Cuomo, Paola (2022) Metabolomics as a means to control human bacterial infections using a Formyl peptide receptor antagonist. [Tesi di dottorato]


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Item Type: Tesi di dottorato
Resource language: English
Title: Metabolomics as a means to control human bacterial infections using a Formyl peptide receptor antagonist
Date: 2022
Number of Pages: 206
Institution: Università degli Studi di Napoli Federico II
Department: Agraria
Dottorato: Biotecnologie
Ciclo di dottorato: 34
Coordinatore del Corso di dottorato:
Capparelli, RosannaUNSPECIFIED
Fulgione, AndreaUNSPECIFIED
Date: 2022
Number of Pages: 206
Keywords: Helicobacter pylori infection, inflammation, gastric and extra-gastric diseases, Formyl peptide receptors, metabolomics, natural molecules.
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/04 - Patologia generale
Date Deposited: 16 Mar 2022 10:58
Last Modified: 28 Feb 2024 14:21

Collection description

Helicobacter pylori (H. pylori) is a major human pathogen causing chronic infection, which generates a state of persistent inflammation, leading to severe gastric and extra-gastric outcomes. In the absence of effective vaccines, treatment of chronic H. pylori infection is the favorite approach for preventing the subsequent clinical implications. However, H. pylori eradication is a difficult clinical practice. Increasing antibiotic resistance, as well as the capacity of H. pylori to successfully evade the host immune system, make it a serious threat for human health. Consequently, novel pharmacological strategies are needed. The present PhD thesis focuses on the identification of new therapeutic agents for the management of H. pylori infection, modulating the host innate immune response, by targeting the Formyl peptide receptors (FPRs). FPRs participate to the host defense by orchestrating the inflammatory response. They have been widely recognized to play critical roles in inflammation-associated diseases. Thus, treatment with FPRs-modulation may be helpful to reduce H. pylori-associated inflammation and prevent the related clinical complications. Among FPRs, our attention was focused on FPR2, as the most attractive and promiscuous target. In this thesis the valorization of invasive marine biomasses for the production of natural anti-inflammatory agents, able to target FPRs, was investigated. Caulerpin, a bis-indole alkaloid isolated from algae of the genus Caulerpa, was identified as potential FPR2 inhibitor. By performing both in silico and in vitro studies, the efficacy of Caulerpin in modulating the immune response against H. pylori, by reverting the FPR2-related signaling cascade, was explored. Moreover, a holistic and omics approach, consisting in metabolomics analysis, was applied as a means useful to examine the role of Caulerpin in attenuating the H. pylori-induced inflammation and the related adverse clinical outcomes. This study might pave the way for a possible future use of Caulerpin as promising therapeutic or adjuvant anti-inflammatory agent against H. pylori infection.


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