Clavulanic Acid

This study aimed to determine the prevalence, serovars, virulence gene profiles, antimicrobial resistance patterns, and extended-spectrum β-lactamase (ESBL) genes in Salmonella isolated from broiler chickens in Egypt. In this study, 200 samples were obtained from broiler chickens. Samples were processed using standard bacteriological techniques, and suspected isolates were biochemically identified and molecularly confirmed by PCR targeting the inv A gene. Serotyping was performed according to the Kauffmann–White scheme. Virulence genes ( hil A, stn , spv C, and spi C) and ESBL genes ( blaTEM , blaSHV , and blaCTX −M ) were detected by PCR. Antimicrobial susceptibility testing was carried out following CLSI guidelines. Nineteen isolates (9.5%) were confirmed as Salmonella . Serotyping revealed four serovars: S . Kentucky (52.63%), S . Typhimurium (21.05%), S . Salamae (15.79%), and S . Infantis (10.53%). All isolates carried inv A and hil A, while stn and spi C were present in 84.21% and 73.68% of isolates, respectively, spv C was detected in only one isolate (5.26%). All isolates were resistant to ceftazidime, cefepime, and erythromycin. High resistance rates were also observed against amoxicillin, amoxicillin-clavulanic acid, ciprofloxacin, and doxycycline. Detection of ESBL genes revealed that blaTEM was present in 16 isolates (84.2%), blaCTX−M in 6 isolates (31.6%), and blaSHV in 2 isolates (10.5%). Statistical analyses (Chi-square and Spearman’s correlation tests) further confirmed significant associations between ESBL genes and both phenotypic resistance and virulence determinants, strengthening the validity of our findings. The high prevalence of virulence factors and antimicrobial resistance traits, particularly extensively drug-resistant (XDR) phenotypes and ESBL-encoding genes among Salmonella isolates from poultry, represents a critical public health concern. These findings emphasize the need for continuous molecular surveillance, improved antimicrobial stewardship, and enhanced biosecurity strategies in poultry production in Egypt.

Antimicrobial resistance driven by β-lactamase enzymes, particularly TEM-1 in Escherichia coli, compromises the efficacy of β-lactam antibiotics. This study applied a deep learning-guided pipeline to identify Mangifera indica phytochemicals as potential TEM-1 inhibitors. A neural network trained on 220 compounds achieved a ROC-AUC of 0.81, PR-AUC of 0.85, and Matthews correlation coefficient (MCC) of 0.64, with enrichment factors 1.55 at both 1 % and 5 % thresholds, demonstrating robust predictive ability. Screening of M. indica phytochemicals yielded 25 top-ranked compounds, of which seven satisfied drug-likeness and pharmacokinetic criteria. Docking analysis showed free binding energies ranging from -9.10 to -7.80 kcal·mol⁻¹ , outperforming Tazobactam (-8.07 kcal·mol⁻¹) and clavulanic acid (-6.20 kcal·mol⁻¹). The best-scoring ligands (LTS0215935, LTS0057337, LTS0207894, and LTS0086727) formed extensive hydrogen-bond networks with catalytic residues Ser70, Ser130, Asn132, Ser235, and Arg244. Molecular dynamics (500 ns) confirmed complex stability, with RMSD values between 2.0 and 3.5 Å, reduced residue fluctuations in the SDN and Ω loops, and compact global folds reflected by Rg (26-28 Å). Solvent-accessible surface area analysis revealed tighter packing for LTS0215935 (24.5-26.0 × 10 ³ Ų) compared to Tazobactam (26.5-27.5 × 10 ³ Ų). MM-GBSA calculations ranked LTS0215935 (-47.5 kcal·mol⁻¹) as the strongest binder, followed by LTS0057337 (-43.5 kcal·mol⁻¹), LTS0207894 (-42.6 kcal·mol⁻¹), and LTS0086727 (-43.1 kcal·mol⁻¹), all surpassing Tazobactam (-32.4 kcal·mol⁻¹). Density functional theory (DFT) analysis corroborated these findings, with HOMO-LUMO gaps indicating suitable electronic reactivity and molecular electrostatic potential maps highlighting complementarity with TEM-1 active-site residues. These results nominate M. indica scaffolds, particularly LTS0215935, as promising natural templates for next-generation β-lactamase inhibitors.