Regulation and function of Ag43 (flu).

Antigen 43 (Ag43) is an abundant outer membrane protein in Escherichia coli belonging to the autotransporter family. Structure-function relationships of Ag43 proposed on the basis of experimental work and in silico analysis are discussed in context of insights derived from molecular modeling. New sequence analysis sheds light on the phylogeny of the allelic variants of the Ag43-encoding gene and identifies two distinct families that appear to be distributed between specific pathogenic and commensal isolates. The molecular mechanism that controls expression by phase variation to create population heterogeneity is discussed. Proposed roles of Ag43 expression for E. coli are summarized and the studies are put into perspective regarding the role of allelic variants, genetic background of the bacterial strain, and control of expression by phase variation. We conclude that future studies need to take into account these variables to obtain a complete understanding of the contribution of Ag43 expression to E. coli biology.

[1]  H. Winkler,et al.  The role of energy coupling in the transport of beta-galactosides by Escherichia coli. , 1966, The Journal of biological chemistry.

[2]  P. Owen,et al.  Molecular structure of membrane vesicles from Escherichia coli. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[3]  B. Diderichsen.  flu, a metastable gene controlling surface properties of Escherichia coli , 1980, Journal of bacteriology.

[4]  I. Henderson,et al.  Phase-variable outer membrane proteins in Escherichia coli. , 1996, FEMS immunology and medical microbiology.

[5]  I. Henderson,et al.  Antigen 43, a phase-variable bipartite outer membrane protein, determines colony morphology and autoaggregation in Escherichia coli K-12. , 1997, FEMS microbiology letters.

[6]  I. Henderson,et al.  A novel regulatory mechanism for a novel phase-variable outer membrane protein of Escherichia coli. , 1997, Advances in Experimental Medicine and Biology.

[7]  I. Henderson,et al.  The Major Phase-Variable Outer Membrane Protein ofEscherichia coli Structurally Resembles the Immunoglobulin A1 Protease Class of Exported Protein and Is Regulated by a Novel Mechanism Involving Dam and OxyR , 1999, Journal of bacteriology.

[8]  H. Hasman,et al.  Antigen-43-Mediated Autoaggregation ofEscherichia coli Is Blocked by Fimbriation , 1999, Journal of bacteriology.

[9]  I. Henderson,et al.  Molecular switches — the ON and OFF of bacterial phase variation , 1999, Molecular microbiology.

[10]  H. Hasman,et al.  Antigen 43 from Escherichia coli Induces Inter- and Intraspecies Cell Aggregation and Changes in Colony Morphology of Pseudomonas fluorescens , 2000, Journal of bacteriology.

[11]  M. W. van der Woude,et al.  Phase variation of Ag43 in Escherichia coli: Dam‐dependent methylation abrogates OxyR binding and OxyR‐mediated repression of transcription , 2000, Molecular microbiology.

[12]  R. Kolter,et al.  The outer membrane protein, Antigen 43, mediates cell‐to‐cell interactions within Escherichia coli biofilms , 2000, Molecular microbiology.

[13]  K. Rajakumar,et al.  Ferric Dicitrate Transport System (Fec) of Shigella flexneri 2a YSH6000 Is Encoded on a Novel Pathogenicity Island Carrying Multiple Antibiotic Resistance Genes , 2001, Infection and Immunity.

[14]  E. Willery,et al.  Beta‐helix model for the filamentous haemagglutinin adhesin of Bordetella pertussis and related bacterial secretory proteins , 2001, Molecular microbiology.

[15]  J. McFadden,et al.  Antigen 43, the major phase-variable protein of the Escherichia coli outer membrane, can exist as a family of proteins encoded by multiple alleles. , 2001, Microbiology.

[16]  F. Blattner,et al.  Characterization of Cah, a calcium‐binding and heat‐extractable autotransporter protein of enterohaemorrhagic Escherichia coli , 2002, Molecular microbiology.

[17]  Vincent Munster,et al.  Dam‐dependent phase variation of Ag43 in Escherichia coli is altered in a seqA mutant , 2002, Molecular microbiology.

[18]  Denise E. Waldron,et al.  Competitive interaction of the OxyR DNA‐binding protein and the Dam methylase at the antigen 43 gene regulatory region in Escherichia coli , 2002, Molecular microbiology.

[19]  Yufeng Zhai,et al.  Protein-translocating outer membrane porins of Gram-negative bacteria. , 2002, Biochimica et biophysica acta.

[20]  M. W. van der Woude,et al.  Dam- and OxyR-Dependent Phase Variation of agn43: Essential Elements and Evidence for a New Role of DNA Methylation , 2002, Journal of bacteriology.

[21]  D. Ussery,et al.  DNA microarray analysis of fim mutations in Escherichia coli , 2002, Molecular Genetics and Genomics.

[22]  S. Hultgren,et al.  Intracellular Bacterial Biofilm-Like Pods in Urinary Tract Infections , 2003, Science.

[23]  D. Clarke,et al.  The RcsC sensor kinase is required for normal biofilm formation in Escherichia coli K‐12 and controls the expression of a regulon in response to growth on a solid surface , 2003, Molecular microbiology.

[24]  M. Urbanus,et al.  Signal Recognition Particle (SRP)-mediated Targeting and Sec-dependent Translocation of an Extracellular Escherichia coli Protein* , 2003, The Journal of Biological Chemistry.

[25]  M. W. van der Woude,et al.  Phase Variation of Ag43 Is Independent of the Oxidation State of OxyR , 2002, Journal of bacteriology.

[26]  M. Schembri,et al.  Global gene expression in Escherichia coli biofilms , 2003, Molecular microbiology.

[27]  R. Fernandez,et al.  A conserved region within the Bordetella pertussis autotransporter BrkA is necessary for folding of its passenger domain , 2003, Molecular microbiology.

[28]  M. W. van der Woude,et al.  Phase and Antigenic Variation in Bacteria , 2004, Clinical Microbiology Reviews.

[29]  K. Rajakumar,et al.  Role of attP in Integrase-Mediated Integration of the Shigella Resistance Locus Pathogenicity Island of Shigella flexneri , 2004, Antimicrobial Agents and Chemotherapy.

[30]  C. Beinke,et al.  Modular organization of the AIDA autotransporter translocator: The N-terminal β1-domain is surface-exposed and stabilizes the transmembrane β2-domain , 2001, Antonie van Leeuwenhoek.

[31]  M. Schembri,et al.  Structure‐function analysis of the self‐recognizing Antigen 43 autotransporter protein from Escherichia coli , 2003, Molecular microbiology.

[32]  D. Gally,et al.  Switches, cross-talk and memory in Escherichia coli adherence. , 2004, Journal of medical microbiology.

[33]  K. Rajakumar,et al.  Regulated site‐specific recombination of the she pathogenicity island of Shigella flexneri , 2004, Molecular microbiology.

[34]  J. Ghigo,et al.  Combined Inactivation and Expression Strategy To Study Gene Function under Physiological Conditions: Application to Identification of New Escherichia coli Adhesins , 2005, Journal of bacteriology.

[35]  N. Høiby,et al.  Biological Trojan Horse: Antigen 43 Provides Specific Bacterial Uptake and Survival in Human Neutrophils , 2006, Infection and Immunity.

[36]  A. V. McDonnell,et al.  Pertactin beta-helix folding mechanism suggests common themes for the secretion and folding of autotransporter proteins. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[37]  Kai Michaelis,et al.  The Transcriptional Antiterminator RfaH Represses Biofilm Formation in Escherichia coli , 2006, Journal of bacteriology.

[38]  Thomas K. Wood,et al.  Autoinducer 2 Controls Biofilm Formation in Escherichia coli through a Novel Motility Quorum-Sensing Regulator (MqsR, B3022) , 2006, Journal of bacteriology.

[39]  H. Mobley,et al.  Role of Phase Variation of Type 1 Fimbriae in a Uropathogenic Escherichia coli Cystitis Isolate during Urinary Tract Infection , 2006, Infection and Immunity.

[40]  J. Tommassen,et al.  Polar Localization of the Autotransporter Family of Large Bacterial Virulence Proteins , 2006, Journal of bacteriology.

[41]  U. Dobrindt,et al.  Glycosylation of the Self-Recognizing Escherichia coli Ag43 Autotransporter Protein , 2006, Journal of bacteriology.

[42]  Thomas K. Wood,et al.  YdgG (TqsA) Controls Biofilm Formation in Escherichia coli K-12 through Autoinducer 2 Transport , 2006, Journal of bacteriology.

[43]  Andrey V Kajava,et al.  The turn of the screw: variations of the abundant beta-solenoid motif in passenger domains of Type V secretory proteins. , 2006, Journal of structural biology.

[44]  H. Bernstein,et al.  An Unusual Signal Peptide Extension Inhibits the Binding of Bacterial Presecretory Proteins to the Signal Recognition Particle, Trigger Factor, and the SecYEG Complex* , 2006, Journal of Biological Chemistry.

[45]  M. W. Woude,et al.  Re-examining the role and random nature of phase variation , 2006 .

[46]  G. Ulett,et al.  Antigen-43-mediated autoaggregation impairs motility in Escherichia coli. , 2006, Microbiology.

[47]  M. W. van der Woude.  Re-examining the role and random nature of phase variation. , 2006, FEMS microbiology letters.

[48]  S. Gottesman,et al.  Remodelling of the Escherichia coli outer membrane by two small regulatory RNAs , 2006, Molecular microbiology.

[49]  S. Buchanan,et al.  Autotransporter structure reveals intra-barrel cleavage followed by conformational changes , 2007, Nature Structural &Molecular Biology.

[50]  C. Dozois,et al.  Autotransporter-Encoding Sequences Are Phylogenetically Distributed among Escherichia coli Clinical Isolates and Reference Strains , 2007, Applied and Environmental Microbiology.

[51]  Han N. Lim,et al.  A multistep epigenetic switch enables the stable inheritance of DNA methylation states , 2007, Nature Genetics.

[52]  Functional organization of the autotransporter adhesin involved in diffuse adherence. , 2007, Journal of bacteriology.

[53]  The multicopper oxidase (CueO) and cell aggregation in Escherichia coli. , 2007, Environmental microbiology.

[54]  G. Ulett,et al.  Autotransporter proteins: novel targets at the bacterial cell surface. , 2007, FEMS microbiology letters.

[55]  H. Bernstein,et al.  Protein secretion in gram-negative bacteria via the autotransporter pathway. , 2007, Annual review of microbiology.

[56]  D. E. Anderson,et al.  Cleavage of a bacterial autotransporter by an evolutionarily convergent autocatalytic mechanism , 2007, The EMBO journal.

[57]  J. Valle,et al.  Functional Analysis of Antigen 43 in Uropathogenic Escherichia coli Reveals a Role in Long-Term Persistence in the Urinary Tract , 2007, Infection and Immunity.

[58]  H. Mobley,et al.  Uropathogenic Escherichia coli Outer Membrane Antigens Expressed during Urinary Tract Infection , 2007, Infection and Immunity.

[59]  F. Lépine,et al.  O-Linked Glycosylation Ensures the Normal Conformation of the Autotransporter Adhesin Involved in Diffuse Adherence , 2007, Journal of bacteriology.

[60]  I. Henderson,et al.  The Escherichia coli biofilm-promoting protein Antigen 43 does not contribute to intestinal colonization. , 2008, FEMS microbiology letters.

[61]  D. Otzen,et al.  Effect of glycosylation on the extracellular domain of the Ag43 bacterial autotransporter: enhanced stability and reduced cellular aggregation. , 2008, The Biochemical journal.