The study shows that when fetal membranes are infected with E. coli, they quickly make the antimicrobial peptide LL‑37 and other defensins, but these defenses aren’t enough to stop the bacteria or tissue damage. Different parts of the membrane release different peptides over time, and mixing several peptides together works better than any single one in lab tests. This tells us that LL‑37 is part of the body’s early response, but on its own it’s not a magic bullet against infection.

An infectious process into the uterine cavity represents a major endangered condition that compromises the immune privilege of the maternal-fetal unit and increases the risk for preterm birth (PTB) and premature rupture of membranes (PROM). Fetal membranes are active secretors of antimicrobial peptides (AMP), which limit bacterial growth, such as <i>Escherichia coli</i>. Nevertheless, the antibacterial responses displayed by chorioamniotic membranes against a choriodecidual <i>E. coli</i> infection have been briefly studied. The objective of this research was to characterize the profile of synthesis, activity, and spatial distribution of a broad panel of AMPs produced by fetal membranes in response to <i>E. coli</i> choriodecidual infection. Term human chorioamniotic membranes were mounted in a two independent compartment model in which the choriodecidual region was infected with live <i>E. coli</i> (1 &#xd7; 10⁵ CFU/mL). Amnion and choriodecidual AMP tissue levels and TNF-&#x3b1; and IL-1&#x3b2; secretion were measured by the enzyme-linked immunosorbent assay. The passage of bacterium through fetal membranes and their effect on structural continuity was followed for 24 h. Our results showed that <i>E. coli</i> infection caused a progressive mechanical disruption of the chorioamniotic membranes and an activated inflammatory environment. After the challenge, the amnion quickly (2-4 h) induced production of human beta defensins (HBD)-1, HBD-2, and LL-37. Afterwards (8-24 h), the amnion significantly produced HBD-1, HBD-2, HNP-1-3, S100A7, sPLA2, and elafin, whereas the choriodecidua induced LL-37 synthesis. Therefore, we noticed a temporal- and tissue-specific pattern regulation of the synthesis of AMPs by infected fetal membranes. However, fetal membranes were not able to contain the collagen degradation or the bacterial growth and migration despite the battery of produced AMPs, which deeply increases the risk for PTB and PROM. The mixture of recombinant HBDs at low concentrations resulted in increased bactericidal activity compared to each HBD alone in vitro, encouraging further research to study AMP combinations that may offer synergy to control drug-resistant infections in the perinatal period.