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The emergence of extended- spectrum β-lactamase (ESBL) is the underlying cause of growing antibiotic resistance among Gram-negative bacteria to β-lactam antibiotics. We recently reported the discovery of honey glycoproteins (glps) that exhibited a rapid, concentration-dependent antibacterial activity against both Gram-positive  Bacillus subtilis  and Gram-negative  Escherichia coli  that resembled action of cell wall-active β-lactam drugs. Glps showed sequence identity with the Major Royal Jelly Protein 1 (MRJP1) precursor that harbors three antimicrobial peptides: Jelleins 1, 2, and 4. Here, we used semi-quantitative radial diffusion assay and broth microdilution assay to evaluate susceptibility of a number of multi-drug resistant (MDR) clinical isolates to the MRJP1-contaning honey glycoproteins. The MDR bacterial strains comprised three methicillin-resistant  Staphylococcus aureus  (MRSA), four  Pseudomonas aeruginosa , two  Klebsiella pneumoniae , two vancomycin-resistant  Enterococci  (VRE), and five ESBL identified as one  Proteus mirabilis , three  E. coli , and one  E. coli  NDM. Their resistance to different classes of antibiotics was confirmed using automated system Vitek 2. MDR isolates differed in their susceptibility to glps with MIC 90  values ranging from 4.8 μg/ml against  B. subtilis  to 14.4 μg/ml against ESBL  K. pneumoniae, Klebsiella  spp. ESBL and  E. coli  and up to 33 μg/ml against highly resistant strains of  P. aeruginosa . Glps isolated from different honeys showed a similar ability to overcome bacterial resistance to β-lactams suggesting that (a) their mode of action is distinct from other classes of β-lactams and that (b) the common glps structure was the lead structure responsible for the activity. The results of the current study together with our previous evidence of a rapid bactericidal activity of glps demonstrate that glps possess suitable characteristics to be considered a novel antibacterial drug candidate.

frontiers in microbiology

MRJP1-containing glycoproteins isolated from honey, a novel antibacterial drug candidate with broad spectrum activity against multi-drug resistant clinical isolates