Person:
Wivagg, Carl N

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Wivagg

First Name

Carl N

Name

Wivagg, Carl N
Author's Publications: search.filters.isAuthorOfPublication.bc4668e6-964a-437f-b355-ca30e77f1011

Search Results

Now showing 1 - 3 of 3
  • Thumbnail Image
    Publication
    Ribosomal mutations promote the evolution of antibiotic resistance in a multidrug environment
    (eLife Sciences Publications, Ltd, 2017) Gomez, James; Kaufmann-Malaga, Benjamin B; Wivagg, Carl N; Kim, Peter B; Silvis, Melanie R; Renedo, Nikolai; Ioerger, Thomas R; Ahmad, Rushdy; Livny, Jonathan; Fishbein, Skye; Sacchettini, James C; Carr, Steven A; Hung, Deborah
    Antibiotic resistance arising via chromosomal mutations is typically specific to a particular antibiotic or class of antibiotics. We have identified mutations in genes encoding ribosomal components in Mycobacterium smegmatis that confer resistance to several structurally and mechanistically unrelated classes of antibiotics and enhance survival following heat shock and membrane stress. These mutations affect ribosome assembly and cause large-scale transcriptomic and proteomic changes, including the downregulation of the catalase KatG, an activating enzyme required for isoniazid sensitivity, and upregulation of WhiB7, a transcription factor involved in innate antibiotic resistance. Importantly, while these ribosomal mutations have a fitness cost in antibiotic-free medium, in a multidrug environment they promote the evolution of high-level, target-based resistance. Further, suppressor mutations can then be easily acquired to restore wild-type growth. Thus, ribosomal mutations can serve as stepping-stones in an evolutionary path leading to the emergence of high-level, multidrug resistance. DOI: http://dx.doi.org/10.7554/eLife.20420.001
  • Thumbnail Image
    Publication
    Bacterial cell wall biogenesis is mediated by SEDS and PBP polymerase families functioning semi-autonomously
    (2016) Cho, Hongbaek; Wivagg, Carl N; Kapoor, Mrinal; Barry, Zachary; Rohs, Patricia; Suh, Hyunsuk; Marto, Jarrod; Garner, Ethan; Bernhardt, Thomas
    Multi-protein complexes organized by cytoskeletal proteins are essential for cell wall biogenesis in most bacteria. Current models of the wall assembly mechanism assume class A penicillin-binding proteins (aPBPs), the targets of penicillin-like drugs, function as the primary cell wall polymerases within these machineries. Here, we use an in vivo cell wall polymerase assay in Escherichia coli combined with measurements of the localization dynamics of synthesis proteins to investigate this hypothesis. We find that aPBP activity is not necessary for glycan polymerization by the cell elongation machinery as is commonly believed. Instead, our results indicate that cell wall synthesis is mediated by two distinct polymerase systems, SEDS-family proteins working within the cytoskeletal machines and aPBP enzymes functioning outside of these complexes. These findings thus necessitate a fundamental change in our conception of the cell wall assembly process in bacteria.
  • Thumbnail Image
    Publication
    MreB filaments align along greatest principal membrane curvature to orient cell wall synthesis
    (eLife Sciences Publications, Ltd, 2018) Hussain, Saman; Wivagg, Carl N; Szwedziak, Piotr; Wong, Felix; Schaefer, Kaitlin; Izoré, Thierry; Renner, Lars D; Holmes, Matthew; Sun, Yingjie; Bisson-Filho, Alexandre W; Walker, Suzanne; Amir, Ariel; Löwe, Jan; Garner, Ethan
    MreB is essential for rod shape in many bacteria. Membrane-associated MreB filaments move around the rod circumference, helping to insert cell wall in the radial direction to reinforce rod shape. To understand how oriented MreB motion arises, we altered the shape of Bacillus subtilis. MreB motion is isotropic in round cells, and orientation is restored when rod shape is externally imposed. Stationary filaments orient within protoplasts, and purified MreB tubulates liposomes in vitro, orienting within tubes. Together, this demonstrates MreB orients along the greatest principal membrane curvature, a conclusion supported with biophysical modeling. We observed that spherical cells regenerate into rods in a local, self-reinforcing manner: rapidly propagating rods emerge from small bulges, exhibiting oriented MreB motion. We propose that the coupling of MreB filament alignment to shape-reinforcing peptidoglycan synthesis creates a locally-acting, self-organizing mechanism allowing the rapid establishment and stable maintenance of emergent rod shape.