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Journal articleFilloux A, Whitfield C, 2016,
Editorial: The many wonders of the bacterial cell surface
, FEMS MICROBIOLOGY REVIEWS, Vol: 40, Pages: 161-163, ISSN: 0168-6445- Author Web Link
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- Citations: 9
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Journal articleSerrano M, Crawshaw AD, Dembek M, et al., 2016,
The SpoIIQ-SpoIIIAH complex of Clostridium difficile controls forespore engulfment and late stages of gene expression and spore morphogenesis
, Molecular Microbiology, Vol: 100, Pages: 204-228, ISSN: 1365-2958Engulfment of the forespore by the mother cell is a universal feature of endosporulation. In Bacillus subtilis, the forespore protein SpoIIQ and the mother cell protein SpoIIIAH form a channel, essential for endosporulation, through which the developing spore is nurtured. The two proteins also form a backup system for engulfment. Unlike in B. subtilis, SpoIIQ of Clostridium difficile has intact LytM zinc-binding motifs. We show that spoIIQ or spoIIIAH deletion mutants of C. difficile result in anomalous engulfment, and that disruption of the SpoIIQ LytM domain via a single amino acid substitution (H120S) impairs engulfment differently. SpoIIQ and SpoIIQH120S interact with SpoIIIAH throughout engulfment. SpoIIQ, but not SpoIIQH120S, binds Zn2+, and metal absence alters the SpoIIQ-SpoIIIAH complex in vitro. Possibly, SpoIIQH120S supports normal engulfment in some cells but not a second function of the complex, required following engulfment completion. We show that cells of the spoIIQ or spoIIIAH mutants that complete engulfment are impaired in post-engulfment, forespore and mother cell-specific gene expression, suggesting a channel-like function. Both engulfment and a channel-like function may be ancestral functions of SpoIIQ-SpoIIIAH while the requirement for engulfment was alleviated through the emergence of redundant mechanisms in B. subtilis and related organisms.
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Journal articleFisher RA, Cheverton AM, Helaine S, 2016,
Analysis of Macrophage-Induced Salmonella Persisters.
, Methods in Molecular Biology, Vol: 1333, Pages: 177-187, ISSN: 1940-6029A 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.
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Journal articleTaylor J, Taylor G, Hare S, et al., 2016,
Structures of the DfsB protein family suggest a cationic, helical sibling-lethal factor peptide
, Journal of Molecular Biology, Vol: 428, Pages: 554-560, ISSN: 1089-8638Bacteria have developed a variety of mechanisms for survivingharsh environmental conditions, nutrient stress and overpopulation.Paenibacillus dendritiformis produces a lethal protein (Slf) that is ableto induce cell death in neighboring colonies and a phenotypic switch inmore distant ones. Slf is derived from the secreted precursor protein,DfsB, after proteolytic processing. Here, we present new crystalstructures of DfsB homologues from a variety of bacterial species and asurprising version present in the yeast Saccharomyces cerevisiae.Adopting a four-helix bundle decorated with a further three short heliceswithin intervening loops, DfsB belongs to a non-enzymatic class of theDinB fold. The structure suggests that the biologically-active Slffragment may possess a C-terminal helix rich in basic and aromaticresidues that suggest a functional mechanism akin to that for cationicantimicrobial peptides.
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Journal articleKlionsky DJ, Abdelmohsen K, Abe A, et al., 2016,
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
, Autophagy, Vol: 12, Pages: 1-215, ISSN: 1554-8635 -
Journal articleLeen EN, Sorgeloos F, Correia S, et al., 2016,
A conserved interaction between a C-terminal motif in norovirus VPg and the HEAT-1 domain of eIF4G is essential for translation initiation
, PLOS Pathogens, Vol: 12, ISSN: 1553-7366Translation initiation is a critical early step in the replication cycle of the positive-sense, single-stranded RNA genome of noroviruses, a major cause of gastroenteritis in humans. Norovirus RNA, which has neither a 5´ m7G cap nor an internal ribosome entry site (IRES), adopts an unusual mechanism to initiate protein synthesis that relies on interactions between the VPg protein covalently attached to the 5´-end of the viral RNA and eukaryotic initiation factors (eIFs) in the host cell. For murine norovirus (MNV) we previously showed that VPg binds to the middle fragment of eIF4G (4GM; residues 652-1132). Here we have used pull-down assays, fluorescence anisotropy, and isothermal titration calorimetry (ITC) to demonstrate that a stretch of ~20 amino acids at the C terminus of MNV VPg mediates direct and specific binding to the HEAT-1 domain within the 4GM fragment of eIF4G. Our analysis further reveals that the MNV C terminus binds to eIF4G HEAT-1 via a motif that is conserved in all known noroviruses. Fine mutagenic mapping suggests that the MNV VPg C terminus may interact with eIF4G in a helical conformation. NMR spectroscopy was used to define the VPg binding site on eIF4G HEAT-1, which was confirmed by mutagenesis and binding assays. We have found that this site is non-overlapping with the binding site for eIF4A on eIF4G HEAT-1 by demonstrating that norovirus VPg can form ternary VPg-eIF4G-eIF4A complexes. The functional significance of the VPg-eIF4G interaction was shown by the ability of fusion proteins containing the C-terminal peptide of MNV VPg to inhibit in vitro translation of norovirus RNA but not cap- or IRES-dependent translation. These observations define important structural details of a functional interaction between norovirus VPg and eIF4G and reveal a binding interface that might be exploited as a target for antiviral therapy.
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Journal articlefilloux A, wood TE, Hachani A, 2015,
Type VI secretion and anti-host effectors.
, Current Opinion in Microbiology, ISSN: 1879-0364 -
Journal articleComas I, Hailu E, Kiros T, et al., 2015,
Population Genomics of Mycobacterium tuberculosis in Ethiopia Contradicts the Virgin Soil Hypothesis for Human Tuberculosis in Sub-Saharan Africa
, Current Biology, Vol: 25, Pages: 3260-3266, ISSN: 1879-0445Colonial medical reports claimed that tuberculosis (TB) was largely unknown in Africa prior to European contact, providing a “virgin soil” for spread of TB in highly susceptible populations previously unexposed to the disease [1 and 2]. This is in direct contrast to recent phylogenetic models which support an African origin for TB [3, 4, 5 and 6]. To address this apparent contradiction, we performed a broad genomic sampling of Mycobacterium tuberculosis in Ethiopia. All members of the M. tuberculosis complex (MTBC) arose from clonal expansion of a single common ancestor [ 7] with a proposed origin in East Africa [ 3, 4 and 8]. Consistent with this proposal, MTBC lineage 7 is almost exclusively found in that region [ 9, 10 and 11]. Although a detailed medical history of Ethiopia supports the view that TB was rare until the 20th century [12], over the last century Ethiopia has become a high-burden TB country [13]. Our results provide further support for an African origin for TB, with some genotypes already present on the continent well before European contact. Phylogenetic analyses reveal a pattern of serial introductions of multiple genotypes into Ethiopia in association with human migration and trade. In place of a “virgin soil” fostering the spread of TB in a previously naive population, we propose that increased TB mortality in Africa was driven by the introduction of European strains of M. tuberculosis alongside expansion of selected indigenous strains having biological characteristics that carry a fitness benefit in the urbanized settings of post-colonial Africa.
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Journal articleFairweather NF, Willing SE, Richards EJ, et al., 2015,
Increased toxin expression in a Clostridium difficile mfd mutant
, BMC Microbiology, ISSN: 1471-2180 -
Journal articleWong CT, Xu Y, Gupta A, et al., 2015,
Structural analysis of haemoglobin binding by HpuA from the Neisseriaceae family
, Nature Communications, Vol: 6, ISSN: 2041-1723The Neisseriaceae family of bacteria causes a range of diseases including meningitis, septicaemia, gonorrhoea and endocarditis, and extracts haem from haemoglobin as an important iron source within the iron-limited environment of its human host. Herein we report crystal structures of apo- and haemoglobin-bound HpuA, an essential component of this haem import system. The interface involves long loops on the bacterial receptor that present hydrophobic side chains for packing against the surface of haemoglobin. Interestingly, our structural and biochemical analyses of Kingella denitrificans and Neisseria gonorrhoeae HpuA mutants, although validating the interactions observed in the crystal structure, show how Neisseriaceae have the fascinating ability to diversify functional sequences and yet retain the haemoglobin binding function. Our results present the first description of HpuA’s role in direct binding of haemoglobin.
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