Bacterial Pathogenesis

A Molecular Approach

Brenda A. Wilson, Malcolm Winkler, Brian T. Ho, Brenda A. Wilson, Malcolm Winkler

• Publisher: ASM Press
• Year: 2019
• Print ISBN: 9781555819408
• eBook ISBN: 9781683672883
• Edition: 4
• Topic: Medicine
• Subtopic: Medical Microbiology & Parasitology

This highly anticipated update of the acclaimed textbook draws on the latest research to give students the knowledge and tools to explore the mechanisms by which bacterial pathogens cause infections in humans and animals. Written in an approachable and engaging style, the book uses illustrative examples and thought-provoking exercises to inspire students with the potential excitement and fun of scientific discovery.

Completely revised and updated, and for the first time in stunning full-color, Bacterial Pathogenesis: A Molecular Approach, Fourth Edition, builds on the core principles and foundations of its predecessors while expanding into new concepts, key findings, and cutting-edge research, including new developments in the areas of the microbiome and CRISPR as well as the growing challenges of antimicrobial resistance. All-new detailed illustrations help students clearly understand important concepts and mechanisms of the complex interplay between bacterial pathogens and their hosts. Study questions at the end of each chapter challenge students to delve more deeply into the topics covered, and hone their skills in reading, interpreting, and analyzing data, as well as devising their own experiments. A detailed glossary defines and expands on key terms highlighted throughout the book. Written for advanced undergraduate, graduate, and professional students in microbiology, bacteriology, and pathogenesis, this text is a must-have for anyone looking for a greater understanding of virulence mechanisms across the breadth of bacterial pathogens.

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IN THIS CHAPTER

Why Are Bacteria So Much in the Public Health Spotlight Nowadays?

Bacteria, a Formidable Ancient Life Form

Pressing Current Infectious Disease Issues

Emerging and Reemerging Infectious Diseases

Foodborne and Waterborne Infections

Modern Medicine as a Source of New Diseases

Postsurgical and Other Wound Infections

Bioterrorism

A New Respect for Prevention

Surveillance: An Early Warning System

Making Hospitals Safe for Patients

And Now for Some Good News: You’ve Got a Bacterial Infection!

The Helicobacter pylori Revolution

The Aftermath

Microbiota Shift Diseases

A Brave New World of Pathogenesis Research

The New Age of Genomics

Insights into Pathogen Evolution

Modeling the Host-Pathogen Interaction in Experimental Animals

Correlation Studies

Selected Readings

Questions

CHAPTER 1

The Power of Bacteria

N ever underestimate a potential adversary that has had a 3-billion-year evolutionary head start.

Why Are Bacteria So Much in the Public Health Spotlight Nowadays?

Widespread clinical use of antibiotics first began in the 1950s. The availability of these “miracle drugs,” as they were called at the time, caused great excitement for both physicians and the public as a whole. They came at a time when the medical community was gaining greater control over infectious diseases than ever before. In clinics and hospitals, hygienic practices such as handwashing and disinfectant use were reducing the risk of disease transmission. In the community, improved nutrition made people better able to resist infections, while less crowded conditions and the availability of clean water helped reduce the spread of disease. Meanwhile, newly developed vaccines were protecting against some much-feared diseases. Despite all this, bacterial infections, such as pneumonia, tuberculosis, cholera, and syphilis, continued to take a heavy toll, and infectious diseases were still a leading cause of death. Antibiotics appeared to be the superweapon that would give humans the final decisive victory over bacteria.

In this early euphoria over the success of antibiotics, scientists and policy makers alike concluded that bacterial infections were no longer a threat and turned their attention to other problems, such as cancer, heart disease, and viral infections. For the next three decades, bacteria were of interest mainly as tractable model systems for studying physiology, genetics, and ecology, and as a source of tools for the new molecular biology and genetic engineering technologies that were revolutionizing all of biology. Confidence that bacterial diseases were completely under control was bolstered by a glut of new antibiotics on the market. Indeed, there was a pervasive perception among the medical community and the public as a whole that bacterial infectious diseases were no longer a problem since they could now be readily and effectively treated with antibiotics.

Unnoticed by all but a few researchers in the field and some pharmaceutical companies, the first cracks soon began to appear in the protective shield against bacterial diseases. This danger became more evident in the late 1970s. Antibiotics were no longer the highly profitable products they had once been, especially not compared to heart medications or tranquilizers, which needed to be taken daily for long periods of time. Additionally, new antibiotics were becoming harder to discover and more expensive to develop. One pharmaceutical company after another quietly cut back or dismantled its antibiotic discovery program. For a while, these cracks appeared not to matter, as there were enough new antibiotics that still worked on the bacteria that had become resistant to the old standbys like penicillin. Warnings from scientists that bacteria were becoming more resistant to antibiotics were largely ignored.

During the late 1980s, however, scientists and health officials began to notice an alarming increase in difficult-to-treat bacterial infections. By 1995, infectious diseases became one of the top five causes of death in the United States. Even with the AIDS epidemic in full swing, most infectious disease deaths were still caused by bacterial diseases, such as pneumonia and bacterial bloodstream infections (sepsis). Why was the incidence of bacterial pneumonia and sepsis increasing? For one, the population as a whole was aging, and older people are more susceptible to these diseases. For another, modern medicine had created a large and growing population of patients whose immune systems were temporarily disrupted due to cancer chemotherapy or immunosuppressive therapy following organ transplants, as well as due to other immune-compromising illnesses such as AIDS.

A development that caught many in the medical community by surprise was the appearance of new diseases that were dubbed emerging infectious diseases. In the past, scientists had assumed that any microorganism capable of causing disease would surely have done so by now, given the hundreds of thousands of years humans have occupied the planet. This view overlooked two important facts. First, bacteria can very rapidly change their genetic makeup to take advantage of new opportunities. Members of some bacterial populations are hypermutable, allowing them to try many genetic combinations to find the one most appropriate for the current environment experienced by that bacterium. Many bacteria can also acquire genes conferring new virulence traits or resistance to antibiotics from other related or even unrelated bacteria through a phenomenon known as horizontal gene transfer (HGT). Second, changing human practices, such as increased global travel, widespread use of air-conditioning, and the appearance of crowded intensive care wards in big hospitals, brought susceptible people into contact with microorganisms that had not previously had the opportunity to cause human infections.

A new category of disease-causing bacteria was recognized: opportunistic pathogens. These bacteria normally do not cause disease in healthy people, but can infect and cause disease in individuals whose defenses are compromised in some way. In fact, many of these pathogens are found normally in or on the human body and thus had been assumed to be innocuous. Others are bacteria commonly found in soil or aquatic environments. During the early antibiotic era, these soil bacteria were thought to be beneficial to humans because scientists were finding that many of them were producers of antibiotics. However, these bacteria were suddenly being seen as the only bacterium isolated from the blood, lungs, feces, or wounds of seriously ill patients. They also tend to exhibit a troubling, not-so-friendly characteristic. Because of the antibiotics present in their natural environment, they are often intrinsically resistant to a variety of antibiotics, which made infections by these opportunistic bacteria challenging to treat.

Scientists and physicians reluctantly began to realize that a decisive human victory over bacteria had not occurred. Not only were known pathogens changing to be more resistant to antibiotics or better able to cause disease, but also new pathogens with markedly different virulence traits were emerging. The infectious disease picture was changing in a way that made it increasingly difficult to predict new patterns of bacterial disease. The serious threat of antibiotic-resistant bacteria to human health both in the United States and the world was documented in 2013 by reports from the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO).

Bacteria, a Formidable Ancient Life Form

The brief foregoing account of how bacterial diseases have come into prominence as a major global health problem explored the recent past. However, to understand fully why no one should have been surprised by this development and why bacteria are such formidable opponents, it is necessary to take a closer look at the long history of bacteria, during which they were constantly forced to evolve and adapt to new conditions.

Today, we realize that Earth is a microbial planet. Bacteria were probably the first form of life to appear on Earth, about 3.5 to 4 billion years ago (Figure 1-1). Bacteria and another type of prokaryote, the archaea, ruled the world unchallenged for at least a billion years before the first eukaryotes appeared. During this period, they helped create the global geochemical cycles that made Earth habitable for larger life forms. Bacteria and archaea are master recyclers. Bacteria put the first molecular oxygen in Earth’s atmosphere, thereby creating the ozone layer, which protected Earth’s surface from the deadly radiation that had previously bombarded it, making life on Earth’s surface possible. By adding molecular oxygen to the atmosphere, bacteria created conditions that permitted the later evolution of oxygen-utilizing creatures, including humans.

Figure 1-1. Overview of microbial evolution. Microorganisms appeared 3.5 to 4 billion years ago and changed Earth such that eukar...

Table of contents

• Cover
• Title Page
• Copyright
• Dedication
• Contents
• Preface
• In Memoriam
• About the Authors
• Chapter 1: The Power of Bacteria
• Chapter 2: Skin and Mucosa: The First Lines of Defense against Bacterial Infections
• Chapter 3: The Innate Immune System: Always on Guard
• Chapter 4: The Adaptive Defenses: Antibodies and Cytotoxic T Cells
• Chapter 5: The Microbiota of the Human Body: Microbiomes and Beyond
• Chapter 6: Microbes and Disease: Establishing a Connection
• Chapter 7: Mechanisms of Genetic Modification and Exchange: Role in Pathogen Evolution
• Chapter 8: Identification of Virulence Factors: Measuring Infectivity and Virulence
• Chapter 9: Identification of Virulence Factors: Molecular Approaches for Bacterial Factors
• Chapter 10: Identification of Virulence Factors: Molecular Approaches for Host Factors
• Chapter 11: Bacterial Strategies for Colonization and Survival in the Host
• Chapter 12: Toxins and Other Toxic Virulence Factors
• Chapter 13: Delivery of Virulence Factors
• Chapter 14: Virulence Regulation
• Chapter 15: Antimicrobial Compounds and Their Targets
• Chapter 16: Antibiotic Resistance
• Chapter 17: Vaccination: A Critical Component of the Modern Medical Armamentarium
• Chapter 18: The Gram-Positive Opportunistic Pathogens
• Chapter 19: The Gram-Negative Opportunistic Pathogens
• Chapter 20: The Changing Roles of Microbiologists in an Age of Bioterrorism and Emerging Diseases
• Glossary
• Index