Project

Back to overview

Structure and mechanism of the cell wall biogenesis machinery from Gram-positive pathogenic bacteria

English title Structure and mechanism of the cell wall biogenesis machinery from Gram-positive pathogenic bacteria
Applicant Perez Camilo
Number 170607
Funding scheme SNSF Professorships
Research institution Biozentrum Universität Basel
Institution of higher education University of Basel - BS
Main discipline Molecular Biology
Start/End 01.07.2017 - 30.06.2021
Approved amount 1'599'981.00
Show all

All Disciplines (2)

Discipline
Molecular Biology
Biophysics

Keywords (8)

Molecular mechanism; Protein function; Membrane proteins; Cell wall; Structure determination; Gram-positive pathogens; Mycobacterium tuberculosis; Antimicrobials

Lay Summary (German)

Lead
Wir erforschen auf molekularer Ebene die Vorgänge, die bei der Zellwand-Biogenese von bakteriellen Krankheitserregern eine grundlegende Rolle spielen.Bakterielle Infektionen stellen ein grosses Problem für die öffentliche Gesundheit dar. Dieses wird durch das Auftreten Antibiotika-resistenter Bakterien noch verschärft. Um neuartige therapeutische Strategien zur Bekämpfung von Infektionen entwickeln zu können, ist es daher wichtig, die grundlegenden Prozesse, die für das Überleben von Bakterien bedeutsam sind, im Detail zu verstehen.
Lay summary

Die Zellwand als antibakterieller Angriffspunkt
Die Zellwand von Bakterien erfüllt eine wichtige Schutzfunktion gegen Antibiotika und die Immunabwehr des Wirtes. Da die Zellwand-Synthese auch für die Virulenz und das Überleben von Bakterien von Bedeutung ist, gilt sie als bevorzugter Angriffspunkt bei der Entwicklung antibakterieller Wirkstoffe. Doch trotz ihrer Bedeutung, sind wichtige Fragen bezüglich der Struktur, dem Mechanismus sowie der Biochemie für zahlreiche an der Zellwand-Biosynthese beteiligten Proteine immer noch ungeklärt.

 

Mechanismen der Zellwand-Biogenese
In unserer Forschung kombinieren wir in vitro und in vivo Aktivitätstests mit hochaufgelösten Strukturen von Membranproteinen, die bei der Biosynthese der Zellwand eine wichtige Rolle spielen. Wir möchten die zugrundeliegenden molekularen Mechanismen besser verstehen und mögliche Methoden finden, die Aktivität der Synthesewege zu modulieren oder zu hemmen.

Direct link to Lay Summary Last update: 15.03.2017

Responsible applicant and co-applicants

Employees

Collaboration

Group / person Country
Types of collaboration
Prof. Jean-Louis Reymond/University of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Sebastien Gagneux/Swiss Tropical and Public Health Institute Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Jan-Willem Veening/University of Lausanne Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Sebastian Hiller/Biozentrum/University of Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Gordon Research Conference Mechanisms of Membrane Transport Individual talk Structure and mechanism of a lipoteichoic-acid-anchor flippase 22.06.2019 Boston, United States of America Perez Camilo; Zhang Bing;
Murnau Conference, Structural Biology Poster Strcutural Studies on Cell Wall Membrane Proteins 26.09.2018 Murnau, Germany Bärland Natalie; Perez Camilo; Zhang Bing;
PhD retreat Biozentrum, Structural Biology Focal Area. Poster Translocation processes involved in cell wall biosynthesis 07.06.2018 Engelberg, Switzerland Bärland Natalie; Zhang Bing;
Biozentrum Symposium 2018 Talk given at a conference Translocation processes involved in cell wall biosynthesis 17.01.2018 Basel, Switzerland Zhang Bing; Bärland Natalie; Perez Camilo;
Molecular Basis of Life - GBM conference Talk given at a conference Conformational landscape of an active lipid-linked oligosaccharide flippase 25.09.2017 Bochum, Germany Perez Camilo;


Self-organised

Title Date Place
Gordon Research Seminar/Conference in ligand recognition and molecular gating 03.03.2018 Ventura, CA., United States of America

Associated projects

Number Title Start Funding scheme
177084 Efficient cryo electron microscopy of macromolecular assemblies and membrane proteins 01.09.2018 R'EQUIP

Abstract

Bacterial infections represent a major public health problem of broad concern to countries and multiple sectors, augmented by increasing occurrence of strains resistant to antibacterial agents. Antimicrobial resistance is a growing threat for the effective treatment of infections and the achievements of modern medicine, e.g. organ transplants, cancer therapy, treatment of chronic diseases. The impact on the costs and difficulty of patient treatments is high, and worst on treatments of vulnerable patients, leading to prolonged illness and increased mortality. Some of the most dangerous human pathogens are Gram-positive bacteria such as, Clostridium difficile, Staphylococcus aureus, Streptococcus pneumoniae and the acid-fast bacteria Mycobacterium tuberculosis. In order to develop new chemotherapeutic strategies to overcome infections, it is necessary to understand fundamental processes relevant for bacterial survival in detail. The cell wall of Gram-positive and acid-fast bacteria exerts important protective functions against host defenses and antibiotics; its biogenesis is a preferred target for the development of antibacterial agents, because it includes several essential pathways for virulence and survival. Despite its great importance, structural, mechanistic and fundamental biochemical aspects of many proteins, in particular membrane proteins, participating in Gram-positive and acid-fast cell wall biosynthesis are scarce. This is due in part to the challenge that accompanies the work with membrane proteins and the difficulty in access to their natural substrates. Our research focuses on the structural and biochemical investigation of relevant membrane proteins, involved in cell wall biosynthesis. In combination, our results will provide an understanding of the molecular processes mediated by these proteins, and describe potential modes of activity modulation and inhibition.
-