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

Brudzynski K, Sjaarda C, Lannigan R - Front Microbiol (2015)

Bottom Line: Their resistance to different classes of antibiotics was confirmed using automated system Vitek 2.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Drug Discovery and Development Department St. Catharines, ON, Canada.

ABSTRACT
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 MIC90 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.

No MeSH data available.


Related in: MedlinePlus

Susceptibility of multidrug resistant clinical isolates to honey glycoproteins. (A) Susceptibility of K. pneumonia (# 1and #19), P. aeruginosa (#34, and #35), E. coli NDM (#4) and E. coli. ESBL (# 7) to G208 and G217. Ampicillin-sensitive E. coli (ATCC14948) served as a control. (B) Susceptibility of MRSA 1 (#5) and ampicillin-sensitive B. subtilis (ATCC 6633) to G208, G207, G217 and G125 isolated from different honeys.
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Figure 3: Susceptibility of multidrug resistant clinical isolates to honey glycoproteins. (A) Susceptibility of K. pneumonia (# 1and #19), P. aeruginosa (#34, and #35), E. coli NDM (#4) and E. coli. ESBL (# 7) to G208 and G217. Ampicillin-sensitive E. coli (ATCC14948) served as a control. (B) Susceptibility of MRSA 1 (#5) and ampicillin-sensitive B. subtilis (ATCC 6633) to G208, G207, G217 and G125 isolated from different honeys.

Mentions: In a similar manner, each of isolates was tested for susceptibility to glycoproteins by well-diffusion assay. The agar plates were divided into three sections; the middle section was used to spread plating of the standard E. coli (ATCC 14948) sensitive to ampicillin while the right and left sections were used to spread plate with the MDR isolates. The susceptibility of isolates to two glycoproteins, G208 and G217, isolated from two different buckwheat honeys, was then evaluated and compared to that of ampicillin-sensitive control. Both glycoproteins have been shown to exhibit antibacterial activity against K. pneumonia 1 and 2 (Table 2; lab number #1 and #19), P. aeruginosa 3 and 4 (lab number #34 and #35), E. coli NDM 4 (lab number #4), and E. coli ESBL 2 (lab number #7). These results indicate that MDR of isolates to antibiotics did not affect antibacterial action of glycoproteins (Figure 3 and Table 2).


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

Brudzynski K, Sjaarda C, Lannigan R - Front Microbiol (2015)

Susceptibility of multidrug resistant clinical isolates to honey glycoproteins. (A) Susceptibility of K. pneumonia (# 1and #19), P. aeruginosa (#34, and #35), E. coli NDM (#4) and E. coli. ESBL (# 7) to G208 and G217. Ampicillin-sensitive E. coli (ATCC14948) served as a control. (B) Susceptibility of MRSA 1 (#5) and ampicillin-sensitive B. subtilis (ATCC 6633) to G208, G207, G217 and G125 isolated from different honeys.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4499756&req=5

Figure 3: Susceptibility of multidrug resistant clinical isolates to honey glycoproteins. (A) Susceptibility of K. pneumonia (# 1and #19), P. aeruginosa (#34, and #35), E. coli NDM (#4) and E. coli. ESBL (# 7) to G208 and G217. Ampicillin-sensitive E. coli (ATCC14948) served as a control. (B) Susceptibility of MRSA 1 (#5) and ampicillin-sensitive B. subtilis (ATCC 6633) to G208, G207, G217 and G125 isolated from different honeys.
Mentions: In a similar manner, each of isolates was tested for susceptibility to glycoproteins by well-diffusion assay. The agar plates were divided into three sections; the middle section was used to spread plating of the standard E. coli (ATCC 14948) sensitive to ampicillin while the right and left sections were used to spread plate with the MDR isolates. The susceptibility of isolates to two glycoproteins, G208 and G217, isolated from two different buckwheat honeys, was then evaluated and compared to that of ampicillin-sensitive control. Both glycoproteins have been shown to exhibit antibacterial activity against K. pneumonia 1 and 2 (Table 2; lab number #1 and #19), P. aeruginosa 3 and 4 (lab number #34 and #35), E. coli NDM 4 (lab number #4), and E. coli ESBL 2 (lab number #7). These results indicate that MDR of isolates to antibiotics did not affect antibacterial action of glycoproteins (Figure 3 and Table 2).

Bottom Line: Their resistance to different classes of antibiotics was confirmed using automated system Vitek 2.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Drug Discovery and Development Department St. Catharines, ON, Canada.

ABSTRACT
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 MIC90 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.

No MeSH data available.


Related in: MedlinePlus