Leiv Sigve Håvarstein

Norwegian University of Life Sciences

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Daniel Straume

Norwegian University of Life Sciences

Ingolf F. Nes

Norwegian University of Life Sciences

Gro Anita Stamsås

Norwegian University of Life Sciences

Morten Kjos

Norwegian University of Life Sciences

J.A. Hermoso

Consejo Superior de Investigaciones Científicas

Ola Johnsborg

Norwegian University of Life Sciences

Helge Holo

Norwegian University of Life Sciences

Kari Helene Berg

Norwegian University of Life Sciences

Martín Alcorlo

National University of Singapore

Zhian Salehian

Norwegian University of Life Sciences

Cooperative Institutions

Norwegian University of Life Sciences

Centre National de la Recherche Scientifique

University of Oslo

University of Bergen

The Research Council of Norway

Norwegian Veterinary Institute

Institut de Biologie Structurale

Commissariat à l'Énergie Atomique et aux Énergies Alternatives

Université Grenoble Alpes

Consejo Superior de Investigaciones Científicas

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UTTALELSE OM BASF Plant Science GmbH GENMODIFISERT POTET AMYLOPEKTIN POTET EVENT EH92-527-1 (EFSA/GMO/UK/2005/14)

10 (2005)

Ingolf F. Nes Knut G Berdal Grethe Synnøve Foss Leiv Sigve Håvarstein Sonja S. Klemsdal

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A qualitative assessment of the risks of transmission of microorganisms to humans resulting from the consumption of raw milk and raw cream in Norway. Panel for Biological Hazards, Norwegian Scientific Committee for Food Safety

40 (2006)

Yngvild Wasteson Hans Blom Kåre Fossum E. Arne Høiby Judith Narvhus

Norwegian

Biological hazard

Consumption

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Citations (1)

Two species of the phosphoprotein mRNA with differently edited reading frames discovered in measles virus infected Vero cells

Apmis (1989)

Karl-H. Kalland Leiv Sigve Håvarstein Curt Endresen Gunnar Haukenes

One cDNA clone representing the phosphoprotein mRNA sequence of the Edmonston strain of measles virus contained 4 G nucleotides at a particular position. Two other clones contained 3 G nucleotides at the same position. Otherwise the nucleotide sequence were identical. The mRNA with 3 G nucleotides codes for the 70 kD phosphoprotein. The mRNA with 4 G nucleotides may code for a putative new peptide with 231 aminoterminal amino acids in common with the P protein whereas the 68 carboxyterminal amino acids are different from any amino acid sequence of the phosphoprotein. Thus the consequence of the insertion of one additional G is a translational shift to a shorter open reading frame. There are several indications that the observation is of biological significance.

Phosphoprotein

Reading frame

Morbillivirus

10.1111/j.1699-0463.1989.tb00489.x

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Citations (2)

Structural basis of PcsB-mediated cell separation in Streptococcus pneumoniae

Nature Communications (2014)

Sergio G. Bartual Daniel Straume Gro Anita Stamsås Inés G. Muñoz Carlos Alfonso

Coiled coil

Lipid II

10.1038/ncomms4842

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Structure of the Large Extracellular Loop of FtsX and Its Interaction with the Essential Peptidoglycan Hydrolase PcsB in Streptococcus pneumoniae

mBio (2019)

Britta E. Rued Martín Alcorlo Katherine A. Edmonds Siseth Martínez‐Caballero Daniel Straume

FtsX is a ubiquitous bacterial integral membrane protein involved in cell division that regulates the activity of peptidoglycan (PG) hydrolases. FtsX is representative of a large group of ABC3 superfamily proteins that function as “mechanotransmitters,” proteins that relay signals from the inside to the outside of the cell. Here, we present a structural characterization of the large extracellular loop, ECL1, of FtsX from the opportunistic human pathogen S. pneumoniae . We show the molecular nature of the direct interaction between the peptidoglycan hydrolase PcsB and FtsX and demonstrate that this interaction is essential for cell viability. As such, FtsX represents an attractive, conserved target for the development of new classes of antibiotics.

Hydrolase

Lysin

10.1128/mbio.02622-18

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Citations (39)

Prevention of EloR/KhpA heterodimerization by introduction of site-specific amino acid substitutions renders the essential elongasome protein PBP2b redundant in Streptococcus pneumoniae

Scientific Reports (2019)

Anja Ruud Winther Morten Kjos Gro Anita Stamsås Leiv Sigve Håvarstein Daniel Straume

Abstract The RNA binding proteins EloR and KhpA are important components of the regulatory network that controls and coordinates cell elongation and division in S . pneumoniae . Loss of either protein reduces cell length, and makes the essential elongasome proteins PBP2b and RodA dispensable. It has been shown previously in formaldehyde crosslinking experiments that EloR co-precipitates with KhpA, indicating that they form a complex in vivo . In the present study, we used 3D modeling and site directed mutagenesis in combination with protein crosslinking to further study the relationship between EloR and KhpA. Protein-protein interaction studies demonstrated that KhpA forms homodimers and that KhpA in addition binds to the KH-II domain of EloR. Site directed mutagenesis identified isoleucine 61 (I61) as crucial for KhpA homodimerization. When substituting I61 with phenylalanine, KhpA lost the ability to homodimerize, while it still interacted clearly with EloR. In contrast, both homo- and heterodimerization were lost when I61 was substituted with tyrosine. By expressing these KhpA versions in S . pneumoniae , we were able to show that disruption of EloR/KhpA heterodimerization makes the elongasome redundant in S . pneumoniae . Of note, loss of KhpA homodimerization did not give rise to this phenotype, demonstrating that the EloR/KhpA complex is crucial for regulating the activity of the elongasome. In support of this conclusion, we found that localization of KhpA to the pneumococcal mid-cell region depends on its interaction with EloR. Furthermore, we found that the EloR/KhpA complex co-localizes with FtsZ throughout the cell cycle.

Penicillin binding proteins

10.1038/s41598-018-38386-6

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Citations (16)

New insights into the pneumococcal fratricide: relationship to clumping and identification of a novel immunity factor

Molecular Microbiology (2005)

Leiv Sigve Håvarstein Bernard Martin Ola Johnsborg Chantal Granadel Jean‐Pierre Claverys

Summary In 1971, Tomasz and Zanati discovered that competent pneumococci have a tendency to form aggregates when pelleted by centrifugation and resuspended in 0.01 N HCl by brief vortexing. Interestingly, no clumping was observed with parallel cultures of non‐competent cells treated in the same way. We set out to elucidate the mechanism behind this striking phenomenon, and were able to show that it depends on extracellular DNA that is presumably released by so‐called competence‐induced cell lysis. Competence‐induced cell lysis, which was first described a few years ago, seems to rely on the concerted action of several murein hydrolases. Our results confirmed and extended previous findings by showing that competence‐induced aggregation is abolished in a lytA–lytC double mutant, and absolutely requires CbpD and its N‐terminal CHAP amidase domain. Furthermore, we discovered a novel competence stimulating peptide (CSP)‐induced immunity protein, encoded by the early competence gene comM ( spr1762 ), which protects competent pneumococci against their own lysins. Together, the murein hydrolases and the immunity protein constitutes a CSP‐controlled mechanism that allows competent pneumococci to commit fratricide by killing non‐competent pneumococci sharing the same ecological niche. Through such predatory behaviour, pneumococci can get access to transforming DNA and nutrients, promote the release of virulence factors, and at the same time get rid of competitors.

Lysin

Amidase

10.1111/j.1365-2958.2005.05021.x

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Citations (144)

Competence-induced fratricide in streptococci. Mol. Microbiol

HAL (Le Centre pour la Communication Scientifique Directe) (2007)

J.P. Claverys Bernard Martin Leiv Sigve Håvarstein

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Citations (5)

Comments on: The opinion of the Agence française de sécurité sanitaire (Afssa) on changes to the control measures for sheep and goat herds in which a case of classical or atypical scrapie has been detected. Opinion of the Panel on Biological Hazards & Panel on Animal Health and Animal Welfare of the Norwegian Scientific Committee for Food Safety

9 (2007)

Espen Rimstad Leiv Sigve Håvarstein Georg Kapperud Jørgen Lassen Bjørn Tore Lunestad

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Class A PBPs have a distinct and unique role in the construction of the pneumococcal cell wall

Proceedings of the National Academy of Sciences (2020)

Daniel Straume Katarzyna Wiaroslawa Piechowiak Silje Olsen Gro Anita Stamsås Kari Helene Berg

In oval-shaped Streptococcus pneumoniae, septal and longitudinal peptidoglycan syntheses are performed by independent functional complexes: the divisome and the elongasome. Penicillin-binding proteins (PBPs) were long considered the key peptidoglycan-synthesizing enzymes in these complexes. Among these were the bifunctional class A PBPs, which are both glycosyltransferases and transpeptidases, and monofunctional class B PBPs with only transpeptidase activity. Recently, however, it was established that the monofunctional class B PBPs work together with transmembrane glycosyltransferases (FtsW and RodA) from the shape, elongation, division, and sporulation (SEDS) family to make up the core peptidoglycan-synthesizing machineries within the pneumococcal divisome (FtsW/PBP2x) and elongasome (RodA/PBP2b). The function of class A PBPs is therefore now an open question. Here we utilize the peptidoglycan hydrolase CbpD that targets the septum of S. pneumoniae cells to show that class A PBPs have an autonomous role during pneumococcal cell wall synthesis. Using assays to specifically inhibit the function of PBP2x and FtsW, we demonstrate that CbpD attacks nascent peptidoglycan synthesized by the divisome. Notably, class A PBPs could process this nascent peptidoglycan from a CbpD-sensitive to a CbpD-resistant form. The class A PBP-mediated processing was independent of divisome and elongasome activities. Class A PBPs thus constitute an autonomous functional entity which processes recently formed peptidoglycan synthesized by FtsW/PBP2×. Our results support a model in which mature pneumococcal peptidoglycan is synthesized by three functional entities, the divisome, the elongasome, and bifunctional PBPs. The latter modify existing peptidoglycan but are probably not involved in primary peptidoglycan synthesis.

Penicillin binding proteins

Lipid II

10.1073/pnas.1917820117

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Citations (48)