Table Of ContentSteff en Backert · Yoshio Yamaoka
Editors
Helicobacter
pylori
Research
From Bench to Bedside
Helicobacter pylori Research
ThiSisaFMBlankPage
Steffen Backert • Yoshio Yamaoka
Editors
Helicobacter pylori Research
From Bench to Bedside
Editors
SteffenBackert YoshioYamaoka
DivisionofMicrobiology FacultyofMedicine
DepartmentofBiology DepartmentofEnvironmentaland
FriedrichAlexanderUniversity PreventiveMedicine
Erlangen-Nuremberg OitaUniversity
Erlangen,Germany Yufu,Japan
DepartmentofMedicine-Gastroenteology
BaylorCollegeofMedicine
Houston,USA
ISBN978-4-431-55934-4 ISBN978-4-431-55936-8 (eBook)
DOI10.1007/978-4-431-55936-8
LibraryofCongressControlNumber:2016935851
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Foreword
Helicobacter pylori, the Gastric Bacterium Which Still
Infects Half the World’s Population, Is an Important
Part of Gastroenterology and Infectious Disease
It is exciting to participate in this new “state-of-the-art” book about Helicobacter
pylori, the gastric bacterium which still infects half of the human race and which
promises to challenge clinicians and scientists for decades to come. The book is
structuredsoastoplaceH.pyloriinperspectiveasthegastricbacteriumattached
itself to prehistoric humans and followed their migrations, through the stone-age
intothetwenty-firstcentury.Thusthefirstchapter,byYoshanMoodley,setsusup
to ask the questions which can then be answered in depth by the other experts.
WheredidH.pyloricomefrom?Howdoesitsurviveinthestomach?Whatunique
adaptations have taken place, which allow it to persist throughout life? If it
colonised mankind for so long, was there once a useful purpose in having
H.pylori?Isitstillusefulinsomeway?Ascompletegenomesequencingtechnol-
ogybecomeswidespread,manywillusethisin-depthinitialchapterasahypothesis
generatingknowledge-baseforourownmolecularepidemiologystudies.Examples
areevengivenofnewertechnologiessuchasRNAseq,forexamininggeneexpres-
sion and intergenic control regions. Later, Ichizo Kobayashi predicts that further
breakthroughs via OMICS analyses will also provide more insight into the evolu-
tionofboththegenomeandmethylomeofthishighlydiversemodelorganism.
Once the big picture has been described, we want to know how H. pylori
accomplishesthisand“what makes ittick?” So we delveinto H.pylori biochem-
istryrealisingthatthemetabolismofthebugmirrorsthemicroenvironmentofthe
gastric mucosa (Fischer and deReuse, Praszkier, Sutton and Ferrero; Backert,
Zanotti, Lind, Asche and Tegtmeyer; Cover, Holland and Blanke; Arnqvist;
Wessler; Pernitzsch, Darfeuille and Sharma). In a hostile acidic milieu, but under
themucuslayer,H.pylorisolvetheproblemsofimmediatesurvivalbutthenmust
deal with the host’s attempts to remove the invader. Certainly, its very plastic
v
vi Foreword
genomeisanadvantagecoupledwiththemassivenumbersoforganismscompeting
for life in that niche. But other mechanisms exist whereby H. pylori regulate the
immuneresponse,optimisingitsnutritionwithoutallowingthemucosatobetotally
disrupted by too vigorous tissue reaction. Subtle degrees of positive and negative
feedbackmustbeatwork.Aclearexplanationoftheinterrelatedvirulencefactors,
primarilyCagAandVacA,andthentheseveralnewersurfaceantigensisgivenin
subsequent chapters, perhaps explaining how H. pylori disguises itself from the
immuneresponse.
As we move from basic to clinical research in H. pylori, animal models of the
infection become even more important. Chapters on this theme describe the
100-year-longhistoryofvariousrelatedHelicobactersinanimalsandmorerecent
insights into their genomics and taxonomy (Flahon, Haesebrouck and Smet;
Solnick, Eaton and Peek; Mu¨ller and Hartung; Oshima, Nakayama and Oshima;
McLean; Nicoll, Saw, Hold and El-Omar). How the animal infections provide
guidanceintotherealmofanimalmodelsremainsimportant.Chaptersonthetrials
andtribulationsofcurrentanimalmodelsservetoemphasisethattheperfectanimal
modelisyettobediscovered,unlessitisstillthehuman.Nevertheless,selectionof
or direct manipulation of small animal genetics serves to tease out important
predictorsofepidemiology,colonisation,inflammationandcarcinogenesis.
In this context, the clinician will be delighted to study the detailed clinical
chapters on human diseases related to H. pylori infection (Boltin and Niv; Genta
andLash;WroblewskiandPeek;Sagaert;KoletzkoandMegraud).Thereasonsto
treat H. pylori and features of the host and the bacterium which drive the various
phenotypes of asymptomatic, ulcerated and malignant gastric disorders will give
confidence to the clinician seeing patients with gastric disorders. In addition, the
spectreofrarernon-gastricdisordersisexposed,asthesewillbeseenfromtimeto
time andthe gastroenterologistorinfectious disease specialistwill beexpectedto
assistdecisionsintotheirmanagementtoo.Veryrelevanthereisthecontroversial
area of immune modulation from H. pylori. It is relevant to many areas, but the
tantalising possibility exists that H. pylori could still play a useful role, as an
immunemodulator,like“oilontroubledwaters”todecreasetheapparentovershoot
which commonly occurs in allergy susceptible individuals. Certainly the negative
association with asthma in New York children and in adults with various inflam-
matorygastrointestinaldiseasesisworthyofstudyandisauthoritativelyreviewed
inimmunology-relatedandpaediatricchapters.
Finally, it is great to see that the common, real-world issues of H. pylori
treatmentaredealtwithbyauthorswhohavemanyyearsofexperiencesuccessfully
curing difficult to treat patients (Molina-Infante and Graham; Malfertheiner and
Selgrad; Torres, Correa, Herrero, Piazuelo and Ferrecio; Miftahussurur and
Yamaoka; Vale, Vitor and Oleastro; Raghavan and Quiding-Ja¨rbrink). While the
level of antibiotic resistance has been creeping up, most notably to macrolides
and quinolones, logical planning of treatment, with sophisticated microbiological
testing, can give us confidence. Several new antibiotics and/or combinations of
well-knowndrugsmeanthereisabright,H.pylori-freefutureforpatientswiththe
bacterium.
Foreword vii
Finally,weareshownglimpsesofthetwenty-firstcenturyfuturewhereH.pylori
infectionmightbeprevented,oreradicatedrathersimply,ineachcontinent.Thisis
already starting and will become easier as the knowledge in this book is dissemi-
nated. Strategies toimprove hygiene, vaccinate,treat and even suppress H.pylori
withfoodsandprobioticsupplementsareallrelevanthereandarenowbeingtested.
In summary then, every science graduate will enjoy the intelligent structure of
thisbookwhichusesin-depthexplanationofthecurrentknowledgetosuggesthow
gastric colonisation with H. pylori might be a tool tounlocksecrets related to the
physiologyofthegastrointestinaltractandthegastrointestinalimmunesystem.The
clinicianalsowillbedelightedwiththeextensivediscussionsofimportantdisease
associations and then, most importantly, how to render the patient H. pylori
negative.
TheHelicobacterResearchLaboratory BarryMarshall
TheMarshallCentreforInfectiousDiseases
ResearchandTraining,PaLMM504
PerthWA6009,Australia
2015
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Contents
PartI BacteriologyandMolecularBiology
1 Helicobacterpylori:Genetics,Recombination,Population
Structure,andHumanMigrations. . . . . . . . . . . . . . . . . . . . . . . . . 3
YoshanMoodley
2 AdaptationofHelicobacterpyloriMetabolismtoPersistent
GastricColonization. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Fre´de´ricFischerandHildeDeReuse
3 VirulenceMechanismsofHelicobacterpylori:AnOverview. . . . . . 57
JudytaPraszkier,PhilipSutton,andRichardL.Ferrero
4 RolesofthecagPAIandCagAonGastroduodenalDiseases. . . . . . 89
SteffenBackert,GiuseppeZanotti,JudithLind,CarmenIsabellAsche,
andNicoleTegtmeyer
5 HelicobacterpyloriVacuolatingToxin. . . . . . . . . . . . . . . . . . . . . . . 113
TimothyL.Cover,RobinL.Holland,andStevenR.Blanke
6 RolesoftheBabAandtheSabAAdhesinsinGastroduodenal
Diseases. . . .. . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . .. . . . . 143
AnnaArnqvist
7 EmergingNovelVirulenceFactorsofHelicobacterpylori. . . . . . . . 165
SiljaWessler
8 ThePrimaryTranscriptomeandNoncodingRNARepertoire
ofHelicobacterpylori. .. . . . .. . . .. . . . .. . . . .. . . . .. . . .. . . . .. 189
SandyR.Pernitzsch,FabienDarfeuille,andCynthiaM.Sharma
9 GenomeEvolution:HelicobacterpyloriasanExtremeModel. . . . . 217
IchizoKobayashi
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