Plant-Derived Antibacterials Against Multidrug-Resistant Pathogens: From Bactericidal Activity to Synergistic Combinations
Pitard Axel1*, Parizadeh Leila1, Iorfida Ophélie1, Achour Oussama1,2, Sopena Valérie1, Lanneluc Isabelle1, Le Joubioux Florian1, Sirvent Pascal3, Maugard Thierry1, Sablé Sophie1
1UMR CNRS 7266 LIENSs, Université de La Rochelle, 17042 La Rochelle, France;
2Plateforme OpenCampusInnov BioAqtiv, 17000 La Rochelle, France;
3Valbiotis, 17180 Périgny, France;
*E-mail: axel.pitard@univ-lr.fr
Plant-derived bioactive compounds are increasingly recognized as promising alternatives to conventional antibiotics for the management of multidrug-resistant (MDR) bacterial infections. Their broad chemical diversity and multiple mechanisms of action enable them to interfere with several bacterial targets, offering valuable potential to counteract the rise of antimicrobial resistance. This PhD research investigates the antibacterial activity of plant extracts against clinically relevant MDR pathogens, including Staphylococcus aureus (particularly methicillin-resistant strains, MRSA), Pseudomonas aeruginosa, and Acinetobacter baumannii. The study aimed to evaluate their antibacterial and bactericidal efficacy, investigate their molecular and cellular mechanisms of action, and assess their potential as innovative antibiotic-like agents.
A selection of medicinal and aromatic plants traditionally used for the treatment of infectious diseases was investigated. Hydroalcoholic extracts were prepared and initially screened using broth microdilution assays to determine minimum inhibitory concentrations (MICs). Minimum bactericidal concentrations (MBCs) were subsequently determined by subculturing on agar media. Several extracts demonstrated marked antibacterial activity, with MIC values ranging from 0.3125 to 5 mg/mL. These activities were associated with relatively low MBC values and favorable MBC/MIC ratios indicative of bactericidal activity, supporting an antibiotic-like effect against resistant bacterial strains. To further enhance antibacterial efficacy, selected extracts were evaluated in binary combinations against priority MDR pathogens. Combination assays revealed additive effects and, in several cases, significant synergistic interactions, characterized by marked reductions in MIC and/or MBC values compared with those obtained for individual extracts. These findings suggest that combining plant extracts may potentiate antibacterial activity and represent a promising strategy to improve efficacy against MDR bacteria.
Overall, this work identifies several plant extracts and extract combinations displaying significant effects on bacterial growth, favorable interaction profiles, and characterized mechanisms of action. These findings highlight the therapeutic potential of plant-derived bioactive compounds and support their further development as candidates for next-generation antimicrobial therapies targeting multidrug-resistant bacterial infections.
Acknowledgments: The authors thank to ANR, Common laboratory PhytoMar’Innov and Région Nouvelle-Aquitaine PSGAR C3AMR for fundings.
