AUTHOR=Brudzynski Katrina , Sjaarda Calvin , Lannigan Robert 

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

JOURNAL=Frontiers in Microbiology

VOLUME=6

YEAR=2015

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2015.00711

DOI=10.3389/fmicb.2015.00711

ISSN=1664-302X

ABSTRACT=<p>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 <italic>Bacillus subtilis</italic> and Gram-negative <italic>Escherichia coli</italic> 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 <italic>Staphylococcus aureus</italic> (MRSA), four <italic>Pseudomonas aeruginosa</italic>, two <italic>Klebsiella pneumoniae</italic>, two vancomycin-resistant <italic>Enterococci</italic> (VRE), and five ESBL identified as one <italic>Proteus mirabilis</italic>, three <italic>E. coli</italic>, and one <italic>E. coli</italic> 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<sub>90</sub> values ranging from 4.8 μg/ml against <italic>B. subtilis</italic> to 14.4 μg/ml against ESBL <italic>K. pneumoniae, Klebsiella</italic> spp. ESBL and <italic>E. coli</italic> and up to 33 μg/ml against highly resistant strains of <italic>P. aeruginosa</italic>. 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.</p>