A holistic overview of the latest research on the antimicrobial activity and synergy of herbal plant extracts on carbapenem-resistant Escherichia coli and multidrug-resistant clinical isolates is discussed, revealing a glimpse of their potential as next-generation antimicrobials.
Abstract
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.
Background: The global rise of multidrug-resistant (MDR) uropathogens, particularly Escherichia coli and Klebsiella pneumoniae, has narrowed therapeutic options for urinary tract infections (UTIs) and renewed interest in plant-derived antimicrobial adjuvants. Objective: To evaluate the in vitro synergistic activity of three phytochemical extracts pomegranate peel (Punica granatum), garlic (Allium sativum), and green tea (Camellia sinensis) combined with conventional antibiotics against MDR clinical isolates recovered from UTI patients attending Tikrit Teaching Hospital. Methods: Ninety MDR isolates (54 E. coli, 36 K. pneumoniae) were collected, identified, and screened for antimicrobial susceptibility by the Kirby–Bauer disc diffusion method against a 13-agent panel, with MDR classified according to Magiorakos et al., criteria. Minimum inhibitory concentrations (MIC) of ethanolic extracts were determined by broth microdilution, and interactions with ciprofloxacin, ceftazidime, gentamicin, and trimethoprim–sulfamethoxazole were assessed by the checkerboard method, expressed as the fractional inhibitory concentration index (FICI). A time-kill assay verified the most active combination. Results: Isolates showed high resistance to ampicillin (94–98%), amoxicillin–clavulanate (79–86%), and third-generation cephalosporins (72–83%), with lower resistance to meropenem and amikacin. All three extracts showed synergistic or additive interactions with the tested antibiotics; green tea extract combined with ciprofloxacin produced the strongest synergy (mean FICI 0.18–0.24; 100% synergy rate) and an 8–11-fold reduction in antibiotic MIC, followed by pomegranate peel and garlic extracts. Time-kill assays confirmed complete eradication of the test inoculum within 24 hours with the green tea–ciprofloxacin combination, versus partial inhibition with either agent alone. Conclusion: Phytochemical–antibiotic combinations, particularly green tea extract with fluoroquinolones, may restore antibacterial efficacy against MDR uropathogens and merit further in vivo and clinical evaluation.
Sura Mustafa Qasim· SAR Journal of Pathology and...· 0 citations
Background: The rapid emergence of antibiotic resistance in E. coli has outpaced the development of new drugs, creating an urgent demand for novel therapeutic strategies. Methods: We screened ten antibiotics in combination with isochlorogenic acid C (ICAC) against multidrug-resistant (MDR) E. coli. Synergistic effects of antibiotics and ICAC were evaluated by measuring the leakage of alkaline phosphatase (AKP), potassium ions (K+), as well as changes in total protein, and ATP levels. The integrity of bacterial membrane and cell wall was visualized by SEM and CLSM. The underlying mechanisms were elucidated via proteomic analysis and molecular docking. Finally, the protective effect of ICAC in vivo was evaluated using an intraperitoneal infection model in SPF female BALB/c mice. Results: ICAC exerted a specific synergistic effect with ciprofloxacin, significantly enhancing its efficacy. The combination disrupted bacterial membrane and cell wall integrity, increased permeability, and inhibited ATP synthesis. Mechanistically, ICAC may target OmpF and inhibit fatty acid biosynthesis. This interference reduced β-oxidation and the influx of acetyl-CoA into the TCA cycle, thereby impairing bacterial energy metabolism and destabilizing the membrane. In vivo validation using a mouse peritonitis model confirmed that the combination treatment effectively alleviated systemic E. coli infection. Conclusion: ICAC may potentiate the antibacterial activity of ciprofloxacin through targeting of OmpF, which disrupts bacterial membrane integrity and energy metabolism, providing a promising candidate strategy for combating infections caused by the tested antibiotic-resistant E. coli.
Yu-Bin Bai, Xu Chen, Rong-Bin Hu et al.· Biomolecules· 0 citations
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.
S. Ruga, Elisa Matarese, F. Castagna et al.· Antibiotics· 1 citation
Acinetobacter baumannii, a multidrug-resistant Gram-negative bacterium, is increasingly recognized as an oral pathogen. With rising resistance to available antibiotics, plant-derived alternatives are gaining attention. This study aimed to evaluate the antibacterial activity of extracts of Mimusops elengi seed, Aloe barbadensis gel, and root extracts of Cocos nucifera, Areca catechu, and Piper nigrum against A. baumannii. Plant extracts were tested individually as well as in different combinations to evaluate the synergistic activity. Dental plaque samples were collected and cultured in nutrient media, and pure colonies of bacterial isolates were identified based on morphology. Based on the occurrence frequency, the isolated Morphotype A, was used for Anti-Bacterial Susceptibility Testing (ABST) via the disk diffusion method. The identity of the bacterium was confirmed by 16S rRNA gene sequencing. Crude plant extracts were prepared using methanol and subjected to ABST, individually and in combinations (1:1:1 ratio). Two, 0.2 % chlorhexidine containing mouthwashes (Positive) and sterile distilled water (Negative) were used as controls. According to ABST results, A. catechu (13.573 ± 0.0200 mm) and C. nucifera (13.108 ± 0.0366 mm) extracts showed moderate inhibition, while M. elengi showed slightly higher inhibition (14.500± 0.0643 mm). Aloe barbadensis showed the least zone of inhibition (9.017 ± 0.0328 mm), whereas P. nigrum had no effect. The combination of extracts (15.853 ± 0.0288 mm) and chlorhexidine mouthwashes (15.028 ± 0.0413 mm, 15.815 ± 0.0683 mm) also produced comparable inhibition zones, with no statistically significant difference (p > 0.05). The antibacterial activity of the combined extracts did not significantly differ from the individual effects of A. catechu or C. nucifera. Overall, M. elengi seed, A. catechu, C. nucifera root, and A. barbadensis gel extracts exhibited notable antibacterial activity against A. baumannii, individually as well as in combinations, highlighting their effectiveness as plant-based alternatives for combating A. baumannii infections.
Y. R. B. Wickramanayake, T. C. Weeraratne, W. P. P. D. de Silva· Ceylon Journal of Science· 0 citations
Over the past few years, considerable scholarly interest has been directed toward the synergistic application of natural compounds alongside conventional antibiotics to address infections stemming from multidrug-resistant (MDR) pathogens. The primary objective of this research is to investigate the efficacy of baicalin (BA), an extract obtained from Scutellaria baicalensis, when used in conjunction with oxacillin sodium (OXS). Specifically, the study evaluates their combined impact on biofilm formation and toxicity reduction in methicillin-resistant Staphylococcus aureus (MRSA) strain USA300. Furthermore, a murine peritonitis model induced by MRSA USA300 was developed to determine the therapeutic potential of this combination therapy against infection. Experimental data indicate that the co-administration of BA and OXS does not induce hemolysis in vitro. In comparison to treatments involving either BA or OXS alone, the combined regimen significantly enhances the accumulation of intracellular reactive oxygen species (ROS) within MRSA USA300. Additionally, this synergistic approach suppresses the production of extracellular polymeric substances (EPSs), decreases the overall protein content within the biofilm matrix, and impairs the metabolic functions of biofilm cells. The investigation also revealed that the synergistic application of BA and OXS intensifies the suppression of key virulence determinants, specifically lipase activity and staphyloxanthin production, while simultaneously downregulating the transcription of sarA (a global regulator of virulence). These findings substantiate the anti-virulence efficacy of the BA-OXS combination. In a murine model of peritonitis established using MRSA USA300, the healthy mice group, the MRSA USA300 group, the BA group, the OXS group, the combined group of BA and OXS, and the VAN group were set up, with eight mice in each group. The results showed that the combined therapy significantly mitigated body weight reduction, decreased the circulating counts of inflammatory cells, including leukocytes and lymphocytes, and suppressed the secretion of pro-inflammatory mediators such as TNF-α, IL-6, and IL-1β, thereby demonstrating potent anti-inflammatory properties. Furthermore, the co-administration of BA and OXS reduced bacterial burden in the abdominal organs of infected mice and alleviated associated histopathological injuries. Importantly, the treatment regimen exhibited no hepatorenal toxicity in the peritonitis mice, effectively maintaining normal levels. In the plasma of mice suffering from peritonitis, the concentration of malondialdehyde (MDA), a marker of oxidative stress, was reduced, while the activities of catalase (CAT) and superoxide dismutase (SOD) were elevated. This modulation contributes to anti-infective effects. These findings offer a theoretical foundation for subsequent investigations into the synergistic application of natural compounds and conventional antibiotics against MRSA.
ABSTRACT Bacterial resistance to antibiotics represents a critical global health challenge, demanding urgent alternative strategies to manage infections caused by multidrug‐resistant (MDR) pathogens such as Acinetobacter baumannii, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae. A promising approach to address this problem involves the use of combination therapies, in which plant‐derived natural products represent an important reservoir of bioactive compounds with the potential to act as effective adjuvants, restoring or enhancing antibiotic efficacy. In this study, the ethanolic extract of Mouriri elliptica (EME) leaves was investigated for its antimicrobial and synergistic potential. EME showed moderate inhibitory activity against both standard and MDR strains, with the most significant effect against A. baumannii (MIC 78.1–312.5 µg/mL). Synergistic interactions were observed with conventional antibiotics, particularly ciprofloxacin against K. pneumoniae, reducing MIC values up to fifteen‐fold, and with ampicillin against E. coli and S. aureus. The extract also inhibited biofilm formation, with 68% inhibition for E. coli at 500 µg/mL and 72.04% for S. aureus at 250 µg/mL, with atomic force microscopy images corroborating these findings. LC‐MS profiling identified 41 compounds, including chlorogenic acid derivatives, flavonoids, ellagic acid derivatives, and triterpenes. Acute toxicity evaluation in mice at 2000 mg/kg revealed no adverse effects. Collectively, these findings support the potential of M. elliptica as a natural antibacterial adjuvant for enhancing the effectiveness of selected antibiotics against MDR pathogens, warranting further chemical, mechanistic, and in vivo investigation.
T. V. Freire, Ana Carolina de Freitas Marques, Valéria dos Santos Gonçalves et al.· MicrobiologyOpen· 0 citations
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