Sürdürülebilir Kalkınma Amaçları

  • Derleme MakaleAçık Erişim2025Scopus SJRQ1
    Using synthetic biology to understand the gut-brain axis

    Cesaro, Angela; Broset, Esther; Salimando, Gregory J.; Oztekin, Sebahat; Mai, David; Bennett, Mariko L.; de la Fuente-nunez, Cesar

    Extensive research supports a pivotal role for the gut-brain axis(i.e., the communication pathway between the bacteria in the gut and the brain) in brain health and disease. The interplay between the gut microbiota and the mammalian nervous system appears to shape both adaptive and dysfunctional neurological processes, as it directly affects neurons and neural signaling, the immune response, and metabolism via its effects on hormones, neuropeptides, and neurotransmitters. This review summarizes key findings from the recent literature focused on the interactions between neurons and gut bacteria. By focusing on synthetic biology tools currently employed to study the gut-brain axis, we can enhance our understanding of neuroactive substances released in the gut and potentially identify select molecular candidates that may facilitate the development of personalized therapies.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
    AtıfWoS6OpenAlex6
    Web of Scienceİncele
  • MakaleAçık Erişim2023Scopus SJRQ1
    Structure-function-guided design of synthetic peptides with anti-infective activity derived from wasp venom

    Boaro, Andreia; Ageitos, Lucia; Torres, Marcelo Der Torossian; Blasco, Esther Broset; Oztekin, Sebahat; de la Fuente-nunez, Cesar

    Antimicrobial peptides (AMPs) derived from natural toxins and venoms offer a promising alternative source of antibiotics. Here, through structure-function-guided design, we convert two natural AMPs derived from the venom of the solitary eumenine wasp Eu-menes micado into a-helical AMPs with reduced toxicity that kill Gram-negative bacteria in vitro and in a preclinical mouse model. To identify the sequence determinants conferring antimicrobial ac-tivity, an alanine scan screen and strategic single lysine substitutions are made to the amino acid sequence of these natural peptides. These efforts yield a total of 34 synthetic derivatives, including alanine substituted and lysine-substituted sequences with stabilized a-helical structures and increased net positive charge. The resulting lead synthetic peptides kill the Gram-negative pathogens Escheri-chia coli and Pseudomonas aeruginosa (PAO1 and PA14) by rapidly permeabilizing both their outer and cytoplasmic membranes, exhibit anti-infective efficacy in a mouse model by reducing bacte-rial loads by up to three orders of magnitude, and do not readily select for bacterial resistance.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
    AtıfWoS34OpenAlex39
    Web of SciencePubMedİncele