Antibody redirection in the clearance of methicillin resistant Staphylococcus aureus sepsis using aptamers conjugated to the immunogenic sugar alpha-1,3-galactose.

摘要

In this study we hypothesized that using whole cell-binding aptamers coupled to alpha-gal (alpha-mers) would enable rescue from MRSA sepsis using a mouse model. The alpha-mer was capped with alpha-gal at the 5' end and a three-carbon cap at the 3' end of the aptamer to increase stability in vivo. The construct was stable in vitro, but was quickly degraded or cleared in vivo using the GTKO mouse model. The alpha-mer therapy alone did not rescue MRSA septic mice, but acted synergistically with vancomycin to alter the tissue distribution of MRSA, and ultimately resulted in significantly lower MRSA concentration in all organs examined, except the spleen, as measured by molecular tracking and histology assessment. Histological assessment showed that mice treated with the alpha-mer and vancomycin had fewer lesions and less inflammation in the heart, especially. These results indicate that use of alpha-mers may be an effective antibiotic adjuvant to reduce MRSA distribution and disease persistence during sepsis, but are not able to act as an independent therapy.