Molecular and cellular insight into Escherichia coli SslE and its role during biofilm maturation.


Journal

NPJ biofilms and microbiomes
ISSN: 2055-5008
Titre abrégé: NPJ Biofilms Microbiomes
Pays: United States
ID NLM: 101666944

Informations de publication

Date de publication:
25 02 2022
Historique:
received: 31 03 2021
accepted: 31 01 2022
entrez: 26 2 2022
pubmed: 27 2 2022
medline: 1 4 2022
Statut: epublish

Résumé

Escherichia coli is a Gram-negative bacterium that colonises the human intestine and virulent strains can cause severe diarrhoeal and extraintestinal diseases. The protein SslE is secreted by a range of pathogenic and commensal E. coli strains. It can degrade mucins in the intestine, promotes biofilm maturation and it is a major determinant of infection in virulent strains, although how it carries out these functions is not well understood. Here, we examine SslE from the commensal E. coli Waksman and BL21 (DE3) strains and the enterotoxigenic H10407 and enteropathogenic E2348/69 strains. We reveal that SslE has a unique and dynamic structure in solution and in response to acidification within mature biofilms it can form a unique aggregate with amyloid-like properties. Furthermore, we show that both SslE monomers and aggregates bind DNA in vitro and co-localise with extracellular DNA (eDNA) in mature biofilms, and SslE aggregates may also associate with cellulose under certain conditions. Our results suggest that interactions between SslE and eDNA are important for biofilm maturation in many E. coli strains and SslE may also be a factor that drives biofilm formation in other SslE-secreting bacteria.

Identifiants

pubmed: 35217675
doi: 10.1038/s41522-022-00272-5
pii: 10.1038/s41522-022-00272-5
pmc: PMC8881592
doi:

Substances chimiques

Escherichia coli Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

9

Subventions

Organisme : Wellcome Trust
ID : SBF002/1150
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001029
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U117533887
Pays : United Kingdom
Organisme : Arthritis Research UK
ID : FC001029
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001029
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R017662/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : British Heart Foundation
ID : IG/16/2/32273
Pays : United Kingdom

Informations de copyright

© 2022. The Author(s).

Références

Kaper, J. B., Nataro, J. P. & Mobley, H. L. Pathogenic Escherichia coli. Nat. Rev. Microbiol 2, 123–140 (2004).
pubmed: 15040260 doi: 10.1038/nrmicro818
Gu, S., Shevchik, V. E., Shaw, R., Pickersgill, R. W. & Garnett, J. A. The role of intrinsic disorder and dynamics in the assembly and function of the type II secretion system. Biochim Biophys. Acta Proteins Proteom. 1865, 1255–1266 (2017).
pubmed: 28733198 doi: 10.1016/j.bbapap.2017.07.006
Moriel, D. G. et al. Identification of protective and broadly conserved vaccine antigens from the genome of extraintestinal pathogenic Escherichia coli. Proc. Natl Acad. Sci. USA 107, 9072–9077 (2010).
pubmed: 20439758 pmcid: 2889118 doi: 10.1073/pnas.0915077107
Baldi, D. L. et al. The type II secretion system and its ubiquitous lipoprotein substrate, SslE, are required for biofilm formation and virulence of enteropathogenic Escherichia coli. Infect. Immun. 80, 2042–2052 (2012).
pubmed: 22451516 pmcid: 3370571 doi: 10.1128/IAI.06160-11
Decanio, M. S., Landick, R. & Haft, R. J. The non-pathogenic Escherichia coli strain W secretes SslE via the virulence-associated type II secretion system beta. BMC Microbiol. 13, 130 (2013).
pubmed: 23758679 pmcid: 3707838 doi: 10.1186/1471-2180-13-130
Nesta, B. et al. SslE elicits functional antibodies that impair in vitro mucinase activity and in vivo colonization by both intestinal and extraintestinal Escherichia coli strains. PLoS Pathog. 10, e1004124 (2014).
pubmed: 24809621 pmcid: 4014459 doi: 10.1371/journal.ppat.1004124
Yang, J., Baldi, D. L., Tauschek, M., Strugnell, R. A. & Robins-Browne, R. M. Transcriptional regulation of the yghJ-pppA-yghG-gspCDEFGHIJKLM cluster, encoding the type II secretion pathway in enterotoxigenic Escherichia coli. J. Bacteriol. 189, 142–150 (2007).
pubmed: 17085567 doi: 10.1128/JB.01115-06
Naili, I. et al. Mixed mucosal-parenteral immunizations with the broadly conserved pathogenic Escherichia coli antigen SslE induce a robust mucosal and systemic immunity without affecting the murine intestinal microbiota. Vaccine 37, 314–324 (2019).
pubmed: 30503655 doi: 10.1016/j.vaccine.2018.10.008
Luo, Q. et al. Conservation and immunogenicity of novel antigens in diverse isolates of enterotoxigenic Escherichia coli. PLoS Negl. Trop. Dis. 9, e0003446 (2015).
pubmed: 25629897 pmcid: 4309559 doi: 10.1371/journal.pntd.0003446
Valeri, M. et al. Pathogenic E. coli exploits SslE mucinase activity to translocate through the mucosal barrier and get access to host cells. PLoS ONE 10, e0117486 (2015).
pubmed: 25789808 pmcid: 4366376 doi: 10.1371/journal.pone.0117486
Luo, Q. et al. Enterotoxigenic Escherichia coli secretes a highly conserved mucin-degrading metalloprotease to effectively engage intestinal epithelial cells. Infect. Immun. 82, 509–521 (2014).
pubmed: 24478067 pmcid: 3911403 doi: 10.1128/IAI.01106-13
Rehman, S. et al. Structure and functional analysis of the Legionella pneumophila chitinase ChiA reveals a novel mechanism of metal-dependent mucin degradation. PLoS Pathog. 16, e1008342 (2020).
pubmed: 32365117 pmcid: 7224574 doi: 10.1371/journal.ppat.1008342
Corfield, A. P. Mucins: a biologically relevant glycan barrier in mucosal protection. Biochim Biophys. Acta 1850, 236–252 (2015).
pubmed: 24821013 doi: 10.1016/j.bbagen.2014.05.003
Garnett, J. A. & Matthews, S. Interactions in bacterial biofilm development: a structural perspective. Curr. Protein Pept. Sci. 13, 739–755 (2012).
pubmed: 23305361 pmcid: 3601411 doi: 10.2174/138920312804871166
Vogeleer, P., Tremblay, Y. D., Mafu, A. A., Jacques, M. & Harel, J. Life on the outside: role of biofilms in environmental persistence of Shiga-toxin producing Escherichia coli. Front. Microbiol. 5, 317 (2014).
pubmed: 25071733 pmcid: 4076661 doi: 10.3389/fmicb.2014.00317
Chitlapilly Dass, S. et al. Impact of mixed biofilm formation with environmental microorganisms on E. coli O157:H7 survival against sanitization. npj Sci. Food 4, 16 (2020).
pubmed: 33083548 pmcid: 7560865 doi: 10.1038/s41538-020-00076-x
Rossi, E. et al. “It’s a gut feeling”—Escherichia coli biofilm formation in the gastrointestinal tract environment. Crit. Rev. Microbiol. 44, 1–30 (2018).
pubmed: 28485690 doi: 10.1080/1040841X.2017.1303660
Nakjang, S., Ndeh, D. A., Wipat, A., Bolam, D. N. & Hirt, R. P. A novel extracellular metallopeptidase domain shared by animal host-associated mutualistic and pathogenic microbes. PLoS ONE 7, e30287 (2012).
pubmed: 22299034 pmcid: 3267712 doi: 10.1371/journal.pone.0030287
Noach, I. et al. Recognition of protein-linked glycans as a determinant of peptidase activity. Proc. Natl Acad. Sci. USA 114, E679–E688 (2017).
pubmed: 28096352 pmcid: 5293097 doi: 10.1073/pnas.1615141114
Trastoy, B., Naegeli, A., Anso, I., Sjogren, J. & Guerin, M. E. Structural basis of mammalian mucin processing by the human gut O-glycopeptidase OgpA from Akkermansia muciniphila. Nat. Commun. 11, 4844 (2020).
pubmed: 32973204 pmcid: 7518263 doi: 10.1038/s41467-020-18696-y
Buchan, D. W. A. & Jones, D. T. The PSIPRED protein analysis workbench: 20 years on. Nucleic Acids Res. 47, W402–W407 (2019).
pubmed: 31251384 pmcid: 6602445 doi: 10.1093/nar/gkz297
Taglialegna, A., Lasa, I. & Valle, J. Amyloid structures as biofilm matrix scaffolds. J. Bacteriol. 198, 2579–2588 (2016).
pubmed: 27185827 pmcid: 5019065 doi: 10.1128/JB.00122-16
Belousov, M. V. et al. M60-like metalloprotease domain of the Escherichia coli YghJ protein forms amyloid fibrils. PLoS ONE 13, e0191317 (2018).
pubmed: 29381728 pmcid: 5790219 doi: 10.1371/journal.pone.0191317
Taglialegna, A. et al. The biofilm-associated surface protein Esp of Enterococcus faecalis forms amyloid-like fibers. npj Biofilms Microbiomes 6, 15 (2020).
pubmed: 32221298 pmcid: 7101364 doi: 10.1038/s41522-020-0125-2
Taglialegna, A. et al. Staphylococcal Bap proteins build amyloid scaffold biofilm matrices in response to environmental signals. PLoS Pathog. 12, e1005711 (2016).
pubmed: 27327765 pmcid: 4915627 doi: 10.1371/journal.ppat.1005711
Chen, D. et al. Characteristics and influencing factors of amyloid fibers in S. mutans biofilm. AMB Express 9, 31 (2019).
pubmed: 30820691 pmcid: 6395465 doi: 10.1186/s13568-019-0753-1
Gallardo, R., Ranson, N. A. & Radford, S. E. Amyloid structures: much more than just a cross-beta fold. Curr. Opin. Struct. Biol. 60, 7–16 (2020).
pubmed: 31683043 doi: 10.1016/j.sbi.2019.09.001
Moran, S. D. & Zanni, M. T. How to get insight into amyloid structure and formation from infrared spectroscopy. J. Phys. Chem. Lett. 5, 1984–1993 (2014).
pubmed: 24932380 pmcid: 4051309 doi: 10.1021/jz500794d
Conway, K. A., Harper, J. D. & Lansbury, P. T. Jr. Fibrils formed in vitro from alpha-synuclein and two mutant forms linked to Parkinson’s disease are typical amyloid. Biochemistry 39, 2552–2563 (2000).
pubmed: 10704204 doi: 10.1021/bi991447r
Herranz-Trillo, F. et al. Structural analysis of multi-component amyloid systems by chemometric SAXS data decomposition. Structure 25, 5–15 (2017).
pubmed: 27889205 doi: 10.1016/j.str.2016.10.013
Sagar, A., Herranz-Trillo, F., Langkilde, A. E., Vestergaard, B. & Bernado, P. Structure and thermodynamics of transient protein-protein complexes by chemometric decomposition of SAXS datasets. Structure 29, 1074–1090 e1074 (2021).
pubmed: 33862013 doi: 10.1016/j.str.2021.03.017
Schmidt, P. Small-angle scattering studies of disordered, porous and fractal systems. J. Appl. Crystallogr. 24, 414–435 (1991).
doi: 10.1107/S0021889891003400
Hurd, A. J., Schaefer, D. W. & Martin, J. E. Surface and mass fractals in vapor-phase aggregates. Phys. Rev. A Gen. Phys. 35, 2361–2364 (1987).
pubmed: 9898422 doi: 10.1103/PhysRevA.35.2361
Sharma, G. et al. Escherichia coli biofilm: development and therapeutic strategies. J. Appl. Microbiol. 121, 309–319 (2016).
pubmed: 26811181 doi: 10.1111/jam.13078
Ferenci, T. et al. Genomic sequencing reveals regulatory mutations and recombinational events in the widely used MC4100 lineage of Escherichia coli K-12. J. Bacteriol. 191, 4025–4029 (2009).
pubmed: 19376874 pmcid: 2698400 doi: 10.1128/JB.00118-09
Saldana, Z. et al. Synergistic role of curli and cellulose in cell adherence and biofilm formation of attaching and effacing Escherichia coli and identification of Fis as a negative regulator of curli. Environ. Microbiol. 11, 992–1006 (2009).
pubmed: 19187284 pmcid: 2672964 doi: 10.1111/j.1462-2920.2008.01824.x
Baba, T. et al. Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol. Syst. Biol. 2, 2006 0008 (2006).
Barnhart, M. M. & Chapman, M. R. Curli biogenesis and function. Annu. Rev. Microbiol. 60, 131–147 (2006).
pubmed: 16704339 pmcid: 2838481 doi: 10.1146/annurev.micro.60.080805.142106
Wu, H. et al. Activation of colanic acid biosynthesis linked to heterologous expression of the polyhydroxybutyrate pathway in Escherichia coli. Int. J. Biol. Macromol. 128, 752–760 (2019).
pubmed: 30726748 doi: 10.1016/j.ijbiomac.2019.02.004
Okshevsky, M. & Meyer, R. L. The role of extracellular DNA in the establishment, maintenance and perpetuation of bacterial biofilms. Crit. Rev. Microbiol. 41, 341–352 (2015).
pubmed: 24303798 doi: 10.3109/1040841X.2013.841639
Gish, W. & States, D. J. Identification of protein coding regions by database similarity search. Nat. Genet. 3, 266–272 (1993).
pubmed: 8485583 doi: 10.1038/ng0393-266
Ta, B. T. T. et al. Identification, recombinant protein production, and functional analysis of a M60-like metallopeptidase, secreted by the liver fluke Opisthorchis viverrini. Parasitol. Int. 75, 102050 (2020).
pubmed: 31901435 doi: 10.1016/j.parint.2019.102050
Hidalgo, G. et al. Functional tomographic fluorescence imaging of pH microenvironments in microbial biofilms by use of silica nanoparticle sensors. Appl. Environ. Microbiol. 75, 7426–7435 (2009).
pubmed: 19801466 pmcid: 2786433 doi: 10.1128/AEM.01220-09
Van Gerven, N., Van der Verren, S. E., Reiter, D. M. & Remaut, H. The role of functional amyloids in bacterial virulence. J. Mol. Biol. 430, 3657–3684 (2018).
pubmed: 30009771 pmcid: 6173799 doi: 10.1016/j.jmb.2018.07.010
Shanmugam, N. et al. Microbial functional amyloids serve diverse purposes for structure, adhesion and defence. Biophys. Rev. 11, 287–302 (2019).
pubmed: 31049855 pmcid: 6557962 doi: 10.1007/s12551-019-00526-1
Dueholm, M. S. et al. Functional amyloid in Pseudomonas. Mol. Microbiol 77, 1009–1020 (2010).
pubmed: 20572935
Evans, M. L. & Chapman, M. R. Curli biogenesis: order out of disorder. Biochim Biophys. Acta 1843, 1551–1558 (2014).
pubmed: 24080089 doi: 10.1016/j.bbamcr.2013.09.010
Pfefferkorn, C. M., McGlinchey, R. P. & Lee, J. C. Effects of pH on aggregation kinetics of the repeat domain of a functional amyloid, Pmel17. Proc. Natl Acad. Sci. USA 107, 21447–21452 (2010).
pubmed: 21106765 pmcid: 3003087 doi: 10.1073/pnas.1006424107
Morel, B., Varela, L., Azuaga, A. I. & Conejero-Lara, F. Environmental conditions affect the kinetics of nucleation of amyloid fibrils and determine their morphology. Biophys. J. 99, 3801–3810 (2010).
pubmed: 21112305 pmcid: 2998616 doi: 10.1016/j.bpj.2010.10.039
Zandomeneghi, G., Krebs, M. R., McCammon, M. G. & Fandrich, M. FTIR reveals structural differences between native beta-sheet proteins and amyloid fibrils. Protein Sci. 13, 3314–3321 (2004).
pubmed: 15537750 pmcid: 2287307 doi: 10.1110/ps.041024904
Groenning, M. et al. Study on the binding of Thioflavin T to beta-sheet-rich and non-beta-sheet cavities. J. Struct. Biol. 158, 358–369 (2007).
pubmed: 17289401 doi: 10.1016/j.jsb.2006.12.010
Serra, D. O., Richter, A. M. & Hengge, R. Cellulose as an architectural element in spatially structured Escherichia coli biofilms. J. Bacteriol. 195, 5540–5554 (2013).
pubmed: 24097954 pmcid: 3889604 doi: 10.1128/JB.00946-13
Qadri, F., Svennerholm, A. M., Faruque, A. S. & Sack, R. B. Enterotoxigenic Escherichia coli in developing countries: epidemiology, microbiology, clinical features, treatment, and prevention. Clin. Microbiol. Rev. 18, 465–483 (2005).
pubmed: 16020685 pmcid: 1195967 doi: 10.1128/CMR.18.3.465-483.2005
Chen, H. D. & Frankel, G. Enteropathogenic Escherichia coli: unravelling pathogenesis. FEMS Microbiol. Rev. 29, 83–98 (2005).
pubmed: 15652977 doi: 10.1016/j.femsre.2004.07.002
Fallingborg, J. Intraluminal pH of the human gastrointestinal tract. Dan. Med Bull. 46, 183–196 (1999).
pubmed: 10421978
Xu, Y. et al. An acid-tolerance response system protecting exponentially growing Escherichia coli. Nat. Commun. 11, 1496 (2020).
pubmed: 32198415 pmcid: 7083825 doi: 10.1038/s41467-020-15350-5
Lin, J. et al. Mechanisms of acid resistance in enterohemorrhagic Escherichia coli. Appl. Environ. Microbiol 62, 3094–3100 (1996).
pubmed: 8795195 pmcid: 168100 doi: 10.1128/aem.62.9.3094-3100.1996
Datsenko, K. A. & Wanner, B. L. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc. Natl Acad. Sci. USA 97, 6640–6645 (2000).
pubmed: 10829079 pmcid: 18686 doi: 10.1073/pnas.120163297
Cowieson, N. P. et al. Beamline B21: high-throughput small-angle X-ray scattering at diamond light source. J. Synchrotron Radiat. 27, 1438–1446 (2020).
pubmed: 32876621 pmcid: 7467336 doi: 10.1107/S1600577520009960
Franke, D. et al. ATSAS 2.8: a comprehensive data analysis suite for small-angle scattering from macromolecular solutions. J. Appl Crystallogr 50, 1212–1225 (2017).
pubmed: 28808438 pmcid: 5541357 doi: 10.1107/S1600576717007786
Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166 (2018).
Rohou, A. & Grigorieff, N. CTFFIND4: fast and accurate defocus estimation from electron micrographs. J. Struct. Biol. 192, 216–221 (2015).
pubmed: 26278980 pmcid: 6760662 doi: 10.1016/j.jsb.2015.08.008
Kelley, L. A., Mezulis, S., Yates, C. M., Wass, M. N. & Sternberg, M. J. The Phyre2 web portal for protein modeling, prediction and analysis. Nat. Protoc. 10, 845–858 (2015).
pubmed: 25950237 pmcid: 5298202 doi: 10.1038/nprot.2015.053
Pettersen, E. F. et al. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).
pubmed: 15264254 doi: 10.1002/jcc.20084
Delaglio, F. et al. NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J. Biomol. NMR 6, 277–293 (1995).
pubmed: 8520220 doi: 10.1007/BF00197809
Vranken, W. F. et al. The CCPN data model for NMR spectroscopy: development of a software pipeline. Proteins 59, 687–696 (2005).
pubmed: 15815974 doi: 10.1002/prot.20449
Johnson, B. A. & Blevins, R. A. NMR view: a computer program for the visualization and analysis of NMR data. J. Biomol. NMR 4, 603–614 (1994).
pubmed: 22911360 doi: 10.1007/BF00404272
Eng, J. K., McCormack, A. L. & Yates, J. R. An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database. J. Am. Soc. Mass Spectrom. 5, 976–989 (1994).
pubmed: 24226387 doi: 10.1016/1044-0305(94)80016-2
Micsonai, A. et al. BeStSel: a web server for accurate protein secondary structure prediction and fold recognition from the circular dichroism spectra. Nucleic Acids Res. 46, W315–W322 (2018).
pubmed: 29893907 pmcid: 6031044 doi: 10.1093/nar/gky497
Jaumot, J., Gargallo, R., de Juan, A. & Tauler, R. A graphical user-friendly interface for MCR-ALS: a new tool for multivariate curve resolution in MATLAB. Chemometrics Intell. Lab. Syst. 76, 101–110 (2005).
doi: 10.1016/j.chemolab.2004.12.007
Bro, R., De & Jong, S. A fast non-negativity-constrained least squares algorithm. J. Chemometrics 11, 393–401 (1997).
doi: 10.1002/(SICI)1099-128X(199709/10)11:5<393::AID-CEM483>3.0.CO;2-L
Schlafer, S. & Dige, I. Ratiometric imaging of extracellular pH in dental biofilms. J. Vis. Exp. 109, e53622 (2016).
Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).
pubmed: 22743772 doi: 10.1038/nmeth.2019
Florea, M. et al. Engineering control of bacterial cellulose production using a genetic toolkit and a new cellulose-producing strain. Proc. Natl Acad. Sci. USA 113, E3431–E3440 (2016).
pubmed: 27247386 pmcid: 4914174 doi: 10.1073/pnas.1522985113

Auteurs

Paula M Corsini (PM)

Centre for Host-Microbiome Interactions, Faculty of Dental, Oral & Craniofacial Sciences, King's College London, London, UK.
School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK.

Sunjun Wang (S)

Centre for Host-Microbiome Interactions, Faculty of Dental, Oral & Craniofacial Sciences, King's College London, London, UK.

Saima Rehman (S)

Centre for Host-Microbiome Interactions, Faculty of Dental, Oral & Craniofacial Sciences, King's College London, London, UK.

Katherine Fenn (K)

School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK.

Amin Sagar (A)

Centre de Biologie Structurale, Université de Montpellier, INSERM, CNRS, Montpellier, France.

Slobodan Sirovica (S)

Centre for Oral Bioengineering, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Leanne Cleaver (L)

Centre for Host-Microbiome Interactions, Faculty of Dental, Oral & Craniofacial Sciences, King's College London, London, UK.

Charlotte J C Edwards-Gayle (CJC)

Diamond Light Source Ltd., Diamond House, Harwell Science and Innovation Campus, Didcot, Oxfordshire, UK.

Giulia Mastroianni (G)

School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK.

Ben Dorgan (B)

Centre for Host-Microbiome Interactions, Faculty of Dental, Oral & Craniofacial Sciences, King's College London, London, UK.

Lee M Sewell (LM)

Centre for Host-Microbiome Interactions, Faculty of Dental, Oral & Craniofacial Sciences, King's College London, London, UK.

Steven Lynham (S)

Proteomics Facility, Centre of Excellence for Mass Spectrometry, King's College London, London, UK.

Dinu Iuga (D)

Department of Physics, University of Warwick, Coventry, UK.

W Trent Franks (WT)

Department of Physics, University of Warwick, Coventry, UK.

James Jarvis (J)

Randall Division of Cell and Molecular Biophysics and Centre for Biomolecular Spectroscopy, King's College London, London, UK.

Guy H Carpenter (GH)

Centre for Host-Microbiome Interactions, Faculty of Dental, Oral & Craniofacial Sciences, King's College London, London, UK.

Michael A Curtis (MA)

Centre for Host-Microbiome Interactions, Faculty of Dental, Oral & Craniofacial Sciences, King's College London, London, UK.

Pau Bernadó (P)

Centre de Biologie Structurale, Université de Montpellier, INSERM, CNRS, Montpellier, France.

Vidya C Darbari (VC)

School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK. v.darbari@qmul.ac.uk.

James A Garnett (JA)

Centre for Host-Microbiome Interactions, Faculty of Dental, Oral & Craniofacial Sciences, King's College London, London, UK. james.garnett@kcl.ac.uk.
School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK. james.garnett@kcl.ac.uk.

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