Direct inhibition of proteases and cervical plasminogen activator by antibiotics

Preterm premature rupture of the fetal membranes and premature delivery are sometimes linked to genital tract infection and activation of proteolytic enzymes that degrade the extracellular matrix. The possible beneficial effect of antibiotics in prevention of preterm premature rupture of fetal membranes and retardation of the onset of labor in some patients with clinical or subclinical infection was explained via their antibacterial efficacy. The aim of this study was to determine the effect of antibiotics on proteolytic enzymes as a possible explanation for the ability of antibiotics to retard preterm labor. The direct effect of four antibiotics on the proteolytic activities of purified collagenase, elastase, plasmin, trypsin, and chymotrypsin and on streptokinase and human cervical plasminogen activator was measured. The macrolide antibiotic erythromycin and the beta-lactam antibiotics penicillin G, cloxacillin, and ampicillin exerted, in most of the tested combinations with the different proteases, inhibitory effects on the proteolytic activities. The present finding that antibiotics directly inhibit proteases may offer an explanation for the beneficial response to antibiotic therapy in some cases of idiopathic preterm labor even in absence of pathogenic bacterial infection.