Unexpected Efficacy of Albumin-Bound Glycerol Monolaurate Against Multidrug-Resistant Bacterial Isolates: A Time-Kill Assay Study

Mona A Alrabiah,1,* Amina A Hassan,2 Murad A Mubaraki,3 Ahmed M Albarrag,4 Mohamed A Dkhil,5 Ali M Somily,4 Denis Delic,6 Taghreed A Hafiz3,* 1Microbiology and Immunology Department, King Khaled University Hospital, Riyadh, 12372, Saudi Arabia; 2National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt; 3Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University, Riyadh, 12372, Saudi Arabia; 4Pathology Department, College of Medicine, King Saud University, Riyadh, 12372, Saudi Arabia; 5Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt; 6Department of Translational Medicine & Clinical Pharmacology, Boehringer Ingelheim Pharma, Biberach, Germany*These authors contributed equally to this workCorrespondence: Taghreed A Hafiz, Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University, Riyadh, 12372, Saudi Arabia, Email [email protected]: The rise of antibiotic resistance is a significant threat to global health, necessitating the exploration of novel antimicrobial agents. Glycerol monolaurate (GML) is known for its antimicrobial properties, primarily against Gram-positive bacteria, with limited evidence of efficacy against Gram-negative pathogens.Methods: This study evaluated the antibacterial activity of GML alone and in combination with human serum albumin (HSA) against clinical isolates of carbapenem-resistant and vancomycin-resistant bacteria using MIC and time-kill assays.Results: Contrary to previous reports, we demonstrate that GML exhibits significant antibacterial activity against Gram-negative bacteria, including strains resistant to conventional antibiotics. It inhibited carbapenem-resistant isolates with MIC values ranging from 25 to 100 μg/mL for E. coli, K. pneumoniae, and E. cloacae and showed bacteriostatic and bactericidal activity. The combination of HSA and GML enhanced this effect, showing potent bactericidal properties across all tested concentrations.Conclusion: Current findings suggest that HSA-bound GML could be developed as a novel broad-spectrum antimicrobial agent targeting multidrug-resistant pathogens. Future research should focus on formulation optimization, in vivo efficacy studies, and preclinical evaluations to determine its therapeutic potential in clinical settings.Keywords: Carbapenem-resistant, human serum albumin, MIC, time-kill assay, clinical isolates