Aim This study aimed to test biofilm inhibition activities of each of essential oils (EOs), main compounds of EOs and enzymes against pathogenic Klebsiella pneumoniae. Methods and Results The effect of seven EOs and three enzymes was tested on formation and eradication of K. pneumoniae biofilm. Peppermint oil showed a robust biofilm inhibitory effect, causing inhibition that ranged from 69·2 to 98·2% at 5 μl ml⁻¹. Thyme oil was found to have the best biofilm eradication ability, causing eradication that ranged from 80·1 to 98·0% at 10 μl ml⁻¹. The most effective EOs were analysed by GC/MS, to determine the major chemical constitutes of each oil. Pure menthol was found to cause 75·3–97·5% biofilm inhibition at 2·5 μg ml⁻¹, whereas thymol caused 85·1–97·8% biofilm eradication at 5 μg ml⁻¹. However, moderate inhibition activity was detected for α-amylase and bromelain, while poor activity was detected for β-amylase. Ciprofloxacin combination with thyme oil and thymol was found to enhance antibiotic activity, and affect biofilm cell viability. The observed inhibitory/eradication activity on K. pneumoniae biofilms was confirmed by scanning electron microscopy. Conclusions Thyme and peppermint EOs, and their active components are promising antibiofilm agents alone and/or in combination with ciprofloxacin to inhibit/eradicate biofilms of K. pneumoniae. Significance and Impact of the Study The presented results suggest the potential application of EOs against infections, caused by biofilm-producing K. pneumoniae, to prevent biofilm formation or decrease their resistance threshold. Moreover, the combination of EOs with ciprofloxacin minimizes the antibiotic concentration used and accordingly the potential accompanying toxic side effects.

Purpose: The rise of carbapenem-resistant A. baumannii (CRAB) is considered a public health problem limiting the treatment options. Our current work studied the emergence and mechanisms of colistin-resistance among CRAB isolates in Egypt. Materials and Methods: Seventeen clinically recovered A. baumannii were identified and screened for their antimicrobial susceptibilities using VITEK-2 system. Colistin susceptibility was evaluated using broth microdilution, and characterization of carbapenem/colistin resistance determinants was performed using whole-genome sequencing (Illumina MiSeq). Results: About 52.9% (9/17) were colistin-resistant. PCR results revealed that all isolates carried bla_{OXA-51-like genes}, bla_OXA-23-like was detected in 82.3% (14/17) and bla_NDM in 23.5% (4/17). Two isolates harboured bla_GES-35 and bla_OXA-23. Furthermore, genome analysis of seven isolates revealed six belonged to international clone 2 (IC2) while the remaining isolate was a singleton (ST158), representing a clone circulating in Mediterranean/Middle Eastern countries. Conclusion: The emergence and high incidence of colistin-resistance among CRAB clinical isolates in Egypt are alarming because it further limits therapy options and requires prudent antimicrobial stewardship and stringent infection control measures. Whole-genome sequence analyses suggest that the resistance to colistin was associated with multiple mutations in the pmrCAB genes. The high incidence of the high-risk lineage IC2 harbouring bla_OXA-23-like as well as bla_NDM is also of concern.

This study aims to evaluate the prevalence of multidrug-resistant (MDR) and biofilm-forming pathogens from animal source compared to clinical ones. In addition, to assess the antibacterial and antibiofilm activity of silver nanoparticles (AgNPs) alone and/or mixed with vancomycin. Out of 62 bacterial isolates from animal respiratory tract infection (RTI), 50.00% were defined as MDR, while among human ones, 44.00% were MDR. The bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pneumoniae were the predominant isolated bacteria from both animal and human origin with frequency percentage of 50.00, 22.32, and 18.75, respectively. Among Staph. aureus strains, mecA gene was detected in 60.00% and 61.54% of animal and human isolates, respectively, while mec _ALGA251 (mecC) gene was detected in 13.33% and 15.38% of animal and human isolates, respectively. Biofilm formation ability among animal isolates was 83.87%, while among human ones was 86.00%. AgNPs were effective in inhibiting planktonic cells with minimal inhibitory concentration (MIC) values (0.625–10 μg/mL), as well as eradicating biofilm with minimal biofilm eradication concentration values (1.25–10 μg/mL). Noticeable low MIC of AgNPs was required for the isolates from animal source (0.625–5 μg/mL) compared to clinical ones (0.625–10 μg/mL). Remarkable reduction in AgNP effective concentration was observed after combination with 1/4 MIC of vancomycin with minimum recorded concentration of 0.08 μg/mL. In conclusion, the prevalence of MDR among RT pathogens was recorded with high ability to produce biofilm and virulence factors from both animal and human pathogens. AgNPs showed strong antibacterial and antibiofilm activity alone and mixed with vancomycin, with up to fourfold reduction of AgNP inhibitory dose.

DNA gyrase and topoisomerase IV are proven to be validated targets in the design of novel antibacterial drugs. In this study, we report the antibacterial evaluation and molecular docking studies of previously synthesized two series of cyclic diphenylphosphonates (1a–e and 2a–e) as DNA gyrase inhibitors. The synthesized compounds were screened for their activity (antibacterial and DNA gyrase inhibition) against ciprofloxacin-resistant E.coli and Klebsiella pneumoniae clinical isolates having mutations (deletion and substitution) in QRDR region of DNA gyrase. The target compound (2a) that exhibited the most potent activity against ciprofloxacin Gram-negative clinical isolates was selected to screen its inhibitory activity against DNA gyrase displayed IC₅₀ of 12.03 µM. In addition, a docking study was performed with inhibitor (2a), to illustrate its binding mode in the active site of DNA gyrase and the results were compatible with the observed inhibitory potency. Furthermore, the docking study revealed that the binding of inhibitor (2a) to DNA gyrase is mediated and modulated by divalent Mg²⁺ at good binding energy (–9.08 Kcal/mol). Moreover, structure-activity relationships (SARs) demonstrated that the combination of hydrazinyl moiety in conjunction with the cyclic diphenylphosphonate based scaffold resulted in an optimized molecule that inhibited the bacterial DNA gyrase by its detectable effect in vitro on gyrase-catalyzed DNA supercoiling activity.

Helicobacter pylori infection is one of the most common gastric pathogens; however, the molecular mechanisms driving its progression to gastric cancer remain poorly understood. This study aimed to identify the key transcriptomic drivers and therapeutic targets of H. pylori–associated gastric cancer through an integrative transcriptomic analysis. This analysis integrates microarray and RNA-seq datasets to identify significant differentially expressed genes (DEGs) involved in the progression of H. pylori–associated gastric cancer. In addition to independent analyses, data were integrated using ComBat to detect consistent expression patterns of hub genes. This approach revealed distinct clustering patterns and stage-specific transcriptional changes in common DEGs across disease progression, including H. pylori infection, gastritis, atrophy, and gastric cancer. Genes such as TPX2, MKI67, EXO1, and CTHRC1 exhibited progressive upregulation from infection to cancer, highlighting involvement in cell cycle regulation, DNA repair, and extracellular matrix remodeling. These findings provide insights into molecular shifts linking inflammation-driven infection to malignancy. Furthermore, network analysis identified hub genes, including CXCL1, CCL20, IL12B, and STAT4, which are enriched in immune pathways such as chemotaxis, leukocyte migration, and cytokine signaling. This emphasizes their role in immune dysregulation and tumor development. Expression profiling demonstrated the upregulation of hub genes in gastric cancer and stage-specific changes correlating with disease progression. Finally, drug–gene interaction analysis identified therapeutic opportunities, with hub genes interacting with approved drugs like abatacept and zoledronic acid, as well as developmental drugs such as adjuvant and relapladib. These findings highlight the key role of these hub genes as biomarkers and therapeutic targets, providing a foundation for advancing precision medicine in H. pylori–associated gastric cancer. Overall, this study paves the way for advancing precision medicine in H. pylori–associated gastric cancer by providing insights into the development of early detection biomarkers, risk stratification, and targeted therapies. This supports the clinical translation of precision medicine strategies in H. pylori–associated gastric cancer.