RESUMEN
Targeted drug delivery maximizes the chance to combat infection caused by drug-resistant pathogens. Herein, lectin-fortified cationic copper sulfide (cCuS) nanoparticles were suggested for targeted adhesion to bacterial membranes and to enforce bacterial death. Jacalin, a lectin from jackfruit seed, was conjugated to fluorescein isothiocyanate (FITC), and its ability to recognize bacterial cell surface glycans was demonstrated. Jacalin formed a noncovalent complex with cCuS, which was investigated by fluorescence quenching measurements. The data revealed that jacalin-cCuS (JcCuS) had a good affinity with an association constant K a of 2.27 (± 0.28) × 104 M-1. The resultant JcCuS complex displayed excellent anti-infective activity against carbapenem-resistant Acinetobacter baumannii (CRAB). The minimum inhibitory concentration (MIC) of cCuS was 62.5 µM, which was 2-fold lower than that of the broad-spectrum antibiotic ciprofloxacin. Interestingly, the MIC of JcCuS was reduced to 15.63 µM, which was attributed to jacalin fortification. The mechanistic study unveiled that JcCuS affected the membrane integrity, depolarized the inner membrane, and produced excess reactive oxygen species to combat CRAB at a lower concentration compared to cCuS. A. baumannii formed a biofilm more readily, which played a critical role in pathogenesis and resistance in clinical settings. JcCuS (3.91 µM) displayed stronger antibiofilm activity without affecting the metabolic viability of CRAB. Microscopy analyses confirmed the inhibition of biofilm formation and disruption of the mature biofilm upon treatment with JcCuS. Furthermore, JcCuS hindered pellicle formation and inhibited the biofilm-associated virulence factor of CRAB such as exopolysaccharide, cell surface hydrophobicity, swarming, and twitching mobility. The anti-infective potential of JcCuS was demonstrated by rescuing CRAB-infected zebrafish. The reduction in pathogen proliferation in muscle tissues was observed in the treated group, and the fish recovered from the infection and was restored to normal life within 12 h. The findings illustrate that lectin fortification offers a unique advantage in enhancing the therapeutic potential of antimicrobials against human pathogens of critical priority worldwide.
RESUMEN
AIM: Polymicrobial biofilm encasing cross-kingdom micro-organisms are apparent in medicine, which imposes serious resistance to conventional antimicrobial treatment. The objective of the study was to explore Butea monosperma seed lectin (BMSL) conjugated antimicrobial lipid, 2-((N-[2-hydroxyethyl]palmitamido)methyl)-1-methylpyridin-1-ium iodide (cN16E) to inhibit mixed-species biofilm of uropathogenic Escherichia coli-Candida albicans. METHODS AND RESULTS: Antimicrobial activity and antibiofilm of cN16E and cN16E-BMSL conjugate (BcN16E) were analysed against single- and mixed microbial cultures. The minimum inhibitory concentration (MIC) indicates that the MIC of cN16E-BMSL conjugate (BcN16E) against cohabiting UPEC-C. albicans was eightfold lower than the cN16E. BcN16E affects membrane integrity to elicit antimicrobial activity. BcN16E inhibits the dual-species biofilm even with 16 times lower MIC of cN16E. BcN16E impairs the biofilm-associated virulence factors which include extracellular polysaccharides, cell surface hydrophobicity, swimming, swarming motilities, hyphal filamentous morphology, curli formation and haemolysin activity. As a proof of concept, we demonstrated BcN16E ability to inhibit dual-species biofilm formation on a urinary catheter. CONCLUSION: The study revealed that the BcN16E is better than cN16E in impairing biofilm-associated virulence factors and exerting antimicrobial activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings emphasize that phytolectin has the potential to enhance the anti-virulence strategies of antimicrobials against cross-kingdom biofilm-related infections.
