitro antibacterial activity evaluation. Conclusion: This study identified mydriatin as a potential therapeutic agent targeting CsgD in K. pneumoniae, offering a promising strategy for the development of novel antimicrobials to combat drug-resistant infections caused by this pathogen. Our results highlight the importance of using natural product libraries and computational methods in the discovery and rational design of novel antibiotics to address the pressing challenges posed by multidrug resistance in K. pneumoniae.

This study focuses on Yersinia pestis, the bacterium responsible for plague, which posed a severe threat to public health in history. Despite the availability of antibiotics treatment, the emergence of antibiotic resistance in this pathogen has increased challenges of controlling the infections and plague outbreaks. The development of new drug targets and therapies is urgently needed. This research aims to identify novel protein targets from 28 Y. pestis strains by the integrative pan-genomic and subtractive genomics approach. Additionally, it seeks to screen out potential safe and effective alternative therapies against these targets via high-throughput virtual screening. Targets should lack homology to human, gut microbiota, and known human 'anti-targets', while should exhibit essentiality for pathogen's survival and virulence, druggability, antibiotic resistance, and broad spectrum across multiple pathogenic bacteria. We identified two promising targets: the aminotransferase class I/class II domain-containing protein and 3-oxoacyl-[acyl-carrier-protein] synthase 2. These proteins were modeled using AlphaFold2, validated through several structural analyses, and were subjected to molecular docking and ADMET analysis. Molecular dynamics simulations determined the stability of the ligand-target complexes, providing potential therapeutic options against Y. pestis.

Infections with drug-resistant bacteria have become one of the greatest public health challenges, and K. pneumoniae is among the top six drug-resistant bacteria. K. pneumoniae often causes nosocomial infections, leading to illnesses such as pneumonia, liver abscesses, soft tissue infections, urinary tract infections, bacteremia, and in some cases death. As the pathogen continues to evolve and its multidrug resistance increases, K. pneumoniae poses a direct threat to humans. Drug resistance in K. pneumoniae may occur due to the formation of biofilms, efflux pumps, and the production of beta-lactamases. In many cases, resistance is further enhanced by enzymatic modification and loss of porins. Drug resistance to K. pneumoniae has led to a decline in the effectiveness of conventional therapies against this pathogen. Therefore, there is an urgent need to accelerate the development of new antibiotics and explore new therapeutic approaches such as antimicrobial peptides, phages, traditional Chinese medicine, immunotherapy, Antimicrobial nanoparticle technology, antisense oligonucleotides and gene editing technologies. In this review, we discuss the mechanisms of drug resistance in K. pneumoniae and compare several new potential therapeutic strategies to overcome drug resistance in the treatment of K. pneumoniae infections.

Klebsiella pneumoniae is an important multidrug-resistant (MDR) pathogen that can cause a range of infections in hospitalized patients. With the growing use of antibiotics, MDR K. pneumoniae is more prevalent, posing additional difficulties and obstacles in clinical therapy. To provide a valuable reference to deeply understand K. pneumoniae, and also to provide the theoretical basis for clinical prevention of such bacteria infections, the antibiotic resistance and mechanism of K. pneumoniae are discussed in this article. We conducted a literature review on antibiotic resistance of K. pneumoniae. We ran a thorough literature search of PubMed, Web of Science, and Scopus, among other databases. We also thoroughly searched the literature listed in the papers. We searched all antibiotic resistance mechanisms and genes of seven important antibiotics used to treat K. pneumoniae infections. Antibiotics such as β-lactams, aminoglycosides, and quinolones are used in the treatment of K. pneumoniae infection. With both chromosomal and plasmid-encoded ARGs, this pathogen has diverse resistance genes. Carbapenem resistance genes, enlarged-spectrum β-lactamase genes, and AmpC genes are the most often β-lactamase resistance genes. K. pneumoniae is a major contributor to antibiotic resistance worldwide. Understanding K. pneumoniae antibiotic resistance mechanisms and molecular characteristics will be important for the design of targeted prevention and novel control strategies against this pathogen.

Purpose: This research traces the history of pharmacy services research in Chinese pharmacies over the past twenty years and attempts to identify key trends and hotspots consistent with global practices. Methodology: From January 2002 to December 2022, we leveraged databases such as CNKI, VIP, and Wanfang and deployed CiteSpace 5.8.R3 to visualize publication trends, authorship, and institutional contributions within the field. Results: Our synthesis highlights critical developments in drug safety monitoring, prescription management, pharmacoeconomics, and public health education and highlights the leadership of respected researchers and institutions. Conclusion: The “Internet+” paradigm is identified as an important catalyst for pharmacy services innovation, with implications that extend beyond China and suggest models for international adaptation and strategy development.

The rapid development of antibiotic resistance in K. pneumonia has led to a major concern. In order to analyze the hotspots and develop trends in this field through visual the analysis, this study used CiteSpace software to summarize the available data in the literature to provide insights. A total of 9366 research articles were retrieved from the Web of Science Core Collection, and the number of published papers is increasing year by year. The country with the most articles was the USA, followed by China and India. The institution with the highest number of publications was LERU. The author with the highest number of articles was Li. The journal with the highest citation rate was Antimicrobial Agents and Chemotherapy. In addition, based on keyword coword analysis and cited literature prominence analysis by CiteSpace, the current research focus in the field was therapy, CRKP, and resistance genes. This paper provides a new quantitative visualization way for the development of the field in the recent ten years. The results show global trends that researchers can use to determine future directions.

Increased glycolysis in tumor cells is associated with increased risk of tumor progression and mortality. Therefore, disruption of glycolysis, one of the main sources of cellular energy supply, can serve as a target for suppressing tumor growth and progression. Of note, hexokinase-2 (HK2) plays vital roles in glucose metabolism. Moreover, the expression of HK2 alters the metabolic phenotype and supports the continuous growth of tumor cells, making it an attractive target for cancer therapy. Quercetin (QUE), a bioactive flavonoid, has a profound anti-tumor effect on hepatocellular carcinoma (HCC), but the precise underlying mechanism of this effect is unclear. In the present study, we reported that QUE inhibited the proliferation of HCC cells that relied on aerobic glycolysis. We further found that QUE could decrease the protein levels of HK2 and suppress the AKT/mTOR pathway in HCC cells. In addition, QUE significantly restrained the growth of HCC xenografts and decreased HK-2 expression in vivo. Taken together, we have revealed that QUE suppresses the progression of HCC by inhibiting HK2-dependentglycolysis, which may have a promising potential to be an effective treatments for HCC, especially for those patients with high HK2 expression.