Peptides as Therapeutic Molecules to Neutralize Gram-negative Bacterial Lipopolysaccharides in Sepsis and Septic Shock.

During the last years, infections have become a global health emergency, where the appearance of bacteria highly resistant to traditional antibiotics have set off an alarm worldwide. Moreover, the increased incidence and mortality resulting from its aggravated states, sepsis, and septic shock, have been observed with growing concern. In this context, knowing the need for a new concept for treatment, peptides such as antimicrobial peptides (AMP) and host defense peptides (HDP), have started to show interesting properties in the development of new antimicrobial agents and host response modulatory therapies. Nevertheless, since it is a well-known fact that a peptide-based drug development is a long process that consumes a significant number of resources, recent approaches that tend to mitigate these obstacles, have included the implementation of novel in silico strategies for the optimization of naturally occurring AMP and HDP. In this review, we analyze these strategies that seek to improve not only peptide design, but also production, by including the incorporation of computational biology techniques such as molecular dynamics.

New insights into lipopolysaccharide inactivation mechanisms in sepsis.

The complex pathophysiology of sepsis makes it a syndrome with limited therapeutic options and a high mortality rate. Gram-negative bacteria containing lipopolysaccharides (LPS) in their outer membrane correspond to the most common cause of sepsis. Since the gut is considered an important source of LPS, intestinal damage has been considered a cause and a consequence of sepsis. Although important in the maintenance of the intestinal epithelial cell homeostasis, the microbiota has been considered a source of LPS. Recent studies have started to shed light on how sepsis is triggered by dysbiosis, and an increased inflammatory state of the intestinal epithelial cells, expanding the understanding of the gut-liver axis in sepsis. Here, we review the gut-liver interaction in Gram-negative sepsis, exploring the mechanisms of LPS inactivation, including the recently described contribution of an isoform of the cholesteryl-ester transfer protein (CETPI). Although several key questions remain to be answered when the pathophysiology of sepsis is reviewed, new contributions coming to light exploring the way LPS might be inactivated in vivo, suggest that new applications might soon reach the clinical setting.