Type IV Secretion in Gram-Negative and Gram-Positive Bacteria

364 Pages·2017·9.086 MB·English

by  Steffen Backert, Elisabeth Grohmann

Current Topics in Microbiology and Immunology
Steffen Backert
Elisabeth Grohmann E ditors
Type IV Secretion
in Gram-Negative
and Gram-Positive
Bacteria
Current Topics in Microbiology
and Immunology
Volume 413
Series editors
RafiAhmed
SchoolofMedicine,RollinsResearchCenter,EmoryUniversity,RoomG211,1510CliftonRoad,
Atlanta,GA30322,USA
KlausAktories
MedizinischeFakultät,InstitutfürExperimentelleundKlinischePharmakologieundToxikologie,
Abt.I,Albert-Ludwigs-UniversitätFreiburg,Albertstr.25,79104,Freiburg,Germany
ArturoCasadevall
W.HarryFeinstoneDepartmentofMolecularMicrobiology&Immunology,JohnsHopkins
BloombergSchoolofPublicHealth,615N.WolfeStreet,RoomE5132,Baltimore,MD21205,
USA
RichardW.Compans
DepartmentofMicrobiologyandImmunology,EmoryUniversity,1518CliftonRoad,CNR5005,
Atlanta,GA30322,USA
JorgeE.Galan
BoyerCtr.forMolecularMedicine,SchoolofMedicine,YaleUniversity,295CongressAvenue,
room343,NewHaven,CT06536-0812,USA
AdolfoGarcia-Sastre
IcahnSchoolofMedicineatMountSinai,DepartmentofMicrobiology,1468MadisonAve.,
Box1124,NewYork,NY10029,USA
AkikoIwasaki
DepartmentofImmunobiology,TACS655,YaleUniversitySchoolofMedicine,POBOX
208011,NewHaven,CT06520-8011,USA
BernardMalissen
Centred’ImmunologiedeMarseille-Luminy,ParcScientifiquedeLuminy,Case906,13288,
MarseilleCedex9,France
KlausPalme
InstituteofBiologyII/MolecularPlantPhysiology,Albert-Ludwigs-UniversitätFreiburg,
Freiburg,79104,Germany
RinoRappuoli
GSKVaccines,ViaFiorentina1,Siena,53100,Italy
Honorary editors
MichaelB.A.Oldstone
DepartmentofImmunologyandMicrobiology,TheScrippsResearchInstitute,10550North
TorreyPinesRoad,LaJolla, CA92037,USA
PeterK.Vogt
DepartmentofMolecularandExperimentalMedicine,TheScrippsResearchInstitute,10550
NorthTorreyPinesRoad,BCC-239,LaJolla,CA92037,USA
More information about this series at http://www.springer.com/series/82
Steffen Backert Elisabeth Grohmann
(cid:129)
Editors
Type IV Secretion
in Gram-Negative
and Gram-Positive Bacteria
Responsible series editor: Klaus Aktories
123
Editors
SteffenBackert Elisabeth Grohmann
Division of Microbiology, Division of Microbiology,
Departmentof Biology Faculty ofLife Sciences
Friedrich Alexander University andTechnology
Erlangen-Nuremberg BeuthUniversity of Applied
Erlangen SciencesBerlin
Germany Berlin
Germany
ISSN 0070-217X ISSN 2196-9965 (electronic)
CurrentTopics inMicrobiology andImmunology
ISBN978-3-319-75240-2 ISBN978-3-319-75241-9 (eBook)
https://doi.org/10.1007/978-3-319-75241-9
LibraryofCongressControlNumber:2018930379
©SpringerInternationalPublishingAG,partofSpringerNature2017,correctedpublication2018
Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpart
of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations,
recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission
orinformationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilar
methodologynowknownorhereafterdeveloped.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexemptfrom
therelevantprotectivelawsandregulationsandthereforefreeforgeneraluse.
The publisher, the authors and the editors are safe to assume that the advice and information in this
book are believed to be true and accurate at the date of publication. Neither the publisher nor the
authorsortheeditorsgiveawarranty,expressorimplied,withrespecttothematerialcontainedhereinor
for any errors or omissions that may have been made. The publisher remains neutral with regard to
jurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations.
Printedonacid-freepaper
ThisSpringerimprintispublishedbytheregisteredcompanySpringerInternationalPublishingAG
partofSpringerNature
Theregisteredcompanyaddressis:Gewerbestrasse11,6330Cham,Switzerland
Foreword
T4SS—Then and Now
IwashonoredtobeaskedbySteffenBackertandElisabethGrohmanntoprovidea
Foreword for the book “Type IV Secretion in Gram-Negative and Gram-Positive
Bacteria,” which they have edited. After having worked in the field of plasmid
conjugation for decades, I was excited by the chapter list and impressed with the
large group of international experts they had assembled together to contribute. In
fact, writing the Foreword provided to me a wonderful excuse to read the entire
volume.
WhenIwasayounggraduatestudent,Iwasfascinatedbyreadingthepioneering
papersofAchtman,Willetts,andClark(1971,1972),whoreportedthefirstgenetic
analysis of the F-plasmid transfer region. I was in awe of the complexity of the
transfer operon that encoded nine genes and was estimated to be over 30 kb long.
Over 20 years later, the complete sequence of the F-plasmid transfer region
revealedthepresenceof15genesforF-typepilusassemblyaloneandanother9for
DNAtransfer,matingpairstabilization,andsurfaceandentryexclusion(Frostetal.
1994). The 70 amino acid pilin molecule resulted from the removal of a 52 amino
acidleaderpeptideandwasacetylatedatitsN-terminus.Atthisstage,wewondered
whyitwassocomplicated?Inthesameyear,thegroupofErichLankareportedthe
complete sequence of a generic IncP plasmid (Pansegrau et al. 1994). In addition,
P-type pilus assembly was shown to require 11 genes plus a peptidase that circu-
larizes theP-type pilinafter cleavage attwo sites, amost unusual molecule indeed
(Kalkumetal.2004).Asidefromunusualpilinproteins,otherdifferencesincluded
anextraATPaseintheP-typesystemsandthepresenceofsixextragenesinF-type
systems, some which contain high numbers of conserved cysteine residues (TraN
has 22), involved in mating pair stabilization and pilus retraction (Arutyunov and
Frost 2013), two traits not seen in P-type systems.
At about the same time, the Ti plasmid T-DNA, which is responsible for
tumorigenesis in plants, was found to specify a P-type pilus and pilus assembly
apparatus capable of delivering the T-DNA into a plant cell. This proved to be a
v
vi Foreword
more tractable system for studying DNA transfer, and rapid progress was made in
understandingthatthe11geneproductsdefinedatypeIVsecretionsystem(T4SS),
which were duly named VirB1-11 (Christie 1997; Kado 2014). These names are
nowuseduniversallyforthecoreT4SSgeneproducts,althoughtheymightnotbe
directlyassociatedwithavirulencephenotypeineachcase.MostT4SSgeneshave
namesthatarespecifictoaparticularsystemaswellasdesignationasVirBorVirD
proteins. A movement is afoot to have VirB1-11 called TivB1-11 to designate
membershipintheT4SSfamilyratherthanuse“Vir”attheriskofbeingconfusing
(Thomas et al. 2017).
In the early days of conjugative plasmid research, the focus was on F and the
related R factors within the IncF complex (Incompatibility group F) and the IncI
plasmids (Meynell et al. 1968). This early work, using simple reagents and
pilus-specific antibodies, showed that the IncF and IncI plasmids specified very
different pilus types. Coupled with the work of David Bradley on pilus-specific
phages (reviewed in Frost 1993) for a large number of Inc groups, it became clear
thatthere weretwopilustypes that definedflexible(F)andrigid(I,P)pilustypes.
This work was prescient in that it defined what we now know as the type IVA
(T4ASS, F and P-like) and type IVB (T4BSS, I-like) systems (reviewed in
Chapter “Biological Diversity and Evolution of Type IV Secretion Systems,”
Christie,ValeroandBuchrieser).Thehomologybetween theVirandIncPtransfer
regions isstriking, whereasthe homology toF transfer systems ismore difficult to
detect,withlowidentityvalues.Initially,thereappearedtobethreetypesofT4SSs,
F, P, and I. However, large-scale sequencing projects revealed many chimeric
transfersystemsthathadanF-typeT4SS,butexpressedacircularP-typepilin(e.g.,
theIncHI1plasmidR27,Sherburneetal.2000).Thesearequitecommonlyfound,
especiallyinclinicalisolates,suggestingthatF-andP-typeT4SSsaremoresimilar
thantheyaredifferent.Consequently,theyarenowconsideredsubtypesofthesame
group.
Another landmark paper that used thin sectioning of a single layer of mating
cells reported on the close contact between the donor and recipient cells over an
extensive area of both their surfaces (Dürrenberger et al. 1991). Although the
resolutionwasverygood,therewasnoevidenceforamatingapparatusorbridgein
theseimages,suggestingthatthematingporeiseitherverysmallorveryscarceor
forms transiently in response to an unknown signal. The hunt for this mating pore
has been a long-sought goal, and researchers in the T4SS field felt somewhat
enviousofthosestudyingtypeIIIsecretionsystems,forinstance,whoseneedle-like
structures, related to flagellar basal bodies, could be purified intact (Diepold and
Armitage 2015). With the development of high-resolution cryo-electron micro-
scopy in the last ten years, the structures of a putative T4SS and the F-type pilus
have been determined (see Chapter “Structural and Molecular Biology of Type IV
SecretionSystems,”Bergé,WaksmanandTerradot).TheprototypeT4SSisarather
large structure,approximately185Åby340Å,anditisamarvel tomethat ithas
neverbeenseeninthecellenvelopenorhasitbeenpurifiedintactfromcells.There
is something transient and ephemeral about the T4SS. It is as if the pilus is a
primitivetouchsystemandthatthereisasignalrelayedfromthetipofthepilusto
Foreword vii
its base that results in formation of the complete structure, allowing it to transport
bothproteinandnucleicacid.Thewholequestionoftheenvironmentalandgenetic
signalsthatgoverntheexpression,assembly,andfunctionoftheT4SSisdiscussed
in Chapter “Prokaryotic Information Games: How and When to Take Up and
Secrete DNA” (Stingl and Koraimann).
AlongunansweredquestionhasbeenwhethertheDNAcouldpassthroughthe
lumenofthepilus,about20Åindiameter,andwhetherproteinscouldpassthrough
it as well. There have been many hints that large complexes can be transported,
such as the passage of the RNA-A protein complex of RNA phages during phage
eclipseandpenetration(Krahnetal.1972)andtheconjugativetransportofprimase
proteins in IncP and IncI systems (Merryweather et al. 1986; Rees and Wilkins
1989), tonametwo.Thefinding thatVirproteinsweretransferredtotheplantcell
duringtumorigenesisusinggenetictechniquessuchastheCRAFTassay(Vergunst
etal.2000)confirmedwhathadbeenpreviouslyrumoredaboutT4SS.Thisunusual
anduniqueabilitytotransportproteinandnucleicacid(eitherRNAorDNAinboth
directions, during phage infection, conjugation, or transformation) has provided a
target for inhibiting this process as reviewed by Baron and Sharifahmadian
(Chapter “Type IV Secretion in Agrobacterium Tumefaciens and Development of
Specific Inhibitors”).
Conjugation requires an energized membrane, a mating bridge between donor
andrecipientcellspresumablyformedbytheT4SS,andtheproteinsresponsiblefor
initiating and processing DNA transfer. These latter proteins, in complex with the
DNA substrate, form the relaxosome (Chapter “Relaxases and Plasmid transfer in
Gram-NegativeBacteria,”ZechneranddelaCruz).Thiscomplexcontains,inmost
cases, two ATPases, a relaxase and a coupling protein. Whereas the relaxase is
importantforsingle-strandedDNAtransfer,thecouplingprotein,VirD4,isthereal
hallmarkofaconjugativesystem.Theessentialroleofthecouplingproteinsinboth
ssDNAanddsDNAtransferisreviewedinChapter“CouplingProteinsinTypeIV
Secretion” (Llosa and Alkorta).
Conjugative transfer in Gram-positive (Gram+) bacteria has long been noted in
severalspeciesandhasbeenstudiedindetailinEnterococcusfaecalis(Dunnyand
Berntsson2016).ThepresenceinGram+bacteriaofamodifiedT4SS,inwhichtwo
ofthesignatureATPases(VirB4andVirD4,thecouplingprotein)andaVirB1-like
transglycosylase can easily be discerned, by insilicoanalysis, hasreally expanded
our knowledge about the versatility of T4SS. No pilus appears to be required for
conjugative DNA transfer in Gram+ species; instead, the T4SS is adapted to their
single membrane and robust cell wall that must be breached in both the donor and
recipient. Other Gram+ bacteria such as Streptomyces and certain archaea use a
coupling protein similar to the partitioning protein FtsK or sporulation protein
SpoIIIE that can transfer double-stranded DNA without a T4SS. That plasmid
transfer could be whittled down to a single Tra protein and a few inessential
accessory proteins was a revelation at the time (Kendall and Cohen 1988). The
findings with Gram+ bacteria certainly call into question the role of the pilus.
A more detailed discussion of progress in Gram+ conjugation is reviewed in
viii Foreword
Grohmann, Keller, and Muth (Chapter “Mechanisms of Conjugative Transfer and
Type IV Secretion-Mediated Effector Transport in Gram-Positive Bacteria”).
Sequencing of bacterial genomes has revealed the presence of T4SS in many
−
pathogenic Gram-negative (Gram ) bacteria, on plasmids, and within the chro-
mosome on pathogenicity islands (PAIs) and integrative conjugative elements
(ICEs).IfT4SSscansecreteproteinsduringconjugation,thenanobviousquestion
is whether they can transport effector molecules into a host target cell or the
subcellular spaces such as vacuoles during the infectious process. Our under-
standing of the cagT4SS of Helicobacter pylori has increased greatly in the 22
years since its complete sequence was reported (Backert et al., Chapter “The
Helicobacter pylori Type IV Secretion System Encoded by the Cag Pathogenicity
Island:Architecture,FunctionandSignaling”).T4ASSsarealsoresponsibleforthe
pathogenicity of Bartonella and Brucella species (Chapter “Type IV Effector
Secretion and Subversion of Host Functions by Bartonella and Brucella Species,”
Dehio and Tsolis) and the tick-borne Rickettsiales members Anaplasma phagocy-
tophyllum and Ehrlichia chaffeensis (Chapter “Role and Function of the Type IV
Secretion System in Anaplasma and Ehrlichia Species,” Rikihisa). Similarly, the
T4BSS, characterized as the icm/dot locus of Legionella pneumophila, has been
extensively studied in a few pathogens. This T4SS is responsible for the
intravacuolar lifestyle of Legionella (Chapter “Subversion of Host Membrane
Dynamics by the Legionella Dot/Icm Type IV Secretion System,” Roy, Hilbi and
Nagai) as well as delivery of a vast array of effectors and metaeffectors during
infection by Coxiella burnetii (Chapter “Beginning to Understand the Role of the
Type IV Secretion System Effector Proteins in Coxiella burnetii Pathogenesis,”
Lührmann, Newton and Bonazzi).
AbacteriumthatI’vekeptaneyeonformanyyearsisNeisseriagonorrhoeae.It
was known to encode a type II secretion system (T2SS) that assembles a type IV
pilus,asubjectofstudyformyPh.D.thesis,longbeforeaT4SSwasdiscoveredin
its genome sequence. That it uses this T4SS to extrude single-stranded DNA into
the media to facilitate transformation and gene conversion, a key factor in
Neisseria’s modus vivendi, is truly unique (Chapter “Secretion of Chromosomal
DNAbytheNeisseriaGonorrhoeaeTypeIVSecretionSystem,”Callaghanetal.).
Thistakesusfullcirclebacktomyyouthwhenwewouldponderwhetherwecould
“trick” plasmids into releasing DNA into the medium.
TheprogressintheT4SSfield(indeed,secretioningeneral)overthelast10–20
years has been really remarkable (Grohmann et al. 2018). However, there are still
many aspects of T4SSs that are puzzling. How does the system know that a
recipient or host cell has been found? Is this the sole function of the pilus or is it
involvedinmacromoleculartransport?Ifitis,thenwhydoGram+bacterianothave
piliandindeed,whyareP-typepilishedfromthecellintothemedium?Howdoes
−
the nucleic acid or protein getinto thetarget recipient cell? In Gram conjugation,
the DNA appears to bypass the periplasm and is transported into the cytoplasm
directly.Isthereatubethatextendsthroughthetwocellenvelopessimilartothetail
tubes of phages? Would this also be true for the delivery of effector proteins in
pathogens? Is it possible to see the T4BSS structure in the cell? Why is there an
Foreword ix
extra ATPase (VirB11) in P-type systems and what is it doing? There are still so
many questions!
I am very pleased to see so much progress on these systems. I look forward to
new findings in T4SS and congratulate the contributors to this book on their
remarkable advancement so far. May it continue.
Edmonton, AB, Canada Laura S. Frost
Professor Emerita
Department of Biological Sciences
University of Alberta
References
AchtmanM,Willetts N,ClarkAJ(1971)Beginning ageneticanalysisofconjugationaltransfer
determined by the F factor in Escherichia coli by isolation and characterization of
transfer-deficientmutants.JBacteriol106(2):529–538
Achtman M, Willetts N, Clark AJ (1972) Conjugational complementation analysis of
transfer-deficientmutantsofFlacinEscherichiacoli.JBacteriol110(3):831–842
ArutyunovD,FrostLS(2013)Fplasmidconjugation:backtothebeginning.Plasmid70(1):18–32
Christie PJ (1997) Agrobacterium tumefaciens T-complex transport apparatus: a paradigm for a
newfamilyofmultifunctionaltransportersineubacteria.JBacteriol179(10):3085–3094
Diepold A, Armitage JP (2015) Type III secretion systems: the bacterial flagellum and the
injectisome.PhilTransRSocLondBBiolSci370(1679):20150020
Dunny GM, Berntsson RP-A (2016) Enterococcal sex pheromones: evolutionary pathways to
complex,two-signalsystems.JBacteriol198(11):1556–1562
Dürrenberger MB, Villiger W, Bächi T (1991) Conjugational junctions: morphology of specific
contactsinconjugatingEscherichiacolibacteria.JStructuralBiol107(2):146–156
Frost LS (1993) Conjugative pili and pilus-specific phages. In: Clewell D (ed) Conjugation,
PlenumPress,NewYork,p189–221
FrostLS,Ippen-IhlerK,SkurrayRA(1994)Ananalysisofthesequenceandgeneproductsofthe
transferregionoftheFsexfactor.MicrobiolRev58:162–210
GrohmannE,ChristiePJ,WaksmanG,BackertS(2018)TypeIVsecretioninGram-negativeand
Gram-positivebacteria.MolMicrobiolhttps://doi.org/10.1111/mmi.13896
KadoCI(2014)Historicaleventsthatspawnedthefieldofplasmidbiology.MicrobiolSpectr2(5).
https://doi.org/10.1128/microbiolspec.PLAS-0019-2013
KalkumM,EisenbrandtR,LankaE(2004)Proteincircletsassexpilussubunits.CurrProteinPept
Sci5(5):417–424
KendallKJ,CohenSN(1988)CompletenucleotidesequenceoftheStreptomyceslividansplasmid
pIJ101andcorrelationofthesequencewithgeneticproperties.JBacteriol170(10):4634–4651
KrahnPM,O’CallaghanRJ,ParanchychW(1972)StagesinphageR17infection:VI.injectionof
aproteinandRNAintothehostcell.Virol47(3):628–637
MerryweatherA,ReesCE,SmithNM,WilkinsBM(1986)Roleofsogpolypeptidesspecifiedby
plasmidColIb-P9andtheirtransferbetweenconjugatingbacteria.EMBOJ5(11):3007–3012
Meynell E, Datta N, Lawn AM, Meynell GG (1968) Ancestral relationships of transmissible
bacterialplasmids.JGenMicrobiol50(3):Suppl-v
Pansegrau W, LankaE,Barth PT, Figurski DH, Guiney DG, Haas D,Helinski DR, Schwab H,
StanisichVA,ThomasCM(1994)CompletenucleotidesequenceofBirminghamIncPalpha
plasmids.Compilationandcomparativeanalysis.JMolBiol239(5):623–663
Rees CE, Wilkins BM (1989) Transfer of Tra proteins into the recipient cell during bacterial
conjugationmediatedbyplasmidColIb-P9.JBacteriol171(6):3152–3157