**Meet the editor**

Dr. Bruna Maria Roesler is a pharmacist biochemist and holds a Master's Degree in Pharmacology and a Doctoral Degree in Basic Sciences – Internal Medicine from State University of Campinas (Campinas, SP, Brazil), where she has identified the principal genotypes of Helicobacter pylori in patients with chronic gastritis, peptic ulcer disease and early and advanced gastric adenocarci-

noma through molecular biology techniques. She has published her work in several peer-reviewed journals and given oral and poster presentations at various congresses. She is a member of the Helicobacter pylori Research Group Study from State University of Campinas, including the study of etiology, epidemiology and physiopathology of gastrointestinal diseases. She has also participated in research that reports the possible relationship between H. pylori infection and idiopathic thrombocytopenic purpura, as well as between H. pylori infection and liver diseases. Her postdoctoral work includes the study of H. pylori in extradigestive manifestations, especially regarding pancreas and perigastric lymphonodes from patients with gastric adenocarcinoma.

Contents

**Preface IX**

Marshall

**Section 1 Immunopathology and Genetic Diversity 1**

Chapter 2 **Immune Response to Helicobacter pylori 79**

**Section 2 Questions Concerning Possible Routes of H. pylori**

Chapter 3 **Can Drinking Water Serve as a Potential Reservoir of**

**Section 3 H. pylori and Gastric Cancer: Molecular Epidemiology and**

Chapter 4 **Molecular Epidemiology of Helicobacter pylori in Brazilian**

Bruna Maria Roesler and José Murilo Robilotta Zeitune

**Eradication Enough to Prevent Gastric Cancer 155**

**Epigenetic Diversity 3**

Batool Mutar Mahdi

**Transmission: Water 97**

**Helicobacter pylori 99**

**Possibilities of Prevention 121**

**the Prognosis of the Disease 123**

Chapter 5 **Helicobacter pylori Infection and Gastric Cancer — Is**

Chapter 1 **Persistence of Helicobacter pylori Infection: Genetic and**

Mohammed Benghezal, Jonathan C. Gauntlett, Aleksandra W. Debowski, Alma Fulurija, Hans-Olof Nilsson and Barry James

**Helicobacter pylori? Evidence for Water Contamination by**

**Patients with Early Gastric Cancer and a Review to Understand**

Aleksandra Sokic-Milutinovic, Dragan Popovic, Tamara Alempijevic, Sanja Dragasevic, Snezana Lukic and Aleksandra Pavlovic-Markovic

Malgorzata Plonka, Aneta Targosz and Tomasz Brzozowski

## Contents

### **Preface XIII**


Chapter 13 **The Mechanisms of Action and Resistance to Fluoroquinolone**

Contents **VII**

**in Helicobacter pylori Infection 349** Carolina Negrei and Daniel Boda


Chapter 12 **Empirical Versus Targeted Treatment of Helicobacter pylori Infections in Southern Poland According to the Results of Local Antimicrobial Resistance Monitoring 321** Elżbieta Karczewska, Karolina Klesiewicz, Paweł Nowak, Edward Sito, Iwona Skiba, Małgorzata Zwolińska–Wcisło, Tomasz Mach and Alicja Budak

#### Chapter 13 **The Mechanisms of Action and Resistance to Fluoroquinolone in Helicobacter pylori Infection 349** Carolina Negrei and Daniel Boda

**Section 4 H. pylori Infection in Children and Possible Causes of Iron**

Chapter 7 **Helicobacter pylori Infection, Gastric Physiology and**

**Section 5 Modern Methods of Bacterial DNA Recovering 225**

Chapter 8 **Helicobacter pylori and Liver – Detection of Bacteria in Liver**

Chapter 9 **Helicobacter pylori Infection — Challenges of Antimicrobial**

Amidou Samie, Nicoline F. Tanih and Roland N. Ndip

Chapter 10 **Helicobacter pylori — Current Therapy and Future Therapeutic**

Chapter 11 **Floating Drug Delivery Systems for Eradication of Helicobacter pylori in Treatment of Peptic Ulcer Disease 303** Yousef Javadzadeh and Sanaz Hamedeyazdan

Chapter 12 **Empirical Versus Targeted Treatment of Helicobacter pylori**

**Antimicrobial Resistance Monitoring 321**

Rajinikanth Siddalingam and Kumarappan Chidambaram

Chapter 6 **Particulars of the Helicobacter pylori Infection in Children 177**

**Micronutrient deficiency (Iron and Vitamin C) in Children in**

**Tissue from Patients with Hepatocellular Carcinoma Using Laser Capture Microdissection Technique (LCM) 227**

Elizabeth Maria Afonso Rabelo-Gonçalves, Bruna Maria Röesler and

**Chemotherapy and Emergence of Alternative Treatments 243**

**Infections in Southern Poland According to the Results of Local**

Elżbieta Karczewska, Karolina Klesiewicz, Paweł Nowak, Edward Sito, Iwona Skiba, Małgorzata Zwolińska–Wcisło, Tomasz Mach and

**Deficiency Anemia 175**

**Developing Countries 205**

José Murilo Robilotta Zeitune

**Strategies 241**

**Strategies 279**

Alicja Budak

**Section 6 Eradication Therapy of H. pylori Infection: New**

Shafiqul Alam Sarker

Florica Nicolescu

**VI** Contents

Preface

among others.

breakthroughs in medical care.

borne infection remains possible.

The first successful isolation of *Helicobacter pylori* by Warren and Marshall has brought a new era in gastric microbiology. Although spiral microorganisms had been observed in the gastric mucus layer many years before, the isolation of *H. pylori* in conjunction with in‐ creased interest in the pathogenesis of gastrointestinal diseases, as well as the relatively fre‐ quent availability of clinical specimens via endoscopic biopsy, has led to important

*H. pylori* remains one of the most common worldwide human infections and, although its colonization is not a disease in itself, it is a condition that affects the relative risk of develop‐ ing various clinical disorders of the upper gastrointestinal tract, such as chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT lymphoma) and gastric ad‐ enocarcinoma. Besides, in the last two decades, *H. pylori* infection has been associated with the development of some extradigestive diseases, such as hepatobiliary, cardiovascular and pancreatic diseases, iron deficiency anemia and idiopathic thrombocytopenic purpura,

Even though the routes of transmission of *H. pylori* are not completely clarified, infection is usually acquired during childhood and is characterized as being chronic, with greater prev‐ alence in developing countries in all ages. Person-to-person transmission and intrafamilial spread seem to be the main route, based on the intrafamilial clustering. Children are often infected by a strain with a genetic fingerprint identical to that of their parents, and they maintain this genotype even after moving to a different environment. Besides, the water‐

All individuals with *H. pylori* infection have histological gastritis, which corresponds to clas‐ sical chronic gastritis and is characterized by the infiltration of neutrophils and other inflam‐ matory cells. However, most patients are asymptomatic for life, while only some will come to develop a digestive disease. Nevertheless, gastric cancer is a disease that continues to be a major global health problem and still remains the leading cause of cancer-related deaths in many parts of the world. Gastric cancer development involves the interaction of three major factors, the agent (in the most part of the cases, H. pylori) and its pathogenicity, the charac‐ teristics of the host, and the external environment. Specifically regarding *H. pylori* infection, there are some studies indicating that the eradication of the microorganism could reduce the incidence of gastric cancer in patients without precancerous lesions or, when lesions are present, the eradication may or may not reduce this incidence. Also, when the eradication is done after endoscopic mucosal resection in patients with early gastric adenocarcinoma, it

could decrease the recurrence of metachronous gastric cancer in some patients.

## Preface

The first successful isolation of *Helicobacter pylori* by Warren and Marshall has brought a new era in gastric microbiology. Although spiral microorganisms had been observed in the gastric mucus layer many years before, the isolation of *H. pylori* in conjunction with in‐ creased interest in the pathogenesis of gastrointestinal diseases, as well as the relatively fre‐ quent availability of clinical specimens via endoscopic biopsy, has led to important breakthroughs in medical care.

*H. pylori* remains one of the most common worldwide human infections and, although its colonization is not a disease in itself, it is a condition that affects the relative risk of develop‐ ing various clinical disorders of the upper gastrointestinal tract, such as chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT lymphoma) and gastric ad‐ enocarcinoma. Besides, in the last two decades, *H. pylori* infection has been associated with the development of some extradigestive diseases, such as hepatobiliary, cardiovascular and pancreatic diseases, iron deficiency anemia and idiopathic thrombocytopenic purpura, among others.

Even though the routes of transmission of *H. pylori* are not completely clarified, infection is usually acquired during childhood and is characterized as being chronic, with greater prev‐ alence in developing countries in all ages. Person-to-person transmission and intrafamilial spread seem to be the main route, based on the intrafamilial clustering. Children are often infected by a strain with a genetic fingerprint identical to that of their parents, and they maintain this genotype even after moving to a different environment. Besides, the water‐ borne infection remains possible.

All individuals with *H. pylori* infection have histological gastritis, which corresponds to clas‐ sical chronic gastritis and is characterized by the infiltration of neutrophils and other inflam‐ matory cells. However, most patients are asymptomatic for life, while only some will come to develop a digestive disease. Nevertheless, gastric cancer is a disease that continues to be a major global health problem and still remains the leading cause of cancer-related deaths in many parts of the world. Gastric cancer development involves the interaction of three major factors, the agent (in the most part of the cases, H. pylori) and its pathogenicity, the charac‐ teristics of the host, and the external environment. Specifically regarding *H. pylori* infection, there are some studies indicating that the eradication of the microorganism could reduce the incidence of gastric cancer in patients without precancerous lesions or, when lesions are present, the eradication may or may not reduce this incidence. Also, when the eradication is done after endoscopic mucosal resection in patients with early gastric adenocarcinoma, it could decrease the recurrence of metachronous gastric cancer in some patients.

Various guidelines for the management of *H. pylori* infection worldwide are available. Gen‐ erally, the eradication of *H. pylori* in adults is recommended when the bacterium is present in the gastric mucosa. However, a discussion may arise about whether or not to recommend specific treatment in asymptomatic individuals that receive positive diagnoses for *H. pylori* in routine exams. In these cases, patients should be advised about the therapy, the adverse effects resulting from the use of the chosen medications, and the importance of *H. pylori* eradication in order to prevent some gastric diseases, such as peptic ulcer disease and gas‐ tric cancer. Nowadays, not only several drugs and regimens are in use, but also phytothera‐ py compounds have been associated with healing properties attributed, for instance, to the inhibition of cytokine-mediated inflammatory mechanism and to antioxidant activities. Be‐ sides, new systems of drug delivery systems have been developed and new regimens have been studied, considering the antimicrobial resistance.

Dr. Nicolescu describes the particulars of *H. pylori* infection in children, and summarizes im‐ portant aspects of this infection, such as the rate of *H. pylori* infection, prevalence, possibility of transmission, principal diagnostic methods, incriminatory factors, pathophysiology and dissemination, among others, concluding the main text considering prospects studies.

Preface XI

Dr. Sarker presents a chapter concerning *H. pylori* infection, gastric physiology and iron defi‐ ciency anemia in children in developing countries. The main text brings aspects of hyper‐ chlorhydria and hypochlorhydria and the role of *H. pylori* in gastric acid perturbation in children. After this, the chapter explains the possible relationship between *H. pylori* infection

Dr. Rabelo-Gonçalves and colleagues present a research study describing the detection of *H. pylori* in liver tissue samples through laser capture microdissection technique (LCM), consid‐ ering that this method can be extensively applied for bacterium identification in samples

Dr. Samie and colleagues describe the challenge of antimicrobial chemotherapy and the emergence of alternative treatments that have been used to eradicate *H. pylori* infection. Geographic differences in predominant *H. pylori* genotypes are delineated and the principal treatment regimens are discussed. Resistance mechanisms to metronidazole, clarithomycin, amoxicillin, tetracycline and fluoroquinolone are depicted. Potential treatments with medici‐ nal plants are described, considering the principal plants used in Africa, Europe, South and North America, Asia and Australia. In addition, honey and probiotics are described as pos‐

Dr. Rajinikanth presents the current and future therapeutic strategies that can be used to eradicate *H. pylori* infection. First-line, second-line and third-line therapies are described as well as future therapeutic strategies, including novel drug delivery approaches, among them the floating drug delivery systems (FDDS) and the mucoadhesive drug delivery sys‐ tems (MDDS). In addition, the development of vaccine against *H. pylori* and genome-based

Dr. Javadzadeh and Dr. Hamedeyazdan present a chapter that discusses the importance of drug delivery systems in treatment of upper gastrointestinal diseases, especially peptic ulcer disease. The floating drug delivery systems are explained as well as the principal therapies

Dr. Karczewska and colleagues describe a research concerning the empirical and the target‐ ed treatment of *H. pylori* infection in Southern Poland according to the results of local anti‐ microbial resistance monitoring. The principal characteristics and virulence factors of *H. pylori* are explained as well as the treatment guidelines commonly used to eradicate its infec‐ tion. Antimicrobial resistance in Poland is described and the results obtained suggest the need for constant monitoring of the resistance to a set of antimicrobial agents routinely used

Finally, Dr. Negrei and colleagues describe the mechanisms of action and resistance to fluo‐ roquinolone in *H. pylori* infection, including the interaction with bacterial DNA gyrase and topoisomerase IV, the SOS gene network response and the plasmid mediated resistance, among other resistance mechanisms. In addition, the clinical and social implications of fluo‐

sible sources in the treatment and management of *H. pylori* infection.

and iron deficiency anemia.

with small quantities of DNA.

drug discovery are also depicted.

for empirical therapy.

roquinolone resistance are depicted.

that are currently used to *H. pylori* eradication.

All these aspects are considered in this book which is divided into following sections: Im‐ munopathology and genetic diversity; Questions concerning possible routes of *H. pylori* transmission: water; *H. pylori* and gastric cancer: molecular epidemiology and possibilities of prevention; *H. pylori* infection in children and possible causes of iron deficiency anemia; Modern methods of bacterial DNA recovering; and Eradication therapy of *H. pylori* infec‐ tion: new strategies.

Dr. Benghezal and colleagues present an interesting chapter regarding *H. pylori* genetic and epigenetic plasticity, discussing the hypothesis that this plasticity promotes *H. pylori* adapta‐ tion to individual human hosts by generating phenotypically diverse populations. A mathe‐ matical modeling of *H. pylori* chronic infection, its micro-evolution and related mechanisms for the generation of diversity including genetic and epigenetic diversity is also described. Finally, the chapter summarizes important alternatives to antibiotic treatment by targeting *H. pylori* persistence based on the urease enzymes.

Dr. Mahdi describes the important mechanisms of host immune response to *H. pylori* infec‐ tion, which can be divided into innate and adaptive response, also describing the evasion of bacterium to the immune response. Besides, some aspects of vaccination against *H. pylori* infection are also considered.

Dr. Plonka and colleagues present a chapter that highlights the principal possible routes of *H. pylori* transmission, especially the evidence for water contamination. The principal sour‐ ces and pathways of transmission are described as well as the methods used for the detec‐ tion of bacterium in waterborne.

Dr. Roesler and Dr. Zeitune present a chapter that can be divided into two sections: the mo‐ lecular characterization of *H. pylori* strains in Brazilian patients with early gastric adenocar‐ cinoma through molecular techniques, specifically polymerase chain reaction, and the discussion of the principal aspects of *H. pylori* infection and the development of precancer‐ ous lesions and early gastric cancer properly, trying to highlight to what extent the microor‐ ganism eradication treatment could be important to preventing the disease progression.

Dr. Sokic-Milutinovic and colleagues describe the principal virulence factors of *H. pylori* that have been associated to gastric cancer development, considering that the outcome of the in‐ fection also depends on characteristics of the host and environmental factors. They also dis‐ cussed these important aspects and considered them to suggest if *H. pylori* eradication is enough to prevent gastric cancer development.

Dr. Nicolescu describes the particulars of *H. pylori* infection in children, and summarizes im‐ portant aspects of this infection, such as the rate of *H. pylori* infection, prevalence, possibility of transmission, principal diagnostic methods, incriminatory factors, pathophysiology and dissemination, among others, concluding the main text considering prospects studies.

Various guidelines for the management of *H. pylori* infection worldwide are available. Gen‐ erally, the eradication of *H. pylori* in adults is recommended when the bacterium is present in the gastric mucosa. However, a discussion may arise about whether or not to recommend specific treatment in asymptomatic individuals that receive positive diagnoses for *H. pylori* in routine exams. In these cases, patients should be advised about the therapy, the adverse effects resulting from the use of the chosen medications, and the importance of *H. pylori* eradication in order to prevent some gastric diseases, such as peptic ulcer disease and gas‐ tric cancer. Nowadays, not only several drugs and regimens are in use, but also phytothera‐ py compounds have been associated with healing properties attributed, for instance, to the inhibition of cytokine-mediated inflammatory mechanism and to antioxidant activities. Be‐ sides, new systems of drug delivery systems have been developed and new regimens have

All these aspects are considered in this book which is divided into following sections: Im‐ munopathology and genetic diversity; Questions concerning possible routes of *H. pylori* transmission: water; *H. pylori* and gastric cancer: molecular epidemiology and possibilities of prevention; *H. pylori* infection in children and possible causes of iron deficiency anemia; Modern methods of bacterial DNA recovering; and Eradication therapy of *H. pylori* infec‐

Dr. Benghezal and colleagues present an interesting chapter regarding *H. pylori* genetic and epigenetic plasticity, discussing the hypothesis that this plasticity promotes *H. pylori* adapta‐ tion to individual human hosts by generating phenotypically diverse populations. A mathe‐ matical modeling of *H. pylori* chronic infection, its micro-evolution and related mechanisms for the generation of diversity including genetic and epigenetic diversity is also described. Finally, the chapter summarizes important alternatives to antibiotic treatment by targeting

Dr. Mahdi describes the important mechanisms of host immune response to *H. pylori* infec‐ tion, which can be divided into innate and adaptive response, also describing the evasion of bacterium to the immune response. Besides, some aspects of vaccination against *H. pylori*

Dr. Plonka and colleagues present a chapter that highlights the principal possible routes of *H. pylori* transmission, especially the evidence for water contamination. The principal sour‐ ces and pathways of transmission are described as well as the methods used for the detec‐

Dr. Roesler and Dr. Zeitune present a chapter that can be divided into two sections: the mo‐ lecular characterization of *H. pylori* strains in Brazilian patients with early gastric adenocar‐ cinoma through molecular techniques, specifically polymerase chain reaction, and the discussion of the principal aspects of *H. pylori* infection and the development of precancer‐ ous lesions and early gastric cancer properly, trying to highlight to what extent the microor‐ ganism eradication treatment could be important to preventing the disease progression.

Dr. Sokic-Milutinovic and colleagues describe the principal virulence factors of *H. pylori* that have been associated to gastric cancer development, considering that the outcome of the in‐ fection also depends on characteristics of the host and environmental factors. They also dis‐ cussed these important aspects and considered them to suggest if *H. pylori* eradication is

been studied, considering the antimicrobial resistance.

*H. pylori* persistence based on the urease enzymes.

enough to prevent gastric cancer development.

tion: new strategies.

X Preface

infection are also considered.

tion of bacterium in waterborne.

Dr. Sarker presents a chapter concerning *H. pylori* infection, gastric physiology and iron defi‐ ciency anemia in children in developing countries. The main text brings aspects of hyper‐ chlorhydria and hypochlorhydria and the role of *H. pylori* in gastric acid perturbation in children. After this, the chapter explains the possible relationship between *H. pylori* infection and iron deficiency anemia.

Dr. Rabelo-Gonçalves and colleagues present a research study describing the detection of *H. pylori* in liver tissue samples through laser capture microdissection technique (LCM), consid‐ ering that this method can be extensively applied for bacterium identification in samples with small quantities of DNA.

Dr. Samie and colleagues describe the challenge of antimicrobial chemotherapy and the emergence of alternative treatments that have been used to eradicate *H. pylori* infection. Geographic differences in predominant *H. pylori* genotypes are delineated and the principal treatment regimens are discussed. Resistance mechanisms to metronidazole, clarithomycin, amoxicillin, tetracycline and fluoroquinolone are depicted. Potential treatments with medici‐ nal plants are described, considering the principal plants used in Africa, Europe, South and North America, Asia and Australia. In addition, honey and probiotics are described as pos‐ sible sources in the treatment and management of *H. pylori* infection.

Dr. Rajinikanth presents the current and future therapeutic strategies that can be used to eradicate *H. pylori* infection. First-line, second-line and third-line therapies are described as well as future therapeutic strategies, including novel drug delivery approaches, among them the floating drug delivery systems (FDDS) and the mucoadhesive drug delivery sys‐ tems (MDDS). In addition, the development of vaccine against *H. pylori* and genome-based drug discovery are also depicted.

Dr. Javadzadeh and Dr. Hamedeyazdan present a chapter that discusses the importance of drug delivery systems in treatment of upper gastrointestinal diseases, especially peptic ulcer disease. The floating drug delivery systems are explained as well as the principal therapies that are currently used to *H. pylori* eradication.

Dr. Karczewska and colleagues describe a research concerning the empirical and the target‐ ed treatment of *H. pylori* infection in Southern Poland according to the results of local anti‐ microbial resistance monitoring. The principal characteristics and virulence factors of *H. pylori* are explained as well as the treatment guidelines commonly used to eradicate its infec‐ tion. Antimicrobial resistance in Poland is described and the results obtained suggest the need for constant monitoring of the resistance to a set of antimicrobial agents routinely used for empirical therapy.

Finally, Dr. Negrei and colleagues describe the mechanisms of action and resistance to fluo‐ roquinolone in *H. pylori* infection, including the interaction with bacterial DNA gyrase and topoisomerase IV, the SOS gene network response and the plasmid mediated resistance, among other resistance mechanisms. In addition, the clinical and social implications of fluo‐ roquinolone resistance are depicted.

"Trends in Helicobacter pylori Infection" will certainly provide an updated set of informa‐ tion in all the principal aspects of *H. pylori* infection, enriching the knowledge of the whole scientific community.

The editor expresses her thankfulness for the excellent work of the contributing authors. The editor thanks Ms. Danijela Duric, head of production at InTech, for her invitation to edit this book. In addition, the editor is especially thankful for the excellent support given by Ms. Iva Lipovic, as well as the entire InTech Open Access publishing team.

#### **Dr. Bruna Maria Roesler**

**Section 1**

**Immunopathology and Genetic Diversity**

Pharmacist Biochemist Department of Internal Medicine, Center of Diagnosis of Digestive Diseases, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil **Immunopathology and Genetic Diversity**

"Trends in Helicobacter pylori Infection" will certainly provide an updated set of informa‐ tion in all the principal aspects of *H. pylori* infection, enriching the knowledge of the whole

The editor expresses her thankfulness for the excellent work of the contributing authors. The editor thanks Ms. Danijela Duric, head of production at InTech, for her invitation to edit this book. In addition, the editor is especially thankful for the excellent support given by Ms. Iva

Department of Internal Medicine, Center of Diagnosis of Digestive Diseases,

Faculty of Medical Sciences, State University of Campinas,

**Dr. Bruna Maria Roesler** Pharmacist Biochemist

Campinas, São Paulo, Brazil

Lipovic, as well as the entire InTech Open Access publishing team.

scientific community.

XII Preface

**Chapter 1**

**Persistence of** *Helicobacter pylori* **Infection: Genetic and**

*Helicobacter pylori* is a Gram negative bacterium found on the luminal surface of the gastric epithelium. Infection is generally acquired during childhood and persists life-long in the absence of antibiotic treatment. *H. pylori* has a long period of co-evolution with humans, going back at least since human migration out of Africa about 60, 000 years ago [1, 2]. This coevolution is reflected in DNA sequence signatures observed in *H. pylori* strains of different geographic origin and has enabled the mapping of human migration out of Africa. This prolonged and intimate relationship is likely to have shaped the large and diverse repertoire of strategies which *H. pylori* employs to establish robust colonization and persist in the gastric niche. Key challenges that *H. pylori* encounters are fluctuation of acidic pH of the gastric lumen, peristalsis of the mucus layer leading to washout in the lower intestine, nutrient scarcity, and the innate and adaptive immune responses promoting local inflammation or gastritis [3-8]. These challenges, particularly host immune responses, are likely to represent the selective pressure driving *H. pylori* micro-evolution during transmission leading to persistence in the

Host defences against *H. pylori* have been extensively studied including mechanisms which *H. pylori* uses to avoid or inhibit an effective host immune response and review of these related studies is beyond the scope of this chapter (see reviews [9-24]). Instead, key strategies of *H. pylori* immune escape with emphasis on regulation of inflammation are succinctly presented in the context of *H. pylori* persistence. *H. pylori* has evolved to avoid detection by pattern recognition receptors of the innate immune system, such as toll-like receptors and C-type

> © 2014 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**Epigenetic Diversity**

http://dx.doi.org/10.5772/57428

**1. Introduction**

human host.

Mohammed Benghezal, Jonathan C. Gauntlett,

Aleksandra W. Debowski, Alma Fulurija,

Hans-Olof Nilsson and Barry James Marshall

Additional information is available at the end of the chapter
