Characterisation of permissive and non-permissive phagosome environments during Salmonella systemic infection

Projektinformationen

SalPhagoHet

ID Finanzhilfevereinbarung: 892252

DOI

10.3030/892252

Das Projekt endete am 4 September 2022

EK-Unterschriftsdatum 28 April 2020

Startdatum 1 September 2021

Enddatum 31 August 2023

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten

€ 212 933,76

EU-Beitrag

€ 212 933,76

Koordiniert durch

UNIVERSITY OF NEWCASTLE UPON TYNE
United Kingdom

Periodic Reporting for period 1 - SalPhagoHet (Characterisation of permissive and non-permissive phagosome environments during Salmonella systemic infection)

Berichtszeitraum: 2021-09-01 bis 2023-08-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

The action “Characterisation of permissive and non-permissive phagosome environments during Salmonella systemic infection” looks at the interaction between pathogens and their hosts during bacterial infections. Infectious disease studies often overlook the complexity of immune responses. However, bacterial infections are characterized by complex interactions between pathogen and host. These interactions are disparate and allow some bacterial cells to survive attacks from the immune system. Additionally, it has been shown that some bacteria are protected from antibiotic treatment due to specific host factors surrounding them. The aim of this project is to highlight specific host and pathogen responses in order to identify conditions that allow pathogens to survive and spread and, ultimately, to close these permissive niches.

Antibiotic resistance is a threat to global health. When a bacterium becomes resistant to several antibiotics, it can become very difficult to find a way to treat that specific infection. Additionally, the person infected can easily spread the same multi-drug resistant pathogen to other people. It is becoming increasingly challenging to identify new, efficient drugs and, therefore, novel control strategies to synergise with the immune system are urgently required.

The aim of this action was to identify potential permissive conditions that allow pathogen survival and spread. Specific objectives of this Marie Skłodowska Curie Action (MSCA) have been to (a) develop a new approach of phagosome isolation by fluorescence-activated cell sorting and combine it with sensitive high-resolution mass spectrometry to determine host protein markers over the infection; (b) highlight key bacterial strategies for intracellular survival, potentially identifying novel antimicrobial targets.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

Work was conducted via 2 work packages (WPs). WP1 aimed at determining survival strategies of Salmonella Typhimurium in different immune cells. WP2 sought to establish a novel phagosome isolation approach using fluorescence-activated cell sorting and apply it to understand the antibacterial immune strategies within macrophages and neutrophils. In this action, the Fellow was able to successfully isolate Salmonella-containing phagosomes from infected cells and to use this material for high-resolution mass spectrometry. This allowed simultaneous characterisation of both the Salmonella and the phagosome proteome for the first time.

Results of this MSCA are going to be reported in forthcoming papers on how differences in host-pathogen interactions affect pathogen clearance during bacterial infections. Importantly, the method developed during this MSCA is not limited to Salmonella infection and will be broadly applicable to the study of other important infectious diseases. The data sets collected during the fellowship will be made available to the scientific community and will inform other publications in the coming years.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

Infectious diseases caused by antimicrobial resistant (AMR) pathogens are one of the largest threats to global health today. Antibiotic misuse has induced rapid emergence of resistant bacteria and it is becoming increasingly challenging to identify new, efficient drugs. This MSCA allowed development of new methodologies in the study of bacterial infections. This will have strong repercussions on development of novel strategies in infection control and, ultimately, lead to development of novel antibacterial drugs that will have a major impact on global health.

This MSCA has pushed the frontiers of infection biology as it allowed the Fellow to study the pathogen and the antibacterial immune response simultaneously, with an omics approach. This novel method will shed light on host-pathogen interactions during infections of other intracellular pathogens and immune cell types. Additionally, this method could potentially be applied to the study of indicidual phagosomes highlighting heterogeneous host-pathogen encounters. Such an approach would help developing new target therapies synergising with the host immune system to increase antibacterial activities within phagosomes that would otherwise allow bacteria to proliferate. Through the Fellow’s research on phagosome biology, valuable new understandings are emerging related on how pathogens adapt to hostile immune attacks and what can be done in the future to eradicate antimicrobial resistant pathogens.

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