In vitro research has shown that a semipurified protein extract from Sydney Rock Oyster (Saccostrea glomerata) hemolymph demonstrated significant synergistic activity with conventional antibiotics against multiple bacterial pathogens, according to research.
In the study, published in PLOS ONE, researchers found that the hemolymph protein extract (HPE) exhibited marked specificity for Streptococcus species, with minimum bactericidal concentrations (MBCs) as low as 4.42 μg/mL against S pneumoniae strain 19F. When combined with conventional antibiotics, HPE at sub-MBC concentrations (1 to 12 μg/mL) enhanced antibiotic efficacy between two- to 32-fold against various clinically significant pathogens. The extract also demonstrated significant antibiofilm activity, preventing bacterial colonization and effectively killing cells within established biofilms.
"HPE at 3 μg/mL acted synergistically with ampicillin against S pyogenes ATCC 19615, halving the MBC for ampicillin from 0.125 μg/mL (alone) to 0.052 μg/mL (in combination)," the study authors reported. For Staphylococcus aureus ATCC 25923, "HPE at 12 μg/mL caused a marked fivefold reduction in the MBC of ampicillin from 0.50 to 0.094 μg/mL," they added.
The extract maintained optimal activity at –80°C (MBC 7.23 μg/mL), with significantly lower activity at both ambient laboratory temperature (about 24°C) and 37°C (MBC 9.63 μg/mL for both). Activity declined further after exposure to 60°C. Proteomics analysis identified several candidate antimicrobial proteins, with cystatin B-like protein emerging as the likely active component.
Cytotoxicity testing demonstrated safety, with no toxicity observed in A549 human lung cells up to 205 μg/mL—well above therapeutic concentrations. The researchers noted this suggested potential suitability for respiratory applications.
"The strong bactericidal activity of HPE toward the Streptococcus, complementary activity toward other species in HPE-antibiotic combinations, and lack of/minimal activity in both single and combination treatments toward NtHi, may offer insight into the HPE mechanism of action," the study authors wrote.
The synergistic effects were particularly notable against drug-resistant pathogens. For Pseudomonas aeruginosa, HPE reduced the gentamicin MBC from 2.33 μg/mL to 1.0 μg/mL. Against Klebsiella pneumoniae, HPE decreased the trimethoprim MBC eightfold from 16 μg/mL to 2 μg/mL.
The research team, led by Kate Summer, PhD, of Southern Cross University, emphasized that while further development is needed, HPE represents a promising candidate for therapeutic development, particularly given the sustainable aquaculture production of Sydney Rock Oysters.
The study's findings suggested potential applications both as a direct antimicrobial against Streptococcus species and as an antibiotic potentiator against resistant pathogens. The researchers noted that effective concentrations were comparable to antimicrobial peptides currently approved for clinical use or in development pipelines.
The authors declared that they have no competing interests.