Plasmid-mediated multidrug resistance and the antibacterial potential of plant seed proteins

Plant-Derived Compounds as Antibiotic Adjuvants Against Drug-Resistant ESKAPE Pathogens: Mechanisms of Action, Synergistic Strategies, and Translational Challenges

Background/Objectives: Antimicrobial resistance among ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens has become a major global health threat, significantly reducing the effectiveness of conventional antibiotics. Plant-derived compounds have emerged as promising antibiotic adjuvants capable of restoring antibiotic activity through multiple resistance-modulating mechanisms. This review aims to critically evaluate the current evidence regarding phytochemicals that enhance antibiotic efficacy against drug-resistant ESKAPE pathogens. Methods: Relevant studies investigating plant-derived compounds with antibiotic adjuvant activity against ESKAPE pathogens were identified and critically analyzed. Particular attention was given to mechanisms of action, synergistic interactions with conventional antibiotics, structure–activity relationships, and translational evidence from in vivo studies. Results: Numerous phytochemicals have demonstrated the ability to potentiate antibiotic activity through efflux pump inhibition, biofilm disruption, membrane permeabilization, and quorum sensing interference. For instance, the flavonoid quercetin inhibits the NorA efflux pump in Staphylococcus aureus, restoring ciprofloxacin susceptibility, while the sulfur-containing compound ajoene from garlic disrupts quorum sensing in Pseudomonas aeruginosa, sensitizing biofilms to tobramycin. Although several compounds exhibit promising synergistic effects in vitro, significant barriers remain regarding bioavailability, standardization, pharmacokinetics, and clinical translation. Conclusions: Plant-derived antibiotic adjuvants represent a promising strategy to combat multidrug-resistant ESKAPE pathogens. However, greater emphasis on translational research, standardized methodologies, and clinically relevant experimental models is required to facilitate their development toward therapeutic applications.

Exploring the Inhibitory Effects of Plant Phytoalexins on Escherichia coli: A Genetic Study of Bacterial Resistance Interactions and Gene Expression Associated with Defense Response

Background: The emergence of multidrug-resistant Escherichia coli (MDR) is a major public health threat, necessitating the search for novel antibiotic alternatives capable of inhibiting bacterial growth and biofilm formation, as well as modifying resistance mechanisms. The growing interest in plant phytoalexins stems from their diverse spectrum of biological activities and antimicrobial properties. Aim: This study aimed to evaluate the anti-biofilm and antibacterial activity of resveratrol and naringenin against MDR E. coli isolates, their effect on the gene expression levels of marA and acrB, and the relationship between gene expression, biofilm formation, and antibiotic resistance. Materials and Methods: Twenty clinical MDR E. coli isolates were identified using conventional microbiological and biochemical methods, with molecular confirmation where required. Antibacterial activity was assessed using a broth microdilution assay and growth inhibition analysis, while biofilm formation was measured using a crystal violet microplate method. Relative gene expression was assessed using quantitative real-time polymerase chain reaction (qRT-PCR) according to the 2ΔΔCt method, with recA used as a reference gene. Statistical analyses were performed using one-way analysis of variance (ANOVA), the chi- square test, and Pearson's correlation test, with p < 0.05 considered statistically significant. Results: Over 90% of the strains exhibited resistance to ampicillin and cefotaxime, while resistance rates to ciprofloxacin and tetracycline exceeded 70%. Resveratrol exhibited greater antibacterial activity than naringin, with a significant reduction in bacterial growth (OD₆₀₀ = 0.48 ± 0.04 vs. 0.61 ± 0.03) and more potent, concentration-dependent inhibition of biofilm formation (68% vs. 54%). Gene expression analysis: All compounds affected the gene expression of two resistance-associated genes, marA and acrB. A general correlation (χ² = 24.7, p = 0.002) was found between resistance genes and apparent resistance. Correlation analysis also indicated a positive relationship between gene expression and biofilm formation (r = 0.78, p < 0.001) and minimum inhibitory concentration (MIC) values ​​(r = 0.41, p < 0.05). Results: qPCR results showed significant differences in buvirdin biosynthesis genes between non-biofilm-forming and biofilm-forming samples. The expression of two genes was significantly higher in all six bioflux strains compared to non-biofilm-forming samples (p ≤ 0.0388). Conclusion: The results show that both resveratrol and naringenin possess antibacterial and anti-biofilm activity against multidrug-resistant E. coli (MDR-EC), with resveratrol exhibiting superior overall activity. The modulation of resistance-associated gene expression and the emerging correlations between gene expression, biofilm formation, and antibiotic resistance suggest that certain plant phytoalexins, particularly resveratrol, may be promising candidates for treating MDR-EC infections.

Antibacterial activity and mechanism of a crab-derived i-type lysozyme against multidrug-resistant Vibrio alginolyticus.

The emergence and rapid spread of multidrug-resistant bacteria in aquaculture environments threatens the healthy development of the aquaculture industry and public health, driving demand for novel antimicrobial agents as alternatives to antibiotics. Marine animals harbor a diverse array of antimicrobial peptides, which exhibit great promise in addressing antibiotic resistance. In this work, the antimicrobial activity and mechanism of a crab-derived i-type lysozyme against multidrug-resistant Vibrio alginolyticus were investigated. The recombinant protein His-Ptlys-i (His-Ptlys-i) could bind to diverse bacteria and pathogen-associated molecular patterns (PAMPs), and displayed antibacterial and agglutinative activities against V. alginolyticus, V. parahaemolyticus, and Staphylococcus aureus. His-Ptlys-i exhibited synergistic/additive inhibitory effects against the multidrug-resistant V. alginolyticus DS016 when combined with tetracycline and fluoroquinolone antibiotics.‌ Transcriptome analysis indicated that His-Ptlys-i suppressed antibiotic resistance genes expression and inhibited multiple pathways, particularly branched-chain amino acid degradation, in V. alginolyticus DS016. Simultaneously, V. alginolyticus DS016 activates the expression of multiple ABC transporters involved in nutrient acquisition to counteract His-Ptlys-i-induced stress. His-Ptlys-i displayed promising antimicrobial activity against multidrug-resistant V. alginolyticus, indicating its potential as a candidate for novel agents combating multidrug-resistant bacteria and addressing the global challenge of antibiotic resistance.

Phage and CRISPR based precision antimicrobials: a dual strategy against multidrug-resistant bacteria

This review critically examines bacteriophage-based antimicrobials, CRISPR-Cas therapeutic systems, and their emerging integration as CRISPR-armed phages, highlighting their comparative advantages, current limitations, and future potential as promising targeted antimicrobial approach platforms requiring further clinical validation.

Pan-genome analysis reveals the triangle mechanisms of antibiotic resistance, pathogenicity, and biofilm formation in Enterococcus faecalis

Synergistic Effects of Selected Herbal Plant Extracts with Antibiotics Against Carbapenem-Resistant Escherichia Coli: A Systematic Review

Background: The rapid emergence of carbapenem-resistant Escherichia coli (CREC) infections is a major threat to global public health, prompting the search for alternative therapeutic options. In this review, the latest research on the antimicrobial activity and synergy of herbal plant extracts on carbapenem-resistant Escherichia coli (CREC) and multidrug-resistant (MDR) clinical isolates is discussed. Key findings point to the capacity of equol, naringenin, and tetrandrine to reinstate the effectiveness of conventional antibiotics, including carbapenems and colistin. Furthermore, the mechanisms of action include the disruption of cell wall and membrane integrity, the inhibition of efflux pump activity, and the downregulation of resistance genes, including carbapenemases and mcr-1. Synergistic interactions, indicated by a Fractional Inhibitory Concentration (FIC) index of less than 0.5, reveal the potential of plant-derived compounds as effective adjuvants. Although in vivo studies in murine models indicate a positive outcome in terms of reduced bacterial loads, translation to the clinic is hindered by a lack of human studies and standardized extraction methodologies. This report presents a holistic overview of these plant-derived approaches, revealing a glimpse of their potential as next-generation antimicrobials.