Prof. Dr. Marc Erhardt

Profil

• Aufbau und Funktion des Typ-III Proteinexportsystems des bakteriellen Flagellums

  Quelle ↗

  Förderer: DFG Sachbeihilfe Zeitraum: 11/2017 - 06/2020 Projektleitung: Prof. Dr. Marc Erhardt

• Entscheidungsfindung von Zellen in multizellulären Systemen: Das 'Least microEnvironmental Uncertainty' Prinzip (LEUP)

  Quelle ↗

  Förderer: Volkswagen Stiftung Zeitraum: 01/2020 - 12/2025 Projektleitung: Prof. Dr. Marc Erhardt

• Qualitätsmanagement während der Assemblierung von bakteriellen Typ-III Sekretionssystemen – eine vergleichende Studie des Aufbaus von Flagellen und Injektisomen

  Quelle ↗

  Förderer: DFG Sachbeihilfe Zeitraum: 10/2019 - 03/2023 Projektleitung: Prof. Dr. Marc Erhardt

• Reconstructing the Coordinated Self-Assembly of a Bacterial Nanomachine (BacNanoMachine)

  Quelle ↗

  Förderer: Horizon 2020: ERC Consolidator Grant Zeitraum: 10/2020 - 09/2026 Projektleitung: Prof. Dr. Marc Erhardt

• Untersuchung des immunogenen Potenzials von Flagella für Impfstoffträger auf Salmonellenbasis

  Quelle ↗

  Zeitraum: 01/2017 - 06/2018 Projektleitung: Prof. Dr. Marc Erhardt

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• Energy source of flagellar type III secretion

  2008

  Nature · 309 Zitationen · DOI

• Structure and Function of Stator Units of the Bacterial Flagellar Motor

  2020

  Cell · 254 Zitationen · DOI

• Bacterial Nanomachines: The Flagellum and Type III Injectisome

  2010

  Cold Spring Harbor Perspectives in Biology · 247 Zitationen · DOI

  The bacterial flagellum and the virulence-associated injectisome are complex, structurally related nanomachines that bacteria use for locomotion or the translocation of virulence factors into eukaryotic host cells. The assembly of both structures and the transfer of extracellular proteins is mediated by a unique, multicomponent transport apparatus, the type III secretion system. Here, we discuss the significant progress that has been made in recent years in the visualization and functional characterization of many components of the type III secretion system, the structure of the bacterial flagellum, and the injectisome complex.

• A dual function for chaperones SSB–RAC and the NAC nascent polypeptide–associated complex on ribosomes

  2010

  The Journal of Cell Biology · 218 Zitationen · DOI

  The yeast Hsp70/40 system SSB-RAC (stress 70 B-ribosome-associated complex) binds to ribosomes and contacts nascent polypeptides to assist cotranslational folding. In this study, we demonstrate that nascent polypeptide-associated complex (NAC), another ribosome-tethered system, is functionally connected to SSB-RAC and the cytosolic Hsp70 network. Simultaneous deletions of genes encoding NAC and SSB caused conditional loss of cell viability under protein-folding stress conditions. Furthermore, NAC mutations revealed genetic interaction with a deletion of Sse1, a nucleotide exchange factor regulating the cytosolic Hsp70 network. Cells lacking SSB or Sse1 showed protein aggregation, which is enhanced by additional loss of NAC; however, these mutants differ in their potential client repertoire. Aggregation of ribosomal proteins and biogenesis factors accompanied by a pronounced deficiency in ribosomal particles and translating ribosomes only occurs in ssbDelta and nacDeltassbDelta cells, suggesting that SSB and NAC control ribosome biogenesis. Thus, SSB-RAC and NAC assist protein folding and likewise have important functions for regulation of ribosome levels. These findings emphasize the concept that ribosome production is coordinated with the protein-folding capacity of ribosome-associated chaperones.

• Methylation of Salmonella Typhimurium flagella promotes bacterial adhesion and host cell invasion

  2020

  Nature Communications · 133 Zitationen · DOI

  The long external filament of bacterial flagella is composed of several thousand copies of a single protein, flagellin. Here, we explore the role played by lysine methylation of flagellin in Salmonella, which requires the methylase FliB. We show that both flagellins of Salmonella enterica serovar Typhimurium, FliC and FljB, are methylated at surface-exposed lysine residues by FliB. A Salmonella Typhimurium mutant deficient in flagellin methylation is outcompeted for gut colonization in a gastroenteritis mouse model, and methylation of flagellin promotes bacterial invasion of epithelial cells in vitro. Lysine methylation increases the surface hydrophobicity of flagellin, and enhances flagella-dependent adhesion of Salmonella to phosphatidylcholine vesicles and epithelial cells. Therefore, posttranslational methylation of flagellin facilitates adhesion of Salmonella Typhimurium to hydrophobic host cell surfaces, and contributes to efficient gut colonization and host infection.

• An infrequent molecular ruler controls flagellar hook length in Salmonella enterica

  2011

  The EMBO Journal · 132 Zitationen · DOI

• Efficiency of Conditionally Attenuated Salmonella enterica Serovar Typhimurium in Bacterium-Mediated Tumor Therapy

  2015

  mBio · 96 Zitationen · DOI

  Cancer has become the second most frequent cause of death in industrialized countries. This and the drawbacks of routine therapies generate an urgent need for novel treatment options. Applying appropriately modified S. Typhimurium for therapy represents the major challenge of bacterium-mediated tumor therapy. In the present study, we demonstrated that Salmonella bacteria conditionally modified in their LPS phenotype exhibit a safe tumor-targeting phenotype. Moreover, they could represent a suitable vehicle to shuttle therapeutic compounds directly into cancerous tissue without harming the host.

• Enhancement of IFNγ Production by Distinct Commensals Ameliorates Salmonella-Induced Disease

  2017

  Cell Host & Microbe · 95 Zitationen · DOI

• YdiV: a dual function protein that targets FlhDC for ClpXP‐dependent degradation by promoting release of DNA‐bound FlhDC complex

  2012

  Molecular Microbiology · 95 Zitationen · DOI

  YdiV is an EAL-like protein that acts as a post-transcriptional, negative regulator of the flagellar master transcriptional activator complex, FlhD(4)C(2), in Salmonella enterica to couple flagellar gene expression to nutrient availability. Mutants defective in ClpXP protease no longer exhibit YdiV-dependent inhibition of FlhD(4)C(2)-dependent transcription under moderate YdiV expression conditions. ClpXP protease degrades FlhD(4)C(2), and this degradation is accelerated in the presence of YdiV. YdiV complexed with both free and DNA-bound FlhD(4)C(2); and stripped FlhD(4)C(2) from DNA. A L22H substitution in FlhD was isolated as insensitive to YdiV inhibition. The FlhD L22H substitution prevented the interaction of YdiV with free FlhD(4)C(2) and the ability of YdiV to release FlhD(4)C(2) bound to DNA. These results demonstrate that YdiV prevents FlhD(4)C(2)-dependent flagellar gene transcription and acts as a putative adaptor to target FlhD(4)C(2) for ClpXP-dependent proteolysis. Our results suggest that YdiV is an EAL-like protein that has evolved from a dicyclic-GMP phosphodiesterase into a dual-function regulatory protein that connects flagellar gene expression to nutrient starvation.

• The Salmonella Spi1 Virulence Regulatory Protein HilD Directly Activates Transcription of the Flagellar Master Operon<i>flhDC</i>

  2014

  Journal of Bacteriology · 92 Zitationen · DOI

  Infection of intestinal epithelial cells is dependent on the Salmonella enterica serovar Typhimurium pathogenicity island 1 (Spi1)-encoded type III injectisome system and flagellar motility. Thus, the expression of virulence and flagellar genes is subject to tight regulatory control mechanisms in order to ensure the correct spatiotemporal production of the respective gene products. In this work, we reveal a new level of cross-regulation between the Spi1 and flagellar regulatory systems. Transposon mutagenesis identified a class of mutants that prevented flhDC autorepression by overexpressing HilD. HilD, HilC, RtsA, and HilA comprise a positive regulatory circuit for the expression of the Spi1 genes. Here, we report a novel transcriptional cross talk between the Spi1 and flagellar regulons where HilD transcriptionally activates flhDC gene expression by binding to nucleotides -68 to -24 upstream from the P5 transcriptional start site. We additionally show that, in contrast to the results of a previous report, HilA does not affect flagellar gene expression. Finally, we discuss a model of the cross-regulation network between Spi1 and the flagellar system and propose a regulatory mechanism via the Spi1 master regulator HilD that would prime flagellar genes for rapid reactivation during host infection.

• Bacterial flagella grow through an injection-diffusion mechanism

  2017

  eLife · 91 Zitationen · DOI

  The bacterial flagellum is a self-assembling nanomachine. The external flagellar filament, several times longer than a bacterial cell body, is made of a few tens of thousands subunits of a single protein: flagellin. A fundamental problem concerns the molecular mechanism of how the flagellum grows outside the cell, where no discernible energy source is available. Here, we monitored the dynamic assembly of individual flagella using in situ labelling and real-time immunostaining of elongating flagellar filaments. We report that the rate of flagellum growth, initially ∼1,700 amino acids per second, decreases with length and that the previously proposed chain mechanism does not contribute to the filament elongation dynamics. Inhibition of the proton motive force-dependent export apparatus revealed a major contribution of substrate injection in driving filament elongation. The combination of experimental and mathematical evidence demonstrates that a simple, injection-diffusion mechanism controls bacterial flagella growth outside the cell.

• ATPase-Independent Type-III Protein Secretion in Salmonella enterica

  2014

  PLoS Genetics · 90 Zitationen · DOI

  Type-III protein secretion systems are utilized by gram-negative pathogens to secrete building blocks of the bacterial flagellum, virulence effectors from the cytoplasm into host cells, and structural subunits of the needle complex. The flagellar type-III secretion apparatus utilizes both the energy of the proton motive force and ATP hydrolysis to energize substrate unfolding and translocation. We report formation of functional flagella in the absence of type-III ATPase activity by mutations that increased the proton motive force and flagellar substrate levels. We additionally show that increased proton motive force bypassed the requirement of the Salmonella pathogenicity island 1 virulence-associated type-III ATPase for secretion. Our data support a role for type-III ATPases in enhancing secretion efficiency under limited secretion substrate concentrations and reveal the dispensability of ATPase activity in the type-III protein export process.

• Strategies to Block Bacterial Pathogenesis by Interference with Motility and Chemotaxis

  2016

  Current topics in microbiology and immunology · 89 Zitationen · DOI

• Regulation of Flagellum Biosynthesis in Response to Cell Envelope Stress in <i>Salmonella enterica</i> Serovar Typhimurium

  2018

  mBio · 87 Zitationen · DOI

  Flagellum-driven motility of <i>Salmonella enterica</i> serovar Typhimurium facilitates host colonization. However, the large extracellular flagellum is also a prime target for the immune system. As consequence, expression of flagella is bistable within a population of <i>Salmonella</i>, resulting in flagellated and nonflagellated subpopulations. This allows the bacteria to maximize fitness in hostile environments. The degenerate EAL domain protein RflP (formerly YdiV) is responsible for the bistable expression of flagella by directing the flagellar master regulatory complex FlhD₄C₂ with respect to proteolytic degradation. Information concerning the environmental cues controlling expression of <i>rflP</i> and thus about the bistable flagellar biosynthesis remains ambiguous. Here, we demonstrated that RflP responds to cell envelope stress and alterations of outer membrane integrity. Lipopolysaccharide (LPS) truncation mutants of <i>Salmonella</i> Typhimurium exhibited increasing motility defects due to downregulation of flagellar gene expression. Transposon mutagenesis and genetic profiling revealed that σ²⁴ (RpoE) and Rcs phosphorelay-dependent cell envelope stress response systems sense modifications of the lipopolysaccaride, low pH, and activity of the complement system. This subsequently results in activation of RflP expression and degradation of FlhD₄C₂ via ClpXP. We speculate that the presence of diverse hostile environments inside the host might result in cell envelope damage and would thus trigger the repression of resource-costly and immunogenic flagellum biosynthesis via activation of the cell envelope stress response.<b>IMPORTANCE</b> Pathogenic bacteria such as <i>Salmonella</i> Typhimurium sense and adapt to a multitude of changing and stressful environments during host infection. At the initial stage of gastrointestinal colonization, <i>Salmonella</i> uses flagellum-mediated motility to reach preferred sites of infection. However, the flagellum also constitutes a prime target for the host's immune response. Accordingly, the pathogen needs to determine the spatiotemporal stage of infection and control flagellar biosynthesis in a robust manner. We found that <i>Salmonella</i> uses signals from cell envelope stress-sensing systems to turn off production of flagella. We speculate that downregulation of flagellum synthesis after cell envelope damage in hostile environments aids survival of <i>Salmonella</i> during late stages of infection and provides a means to escape recognition by the immune system.

• <i>aroA</i> -Deficient Salmonella enterica Serovar Typhimurium Is More Than a Metabolically Attenuated Mutant

  2016

  mBio · 78 Zitationen · DOI

  Recombinant attenuated bacterial vector systems based on genetically engineered Salmonella have been developed as highly potent vaccines. Due to the pathogenic properties of Salmonella, efficient attenuation is required for clinical applications. Since the hallmark study by Hoiseth and Stocker in 1981 (S. K. Hoiseth and B. A. D. Stocker, Nature 291:238-239, 1981, http://dx.doi.org/10.1038/291238a0), the auxotrophic ΔaroA mutation has been generally considered safe and universally used to attenuate bacterial strains. Here, we are presenting the remarkable finding that a deletion of aroA leads to pronounced alterations of gene expression, metabolism, and cellular physiology, which resulted in increased immunogenicity, virulence, and adjuvant potential of Salmonella. These results suggest that the enhanced immunogenicity of aroA-deficient Salmonella strains might be advantageous for optimizing bacterial vaccine carriers and immunotherapy. Accordingly, we demonstrate a superior performance of ΔaroA Salmonella in bacterium-mediated tumor therapy. In addition, the present study highlights the importance of a functional shikimate pathway to sustain bacterial physiology and metabolism.

• Structural basis of torque generation in the bi-directional bacterial flagellar motor

  2021

  Trends in Biochemical Sciences · 73 Zitationen · DOI

  The flagellar stator unit is an oligomeric complex of two membrane proteins (MotA₅B₂) that powers bi-directional rotation of the bacterial flagellum. Harnessing the ion motive force across the cytoplasmic membrane, the stator unit operates as a miniature rotary motor itself to provide torque for rotation of the flagellum. Recent cryo-electron microscopic (cryo-EM) structures of the stator unit provided novel insights into its assembly, function, and subunit stoichiometry, revealing the ion flux pathway and the torque generation mechanism. Furthermore, in situ cryo-electron tomography (cryo-ET) studies revealed unprecedented details of the interactions between stator unit and rotor. In this review, we summarize recent advances in our understanding of the structure and function of the flagellar stator unit, torque generation, and directional switching of the motor.

• Mechanism of type‐<scp>III</scp> protein secretion: Regulation of <scp>F</scp>lh<scp>A</scp> conformation by a functionally critical charged‐residue cluster

  2017

  Molecular Microbiology · 72 Zitationen · DOI

  The bacterial flagellum contains a specialized secretion apparatus in its base that pumps certain protein subunits through the growing structure to their sites of installation beyond the membrane. A related apparatus functions in the injectisomes of gram-negative pathogens to export virulence factors into host cells. This mode of protein export is termed type-III secretion (T3S). Details of the T3S mechanism are unclear. It is energized by the proton gradient; here, a mutational approach was used to identify proton-binding groups that might function in transport. Conserved proton-binding residues in all the membrane components were tested. The results identify residues R147, R154 and D158 of FlhA as most critical. These lie in a small, well-conserved cytoplasmic domain of FlhA, located between transmembrane segments 4 and 5. Two-hybrid experiments demonstrate self-interaction of the domain, and targeted cross-linking indicates that it forms a multimeric array. A mutation that mimics protonation of the key acidic residue (D158N) was shown to trigger a global conformational change that affects the other, larger cytoplasmic domain that interacts with the export cargo. The results are discussed in the framework of a transport model based on proton-actuated movements in the cytoplasmic domains of FlhA.

• A flagellum-specific chaperone facilitates assembly of the core type III export apparatus of the bacterial flagellum

  2017

  PLoS Biology · 64 Zitationen · DOI

  Many bacteria move using a complex, self-assembling nanomachine, the bacterial flagellum. Biosynthesis of the flagellum depends on a flagellar-specific type III secretion system (T3SS), a protein export machine homologous to the export machinery of the virulence-associated injectisome. Six cytoplasmic (FliH/I/J/G/M/N) and seven integral-membrane proteins (FlhA/B FliF/O/P/Q/R) form the flagellar basal body and are involved in the transport of flagellar building blocks across the inner membrane in a proton motive force-dependent manner. However, how the large, multi-component transmembrane export gate complex assembles in a coordinated manner remains enigmatic. Specific for most flagellar T3SSs is the presence of FliO, a small bitopic membrane protein with a large cytoplasmic domain. The function of FliO is unknown, but homologs of FliO are found in >80% of all flagellated bacteria. Here, we demonstrate that FliO protects FliP from proteolytic degradation and promotes the formation of a stable FliP-FliR complex required for the assembly of a functional core export apparatus. We further reveal the subcellular localization of FliO by super-resolution microscopy and show that FliO is not part of the assembled flagellar basal body. In summary, our results suggest that FliO functions as a novel, flagellar T3SS-specific chaperone, which facilitates quality control and productive assembly of the core T3SS export machinery.

• Flagellin phase-dependent swimming on epithelial cell surfaces contributes to productive<i>Salmonella</i>gut colonisation

  2017

  Cellular Microbiology · 63 Zitationen · DOI

  The flagellum is a sophisticated nanomachine and an important virulence factor of many pathogenic bacteria. Flagellar motility enables directed movements towards host cells in a chemotactic process, and near-surface swimming on cell surfaces is crucial for selection of permissive entry sites. The long external flagellar filament is made of tens of thousands subunits of a single protein, flagellin, and many Salmonella serovars alternate expression of antigenically distinct flagellin proteins, FliC and FljB. However, the role of the different flagellin variants during gut colonisation and host cell invasion remains elusive. Here, we demonstrate that flagella made of different flagellin variants display structural differences and affect Salmonella's swimming behaviour on host cell surfaces. We observed a distinct advantage of bacteria expressing FliC-flagella to identify target sites on host cell surfaces and to invade epithelial cells. FliC-expressing bacteria outcompeted FljB-expressing bacteria for intestinal tissue colonisation in the gastroenteritis and typhoid murine infection models. Intracellular survival and responses of the host immune system were not altered. We conclude that structural properties of flagella modulate the swimming behaviour on host cell surfaces, which facilitates the search for invasion sites and might constitute a general mechanism for productive host cell invasion of flagellated bacteria.

• Engineered <i>Salmonella enterica</i> serovar Typhimurium overcomes limitations of anti-bacterial immunity in bacteria-mediated tumor therapy

  2017

  OncoImmunology · 63 Zitationen · DOI

  Cancer is one of the leading causes of death in the industrialized world and represents a tremendous social and economic burden. As conventional therapies fail to provide a sustainable cure for most cancer patients, the emerging unique immune therapeutic approach of bacteria-mediated tumor therapy (BMTT) is marching towards a feasible solution. Although promising results have been obtained with BMTT using various preclinical tumor models, for advancement a major concern is immunity against the bacterial vector itself. Pre-exposure to the therapeutic agent under field conditions is a reasonable expectation and may limit the therapeutic efficacy of BMTT. In the present study, we investigated the therapeutic potential of <i>Salmonella</i> and <i>E. coli</i> vector strains in naïve and immunized tumor bearing mice. Pre-exposure to the therapeutic agent caused a significant aberrant phenotype of the microenvironment of colonized tumors and limited the <i>in vivo</i> efficacy of established BMTT vector strains <i>Salmonella</i> SL7207 and <i>E. coli</i> Symbioflor-2. Using targeted genetic engineering, we generated the optimized auxotrophic <i>Salmonella</i> vector strain SF200 (<i>ΔlpxR9 ΔpagL7 ΔpagP8 ΔaroA ΔydiV ΔfliF</i>) harboring modifications in Lipid A and flagella synthesis. This combination of mutations resulted in an increased immune-stimulatory capacity and as such the strain was able to overcome the efficacy-limiting effects of pre-exposure. Thus, we conclude that any limitations of BMTT concerning anti-bacterial immunity may be countered by strategies that optimize the immune-stimulatory capacity of the attenuated vector strains.

• Regulatory principles governing Salmonella and Yersinia virulence

  2015

  Frontiers in Microbiology · 59 Zitationen · DOI

  Enteric pathogens such as Salmonella and Yersinia evolved numerous strategies to survive and proliferate in different environmental reservoirs and mammalian hosts. Deciphering common and pathogen-specific principles for how these bacteria adjust and coordinate spatiotemporal expression of virulence determinants, stress adaptation, and metabolic functions is fundamental to understand microbial pathogenesis. In order to manage sudden environmental changes, attacks by the host immune systems and microbial competition, the pathogens employ a plethora of transcriptional and post-transcriptional control elements, including transcription factors, sensory and regulatory RNAs, RNAses, and proteases, to fine-tune and control complex gene regulatory networks. Many of the contributing global regulators and the molecular mechanisms of regulation are frequently conserved between Yersinia and Salmonella. However, the interplay, arrangement, and composition of the control elements vary between these closely related enteric pathogens, which generate phenotypic differences leading to distinct pathogenic properties. In this overview we present common and different regulatory networks used by Salmonella and Yersinia to coordinate the expression of crucial motility, cell adhesion and invasion determinants, immune defense strategies, and metabolic adaptation processes. We highlight evolutionary changes of the gene regulatory circuits that result in different properties of the regulatory elements and how this influences the overall outcome of the infection process.

• Single molecule super-resolution imaging of proteins in living Salmonella enterica using self-labelling enzymes

  2016

  Scientific Reports · 58 Zitationen · DOI

  The investigation of the subcellular localization, dynamics and interaction of proteins and protein complexes in prokaryotes is complicated by the small size of the cells. Super-resolution microscopy (SRM) comprise various new techniques that allow light microscopy with a resolution that can be up to ten-fold higher than conventional light microscopy. Application of SRM techniques to living prokaryotes demands the introduction of suitable fluorescent probes, usually by fusion of proteins of interest to fluorescent proteins with properties compatible to SRM. Here we describe an approach that is based on the genetically encoded self-labelling enzymes HaloTag and SNAP-tag. Proteins of interest are fused to HaloTag or SNAP-tag and cell permeable substrates can be labelled with various SRM-compatible fluorochromes. Fusions of the enzyme tags to subunits of a type I secretion system (T1SS), a T3SS, the flagellar rotor and a transcription factor were generated and analysed in living Salmonella enterica. The new approach is versatile in tagging proteins of interest in bacterial cells and allows to determine the number, relative subcellular localization and dynamics of protein complexes in living cells.

• The role of the FliK molecular ruler in hook‐length control in <i>Salmonella enterica</i>

  2010

  Molecular Microbiology · 58 Zitationen · DOI

  A molecular ruler, FliK, controls the length of the flagellar hook. FliK measures hook length and catalyses the secretion-substrate specificity switch from rod-hook substrate specificity to late substrate secretion, which includes the filament subunits. Here, we show normal hook-length control and filament assembly in the complete absence of the C-ring thus refuting the previous 'cup' model for hook-length control. Mutants of C-ring components, which are reported to produce short hooks, show a reduced rate of hook-basal body assembly thereby allowing for a premature secretion-substrate specificity switch. Unlike fliK null mutants, hook-length control in an autocleavage-defective mutant of flhB, the protein responsible for the switch to late substrate secretion, is completely abolished. FliK deletion variants that retain the ability to measure hook length are secreted thus demonstrating that FliK directly measures rod-hook length during the secretion process. Finally, we present a unifying model accounting for all published data on hook-length control in which FliK acts as a molecular ruler that takes measurements of rod-hook length while being intermittently secreted during the assembly process of the hook-basal body complex.

• C‐ring requirement in flagellar type III secretion is bypassed by FlhDC upregulation

  2009

  Molecular Microbiology · 56 Zitationen · DOI

  The cytoplasmic C-ring of the flagellum consists of FliG, FliM and FliN and acts as an affinity cup to localize secretion substrates for protein translocation via the flagellar-specific type III secretion system. Random T-POP transposon mutagenesis was employed to screen for insertion mutants that allowed flagellar type III secretion in the absence of the C-ring using the flagellar type III secretion system-specific hook-beta-lactamase reporter (Lee and Hughes, 2006). Any condition resulting in at least a twofold increase in flhDC expression was sufficient to overcome the requirement for the C-ring and the ATPase complex FliHIJ in flagellar type III secretion. Insertions in known and unknown flagellar regulatory loci were isolated as well as chromosomal duplications of the flhDC region. The twofold increased flhDC mRNA level coincided in a twofold increase in the number of hook-basal bodies per cell as analysed by fluorescent microscopy. These results indicate that the C-ring functions as a nonessential affinity cup-like structure during flagellar type III secretion to enhance the specificity and efficiency of the secretion process.

• Hook length of the bacterial flagellum is optimized for maximal stability of the flagellar bundle

  2018

  PLoS Biology · 55 Zitationen · DOI

  Most bacteria swim in liquid environments by rotating one or several flagella. The long external filament of the flagellum is connected to a membrane-embedded basal body by a flexible universal joint, the hook, which allows the transmission of motor torque to the filament. The length of the hook is controlled on a nanometer scale by a sophisticated molecular ruler mechanism. However, why its length is stringently controlled has remained elusive. We engineered and studied a diverse set of hook-length variants of Salmonella enterica. Measurements of plate-assay motility, single-cell swimming speed, and directional persistence in quasi-2D and population-averaged swimming speed and body angular velocity in 3D revealed that the motility performance is optimal around the wild-type hook length. We conclude that too-short hooks may be too stiff to function as a junction and too-long hooks may buckle and create instability in the flagellar bundle. Accordingly, peritrichously flagellated bacteria move most efficiently as the distance travelled per body rotation is maximal and body wobbling is minimized. Thus, our results suggest that the molecular ruler mechanism evolved to control flagellar hook growth to the optimal length consistent with efficient bundle formation. The hook-length control mechanism is therefore a prime example of how bacteria evolved elegant but robust mechanisms to maximize their fitness under specific environmental constraints.

• Demokrit-Universität Thrakien

  Entscheidungsfindung von Zellen in multizellulären Systemen: Das 'Least microEnvironmental Uncertainty' Prinzip (LEUP)

  university

• Eberhard Karls Universität Tübingen

  Qualitätsmanagement während der Assemblierung von bakteriellen Typ-III Sekretionssystemen – eine vergleichende Studie des Aufbaus von Flagellen und Injektisomen

  university

• Helmholtz-Zentrum für Infektionsforschung

  Entscheidungsfindung von Zellen in multizellulären Systemen: Das 'Least microEnvironmental Uncertainty' Prinzip (LEUP)

  other

• Università degli Studi di Milano

  Entscheidungsfindung von Zellen in multizellulären Systemen: Das 'Least microEnvironmental Uncertainty' Prinzip (LEUP)

  university

• Universitätsklinikum Tübingen

  Qualitätsmanagement während der Assemblierung von bakteriellen Typ-III Sekretionssystemen – eine vergleichende Studie des Aufbaus von Flagellen und Injektisomen

  other

• Weizmann-Institut für Wissenschaften

  Entscheidungsfindung von Zellen in multizellulären Systemen: Das 'Least microEnvironmental Uncertainty' Prinzip (LEUP)

  research_institute

Name

Prof. Dr. Marc Erhardt

Titel

Prof. Dr.

Fakultät

Lebenswissenschaftliche Fakultät

Institut

Institut für Biologie

Arbeitsgruppe

Molekulare Mikrobiologie

Telefon

+49 30 2093-49780

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26.4.2026, 01:04:24