Beschreibung:
<jats:title>Abstract</jats:title>
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<jats:title>Objectives</jats:title>
<jats:p>The objective of this study was to investigate the therapeutic potential of the insect metalloproteinase inhibitor (IMPI) from Galleria mellonella, the only known specific inhibitor of M4 metalloproteinases.</jats:p>
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<jats:title>Methods</jats:title>
<jats:p>The fusion protein IMPI-GST (glutathione-S-transferase) was produced by fermentation in Escherichia coli and was tested for its ability to inhibit the proteolytic activity of the M4 metalloproteinases thermolysin and Pseudomonas elastase (PE), the latter a key virulence factor of the wound-associated and antibiotic-resistant pathogen Pseudomonas aeruginosa. We also tested the ability of IMPI to inhibit the secretome (Sec) of a P. aeruginosa strain obtained from a wound.</jats:p>
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<jats:title>Key findings</jats:title>
<jats:p>We found that IMPI-GST inhibited thermolysin and PE in vitro and increased the viability of human keratinocytes exposed to Sec by inhibiting detachment caused by changes in cytoskeletal morphology. IMPI-GST also improved the cell migration rate in an in vitro wound assay and reduced the severity of necrosis caused by Sec in an ex vivo porcine wound model.</jats:p>
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<jats:title>Conclusions</jats:title>
<jats:p>The inhibition of virulence factors is a novel therapeutic approach against antibiotic resistant bacteria. Our results indicate that IMPI is a promising drug candidate for the treatment of P. aeruginosa infections.</jats:p>
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