Umeå University's logo

umu.sePublications
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Studies on the role of class A penicillin-binding proteins in the bacterial cell envelope
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Bacterial cell envelopes are intricate and ever-changing structures that serve numerous defensive and adaptive functions. One of its main structural elements is the peptidoglycan (PG) cell wall, a heteropolymer composed of glycan chains crosslinked by short peptides that forms a net-like structure. The PG layer surrounds the cytoplasmic membrane, providing osmotic stability for the cell and contributing to its shape. PG also holds physiological significance as the enzymes that synthesize and remodel this vital polymer serve as the target of some of our most successful antibiotics, such as penicillin. Penicillin and other β-lactam antibiotics primarily target enzymes known as penicillin-binding proteins (PBPs). This is attributed to the pivotal role of PBPs as the primary enzymes involved in polymerizing and modifying the PG in most bacteria. Due to their importance and therapeutic potential, they have been the focus of research for several decades. In this thesis, we focused on a specific subset of PBPs, the class A PBPs (aPBPs) and their involvement in different cellular processes in two model organisms, Vibrio cholerae and Pseudomonas fluorescens. Using an innovative high-throughput analytical pipeline of the chemical structure of the PG of the entire V. cholerae transposon mutant library we identified a novel bifunctional PBP, PBP1V. This protein, characterized by a putative domain of 186 amino acids near the transpeptidase active site, is mainly conserved among Gamma- and Betaproteobacteria. Phenotypic analysis of PBP1V revealed that while this protein is not essential in V. cholerae, it significantly contributes to its fitness under low osmolarity conditions. The analysis of synthetic lethal interactions involving PBP1V revealed that this protein functionally links the biosynthesis of PG and lipopolysaccharide (LPS). We discovered that unlike the other two aPBPs (PBP1A and PBP1B), PBP1V is needed for LPS homeostasis. In the final chapter of this thesis, we investigated the role of an aPBP in maintaining bacterial rod shape. Using P. fluorescens as a model organism, where the cytoskeletal protein MreB is not essential, we conducted long-term evolution experiments and found that the transpeptidase activity of PBP1A causes lethality when the function of MreB is lost.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2024. , p. 41
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2302
Keywords [en]
Bacterial cell wall, peptidoglycan, cell wall synthesis, aPBPs, lipopolysaccharide, Vibrio cholerae, Pseudomonas fluorescens
National Category
Microbiology
Identifiers
URN: urn:nbn:se:umu:diva-223684ISBN: 978-91-8070-383-3 (print)ISBN: 978-91-8070-384-0 (electronic)OAI: oai:DiVA.org:umu-223684DiVA, id: diva2:1853896
Public defence
2024-05-17, Lärosal A, byggnad 1D, Plan 9, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2024-04-26 Created: 2024-04-23 Last updated: 2024-04-26Bibliographically approved
List of papers
1. Genome-wide peptidoglycan profiling of Vibrio cholerae
Open this publication in new window or tab >>Genome-wide peptidoglycan profiling of Vibrio cholerae
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Microbiology
Research subject
Microbiology
Identifiers
urn:nbn:se:umu:diva-223679 (URN)
Available from: 2024-04-23 Created: 2024-04-23 Last updated: 2024-04-24
2. A novel penicillin-binding protein in Vibrio cholerae important for lipopolysaccharide homeostasis
Open this publication in new window or tab >>A novel penicillin-binding protein in Vibrio cholerae important for lipopolysaccharide homeostasis
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Microbiology
Research subject
Microbiology
Identifiers
urn:nbn:se:umu:diva-223675 (URN)
Available from: 2024-04-23 Created: 2024-04-23 Last updated: 2024-04-24
3. Evolutionary rescue of spherical mreB deletion mutants of the rod-shaped bacterium Pseudomonas fluorescens SBW25
Open this publication in new window or tab >>Evolutionary rescue of spherical mreB deletion mutants of the rod-shaped bacterium Pseudomonas fluorescens SBW25
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Evolutionary Biology Microbiology
Identifiers
urn:nbn:se:umu:diva-223682 (URN)
Available from: 2024-04-23 Created: 2024-04-23 Last updated: 2024-04-24

Open Access in DiVA

spikblad(179 kB)20 downloads
File information
File name SPIKBLAD01.pdfFile size 179 kBChecksum SHA-512
bdc301cf56c19669987a7b45c22f778658b8255a6d7b067ba08b28dd1d704e20c710ad9c3125e4904fc6c046c30beb1dc1b49a3f7cd678f1066d4b9b0e77d5f3
Type spikbladMimetype application/pdf
The full text will be freely available from 2025-05-17 07:00
Available from 2025-05-17 07:00

Authority records

Ritzl-Rinkenberger, Barbara

Search in DiVA

By author/editor
Ritzl-Rinkenberger, Barbara
By organisation
Department of Molecular Biology (Faculty of Medicine)Molecular Infection Medicine Sweden (MIMS)
Microbiology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 464 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf