25 results found
Rycroft JA, Gollan B, Grabe GJ, et al., 2018, Activity of acetyltransferase toxins involved in Salmonella persister formation during macrophage infection, NATURE COMMUNICATIONS, Vol: 9, ISSN: 2041-1723
Wilcox B, Osterman I, Serebryakova M, et al., 2018, Escherichia coli ItaT is a type II toxin that inhibits translation by acetylating isoleucyl-tRNAIle., Nucleic Acids Res
Prokaryotic toxin-antitoxin (TA) modules are highly abundant and are involved in stress response and drug tolerance. The most common type II TA modules consist of two interacting proteins. The type II toxins are diverse enzymes targeting various essential intracellular targets. The antitoxin binds to cognate toxin and inhibits its function. Recently, TA modules whose toxins are GNAT-family acetyltransferases were described. For two such systems, the target of acetylation was shown to be aminoacyl-tRNA: the TacT toxin targets aminoacylated elongator tRNAs, while AtaT targets the amino acid moiety of initiating tRNAMet. We show that the itaRT gene pair from Escherichia coli encodes a TA module with acetyltransferase toxin ItaT that specifically and exclusively acetylates Ile-tRNAIle thereby blocking translation and inhibiting cell growth. ItaT forms a tight complex with the ItaR antitoxin, which represses the transcription of itaRT operon. A comprehensive bioinformatics survey of GNAT acetyltransferases reveals that enzymes encoded by validated or putative TA modules are common and form a distinct branch of the GNAT family tree. We speculate that further functional analysis of such TA modules will result in identification of enzymes capable of specifically targeting many, perhaps all, aminoacyl tRNAs.
Fisher RA, Gollan B, Helaine S, 2017, Persistent bacterial infections and persister cells, NATURE REVIEWS MICROBIOLOGY, Vol: 15, Pages: 453-464, ISSN: 1740-1526
Hall AMJ, Gollan B, Helaine S, 2017, Toxin-antitoxin systems: reversible toxicity, CURRENT OPINION IN MICROBIOLOGY, Vol: 36, Pages: 102-110, ISSN: 1369-5274
Saliba A-E, Li L, Westermann AJ, et al., 2017, Single-cell RNA-seq ties macrophage polarization to growth rate of intracellular Salmonella, NATURE MICROBIOLOGY, Vol: 2, ISSN: 2058-5276
Cheverton AM, Gollan B, Przydacz M, et al., 2016, A Salmonella Toxin Promotes Persister Formation through Acetylation of tRNA., Molecular cell, Vol: 63, Pages: 86-96, ISSN: 1097-2765
The recalcitrance of many bacterial infections to antibiotic treatment is thought to be due to the presence of persisters that are non-growing, antibiotic-insensitive cells. Eventually, persisters resume growth, accounting for relapses of infection. Salmonella is an important pathogen that causes disease through its ability to survive inside macrophages. After macrophage phagocytosis, a significant proportion of the Salmonella population forms non-growing persisters through the action of toxin-antitoxin modules. Here we reveal that one such toxin, TacT, is an acetyltransferase that blocks the primary amine group of amino acids on charged tRNA molecules, thereby inhibiting translation and promoting persister formation. Furthermore, we report the crystal structure of TacT and note unique structural features, including two positively charged surface patches that are essential for toxicity. Finally, we identify a detoxifying mechanism in Salmonella wherein peptidyl-tRNA hydrolase counteracts TacT-dependent growth arrest, explaining how bacterial persisters can resume growth.
Fisher RA, Cheverton AM, Helaine S, 2016, Analysis of Macrophage-Induced Salmonella Persisters., Methods Mol Biol, Vol: 1333, Pages: 177-187
A small subpopulation of non-replicating, multidrug-tolerant bacteria is present within clonal populations of many bacterial species. Known as persisters, these bacteria are probably the cause of relapsing infections such as typhoid fever. Formation of non-growing Salmonella persisters is stimulated by macrophage phagocytosis. This chapter outlines methods to identify and study persisters resulting from interactions between bacterial pathogens and their hosts. We use their antibiotic tolerance for isolation and enumeration and developed a method to study the heterogeneity of growth within clonal populations through single-cell analysis.
Mouton JM, Helaine S, Holden DW, et al., 2016, Elucidating population-wide mycobacterial replication dynamics at the single-cell level, MICROBIOLOGY-SGM, Vol: 162, Pages: 966-978, ISSN: 1350-0872
Santos AJM, Durkin CH, Helaine S, et al., 2016, Clustered Intracellular Salmonella enterica Serovar Typhimurium Blocks Host Cell Cytokinesis, INFECTION AND IMMUNITY, Vol: 84, Pages: 2149-2158, ISSN: 0019-9567
Figueira R, Brown DR, Ferreira D, et al., 2015, Adaptation to sustained nitrogen starvation by Escherichia coli requires the eukaryote-like serine/threonine kinase YeaG, SCIENTIFIC REPORTS, Vol: 5, ISSN: 2045-2322
Caly DL, Coulthurst SJ, An S-Q, et al., 2014, Communication, Cooperation, and Social Interactions: a Report from the Third Young Microbiologists Symposium on Microbe Signalling, Organisation, and Pathogenesis, JOURNAL OF BACTERIOLOGY, Vol: 196, Pages: 3527-3533, ISSN: 0021-9193
Helaine S, Cheverton AM, Watson KG, et al., 2014, Internalization of Salmonella by Macrophages Induces Formation of Nonreplicating Persisters, SCIENCE, Vol: 343, Pages: 204-208, ISSN: 0036-8075
Helaine S, Kugelberg E, 2014, Bacterial persisters: formation, eradication, and experimental systems, TRENDS IN MICROBIOLOGY, Vol: 22, Pages: 417-424, ISSN: 0966-842X
Figueira R, Watson KG, Holden DW, et al., 2013, Identification of Salmonella Pathogenicity Island-2 Type III Secretion System Effectors Involved in Intramacrophage Replication of S. enterica Serovar Typhimurium: Implications for Rational Vaccine Design, MBIO, Vol: 4, ISSN: 2150-7511
Helaine S, Holden DW, 2013, Heterogeneity of intracellular replication of bacterial pathogens, CURRENT OPINION IN MICROBIOLOGY, Vol: 16, Pages: 184-191, ISSN: 1369-5274
Thompson JA, Liu M, Helainet S, et al., 2011, Contribution of the PhoP/Q regulon to survival and replication of Salmonella enterica serovar Typhimurium in macrophages, MICROBIOLOGY-SGM, Vol: 157, Pages: 2084-2093, ISSN: 1350-0872
Brown DR, Helaine S, Carbonnelle E, et al., 2010, Systematic Functional Analysis Reveals That a Set of Seven Genes Is Involved in Fine-Tuning of the Multiple Functions Mediated by Type IV Pili in Neisseria meningitidis, INFECTION AND IMMUNITY, Vol: 78, Pages: 3053-3063, ISSN: 0019-9567
Helaine S, Thompson JA, Watson KG, et al., 2010, Dynamics of intracellular bacterial replication at the single cell level, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 107, Pages: 3746-3751, ISSN: 0027-8424
Thompson JA, Helaine S, Holden DW, 2010, The Salmonella-mouse interaction: a versatile model to study bacterial infection. Book chapter in "Bacterial virulence: basic principles, models and global approaches, Editors: Sansonetti
Helaine S, Dyer DH, Nassif X, et al., 2007, 3D structure/function analysis of PiIX reveals how minor pilins can modulate the virulence properties of type IV pili, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 104, Pages: 15888-15893, ISSN: 0027-8424
Carbonelle E, Helaine S, Nassif X, et al., 2006, A systematic genetic analysis in Neisseria meningitidis defines the Pil proteins required for assembly, functionality, stabilization and export of type IV pili, Molecular Microbiology, Pages: 1510-1522
Carbonnelle E, Helaine S, Nassif X, et al., 2006, A systematic genetic analysis in Neisseria meningitidis defines the Pil proteins required for assembly, functionality, stabilization and export of type IV pili, MOLECULAR MICROBIOLOGY, Vol: 61, Pages: 1510-1522, ISSN: 0950-382X
Carbonelle E, Helaine S, Prouvensier L, et al., 2005, Type IV pilus biogenesis in Neisseria meningitidis : PilW is involved in a step occurring after pilus assembly, essential for fibre stability and function, Molecular Microbiology
Carbonnelle E, Helaine S, Prouvensier L, et al., 2005, Type IV pilus biogenesis in Neisseria meningitidis: PilW is involved in a step occurring after pilus assembly, essential for fibre stability and function, MOLECULAR MICROBIOLOGY, Vol: 55, Pages: 54-64, ISSN: 0950-382X
Helaine S, Carbonnelle E, Prouvensier L, et al., 2005, PilX, a pilus-associated protein essential for bacterial aggregation, is a key to pilus-facilitated attachment of Neisseria meningitidis to human cells, MOLECULAR MICROBIOLOGY, Vol: 55, Pages: 65-77, ISSN: 0950-382X
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