Aims: To develop an antimicrobial peptide with broad spectrum activity against bacteria implicated in biomaterial infection of low toxicity to mammalian cells and retaining its antimicrobial activity when covalently bound to a biomaterial surface. Methods and Results: A synthetic peptide (melimine) was produced by combining portions of the antimicrobial cationic peptides mellitin and protamine. In contrast to the parent peptide melittin which lysed sheep red blood cells at >10 μg ml−1, melimine lysed sheep red blood cells only at concentrations >2500 μg ml−1, well above bactericidal concentrations. Additionally, melimine was found to be stable to heat sterilization. Evaluation by electron microscopy showed that exposure of both Pseudomonas aeruginosa and Staphylococcus aureus to melimine at the minimal inhibitory concentration (MIC) produced changes in the structure of the bacterial membranes. Further, repeated passage of these bacteria in sub‐MIC concentrations of melimine did not result in an increase in the MIC. Melimine was tested for its ability to reduce bacterial adhesion to contact lenses when adsorbed or covalently attached. Approximately 80% reduction in viable bacteria was seen against both P. aeruginosa and S. aureus for 500 μg per lens adsorbed melimine. Covalently linked melimine (18 ± 4 μg per lens) showed >70% reduction of these bacteria to the lens. Conclusions: We have designed and tested a synthetic peptide melimine incorporating active regions of protamine and mellitin which may represent a good candidate for development as an antimicrobial coating for biomaterials. Significance and Impact of the Study: Infection associated with the use of biomaterials remains a major barrier to the long‐term use of medical devices. The antimicrobial peptide melimine is an excellent candidate for development as an antimicrobial coating for such devices.
Lens polymer (possibly associated with surface characteristics) is a prominent factor affecting lipid and protein accumulation. Within a lens polymer type, lens care solutions exhibit varying effectiveness in reducing protein and lipid accumulation.
Staphylococcus is a leading cause of the potentially blinding disease microbial keratitis. Even with the use of antibiotic therapy, the host inflammatory response continues to damage the cornea, which may lead to blindness. Manipulation of the host response may help improve patient outcome from this devastating disease. We aim to understand the contribution of the host response to Staphylococcus aureus infection. A S. aureus keratitis mouse model was developed in both C57BL/6 and BALB/c mice using two different strains of S. aureus (8325‐4 and Staph 38). Twenty‐four hours postinfection, mice were killed and eyes were harvested for enumeration of bacteria, polymorphonuclear leucocytes, chemokines and cytokines. The laboratory strain 8325‐4 was not as virulent as the clinical isolate Staph 38. In vitro data showed a 250‐fold increase in invasion of human corneal epithelial cells by Staph 38 compared to 8325‐4. BALB/c mice were susceptible to S. aureus infection whereas C57BL/6 mice were resistant. The resistant C57BL/6 mice were polarized towards a Th2 response, which may be protective for these mice. IL‐4, IL‐10 and IL‐6 were elevated significantly in C57BL/6 mice infected with Staph 38 (P < 0.05). Macrophage inflammatory peptide (MIP)‐2 was also significantly elevated in C57BL/6 mice (P < 0.001). The susceptible BALB/c mice had a muted cytokine response, which suggests that S. aureus might be ‘walled off’ during infection and might avoid host defences. IL‐4, IL‐10 and IL‐6 cytokines may be protective during Gram‐positive corneal infection and therefore may be useful for adjunct therapies in the treatment of this disease.
The association between possession of toxin gene-related type III secretory system, protease profiles, O serotypes, and antibiotic resistance patterns was characterized genetically and phenotypically in 46 keratitis isolates of Pseudomonas aeruginosa. There was no significant difference in exoU or exoS prevalence among the keratitis strains. Distinct protease profiles were seen in isolates harboring either exoU or exoS genes. One hundred percent (13/13) of serotype E (O:11) strains contained type III secretion system-associated cytotoxin gene exoU. Multidrug resistance was identified in 4% of Australian and 29% of Indian isolates. None of the Australian isolates was resistant to ciprofloxacin. In general, the rate of multidrug resistance in the exoU positive cytotoxic and serotype E (O:11) strains was significantly higher than in exoS positive invasive strains (p < 0.01). The results suggest that multidrug resistance may be more commonly associated with the corneal isolates of P. aeruginosa having type III secretion system-associated cytotoxin gene exoU and belonging to serotype E (O:11) group.
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