Basic Medical Microbiology

Book Preface

What is the bigger challenge—for a student or the instructor to understand what is important in medical microbiology? Many years ago when I took my irst graduate course in medical microbiology, I read thousands of pages of text, listened to 5 hours of lectures a week, and performed lab exercises 6 hours a week for 1 year. I was given a wonderful foundation in microbiology, but I frequently asked the question—that was voiced by all the students—do I really need to know all this stuf? he answer to that question is certainly no, but the challenge is what information is needed. Years later when I set out to write my irst textbook on microbiology, my goal was to only give the students what they need to know, described in a way that is informative, factual, and concise. I think I was successful in that efort, but I also realize that the discipline of microbiology continues to change as do approaches to presenting information to the students. I am still irmly convinced that my eforts in my irst textbook, Medical Microbiology, and subsequent editions are important, forming the foundation of microbiology knowledge for a student. his cannot be replaced by a quick search of the internet or a published review because much of the subject matter presented in Medical Microbiology— epidemiology, virulence, clinical diseases, diagnostics, treatment—is a distillation of the review of numerous research articles and clinical and technical experience. Having stated that, students frequently turn to review books consisting of abbreviated summaries, illustrations (should I say cartoons), and various mnemonic aids for mastering this subject. As I have watched this evolution of learning microbiology, I am struck by the sacriice that has been made. I believe microbiology is a beautiful subject, with the balance between health and disease deined by the biology of individual organisms and microbial communities. Without an understanding of the biology, lists of facts are soon forgotten. But I am a realist and know the burden students face, mastering not only microbiology but also a number of other subjects. So the personal question I posed was—is there a better way to present to the student a summary of information that is easy to understand and remember? his book is my approach to solving this question. First, almost by deinition, it is not comprehensive. Just as I have carefully selected organisms and diseases to present in this book, I have also intentionally not mentioned others—not because they are unimportant but
because they are less common. I have also not presented a detailed discussion of microbial biology and virulence or the immune response of the patient to an infection, but simply presented the association between an organism and disease. Again, I felt those discussions should be reserved for Medical Microbiology. Finally, the organization of this book is focused on organisms—bacteria,
viruses, fungi, and parasites—rather than diseases. I do this because I think it is easier for a student to remember a limited number of diseases associated with an organism rather than a long list of organisms (or a signiicantly incomplete list) implicated in a speciic disease such as pneumonia. Still, patients present with disease and the observer must develop a list of organisms that could be responsible; so to aid the student, I provide this diferential diagnosis in the introductory chapter of each organism section (Chapters 2, 12, 18, and 22). I also provide in these introductory chapters an overview of the classiication of the organisms (a structural framework for remembering the organisms) and a listing of antimicrobials that are used to treat infections. he individual chapters in Sections 1–4 are organized in a common theme: brief discussion of the individual organisms, a summary of facts (properties, epidemiology, clinical disease, diagnosis, treatment) provided in a concise table, illustrations provided as a visual learning aid, and clinical cases to reenforce the clinical signiicance of the organisms. Finally, examination questions are provided to help the student assess their ability to assimilate this material. Again, I will emphasize that this text should not be considered a comprehensive review of microbiology. On the other hand, I believe if the student masters this material, he or she will have a irm foundation in the principles and applications of microbiology. I certainly welcome all comments on how successful my eforts are.

I would like to acknowledge the support and guidance from the Elsevier professionals who help bring this concept to reality, particularly Jim Merritt, Katie DeFrancesco, Nicole DiCicco, and Tara Delaney. Additionally, I want to thank the many students who have challenged me to think about broad world of microbes and distill this into the essential material they must master, and my professional business colleagues who stimulated me to explain complex microbiology information in a factual but coherent story for a novice in this field.

Overview of Medical Microbiology

Microbiology can certainly be overwhelming for the student confronted with the daunting task of learning about hundreds of medically important microbes. I remember well the irst day in my introductory graduate course in medical microbiology; the course instructor handed each student a 1000-page syllabus consisting of lecture outlines, notes, and literature references. hat became known not so lovingly as the book of pain. However, microbiology is not so challenging if the subject matter—the microbes—are subdivided into groups and further subdivided into related units. Let me illustrate this in this introductory chapter.
Microbes are subdivided into one of four groups: • Viruses • Bacteria • Fungi • Parasites he structural complexity of these groups increases from viruses (the most simple structure) to parasites (the most complex). here is generally no confusion about which group a microbe should be placed in, although a few fungi were formerly classiied with the parasites. Each group of microbes is then further subdivided, generally based on a key feature of the group.

VIRUSES AND BACTERIA

Viruses Viruses are very simple microbes, consisting of nucleic acid, a few proteins, and (in some) a lipid envelope. hese microbes are completely dependent on the cells they infect for their survival and replication. Medically important viruses are subdivided into 20 families deined by the structural properties of the members. he most important feature is the nucleic acid. Viruses contain either DNA or RNA but not both. he families of DNA viruses and RNA viruses are further subdivided into viruses with either single-stranded or double-stranded nucleic acids. Lastly, these viral families are further subdivided into viruses with an outer envelope, or naked nonenveloped viruses. Now the perceptive student would say that this gives us 8 families of viruses and not 20. Well, the viruses are further subdivided by their shape (spherical or rodlike) and size (big or small [“pico”]). hus the key to understanding viruses is to place them into their respective families based on their structural features.

Bacteria Bacteria are a bit more complex, with both RNA and DNA, metabolic machinery for self-replication, and a complex cell wall structure. Bacteria are prokaryotic organisms; that is, simple unicellular organisms with no nuclear membrane, mitochondria, Golgi bodies, or endoplasmic reticulum and they reproduce by asexual division. he key feature that is used to separate most
bacteria is their staining property, with the Gram stain and acid-fast stain the most important. Most bacteria are either gram-positive (retain the blue dye) or gram-negative (lose the blue stain and stain with the red dye). hese bacteria are then subdivided by their shape (either spherical [cocci] or rod-shaped), whether they grow aerobically or anaerobically (many bacteria grow in both atmospheres and are called facultative anaerobes), and whether they form resilient spores or not (only gram-positive rods are sporeformers). he other important bacterial stain is the acid-fast stain that is retained only by a few bacteria that have a characteristic lipid-rich cell wall. his group is further subdivided by how diicult it is to remove the acid-fast stain (the stain is named because an acid solution removes the stain from most other bacteria). Finally, there are groups of organisms that do not stain with these procedures so they are separated by other features, such as shape (spiral-shaped bacteria) or their need to grow inside a host cell (e.g., leukocyte) or cell cultures in the laboratory.

FUNGI AND PARASITES
Fungi and parasites are more complex eukaryotic organisms that contain a well-deined nucleus, mitochondria, Golgi bodies, and endoplasmic reticulum. Single-celled and multi-celled organisms are members of both groups. As can be seen, the line separating these two groups is not as well deined as that separating these organisms from the bacteria or viruses, but the classiication is still well recognized.

Fungi Fungi are subdivided into single-celled organisms (yeasts) or multi-celled organisms (molds), with a few medically important members existing in both forms (dimorphic fungi). Molds are complex organisms with the cells organized into threadlike tubular structures (hyphae) and specialized asexual reproductive forms (conidia). he molds are then further subdivided by the structure of the hyphae (pigmented or nonpigmented, separated into individual cells [septated molds] or not) and the arrangement of the conidia.
Parasites Parasites are also subdivided into single-celled organisms (protozoa) or multi-celled organisms (worms and bugs). Members of the family Protozoa are then further divided into amebae, lagellates (think of them as hairy protozoa), and coccidia (some are spherical – shaped but many are not). he worms (technically called helminthes) are nicely classiied by their shape: roundworms, latworms, and tapeworms. Pretty simple, although many have very complex lifecycles that unfortunately are important for understanding how they cause disease. he bugs are simply “bugs.” hese include mosquitos, ticks, leas, lice, mites, and lies. hey are important because they are vectors of a number of viruses and bacteria (not fungi) that are responsible for diseases. Other bugs obviously exist (such as spiders), but these generally are not vectors for other pathogenic microbes.

GOOD VERSUS BAD MICROBES
Microbes, particularly the bacteria, have unjustly earned a bad reputation. Most are viewed as bad and recognized only for their ability to cause diseases. We have coined the derogatory term germs, and great eforts are made to eliminate our exposure to these organisms. he reality is most microbes are not only good but critical for our health. he surfaces of the skin, nose, mouth, gut, and genitourinary tract are covered with bacteria, as well as some fungi and parasites. hese organisms are critical for the maturation
of our immune system, important metabolic functions such as the digestion of food products, and protection from infection with unwanted pathogens. hese organisms are referred to as our normal lora or microbiome. If these organisms are maintained in their proper balance, then health can be maintained. If they are disrupted either naturally or through manmade interventions (e.g., antibiotics, skin peels, enemas) then we risk disease. Infectious diseases are also initiated when the members of the microbiome are introduced into normally sterile sites (e.g., abdominal cavity, tissues, lungs, urinary tract) through trauma or disease. his is referred to as an endogenous infection or an infection caused by the normal microbial population. Finally, infections can be caused by exogenous organisms; that is, those introduced from outside. Only a few of the microbes that we encounter from our environment are pathogens, but some of the most serious infections are caused by these exogenous pathogens. So the important lesson is that most microbes are good and not associated with disease.
A subset of our endogenous organisms can cause disease when introduced into normally sterile areas, but most endogenous organisms do not have the virulent properties to cause disease. Likewise, most of the exogenous organisms we are exposed to cause no problems at all, but some can cause quite signiicant disease. It is important to understand which organisms have the necessary properties (virulence) to cause disease and under what circumstances this will occur. It is also important to understand which organisms to ignore because they are not associated with disease.

CONCLUSION
The perceived complexity of microbiology is simpliied if we understand the relationships between members of each of the four groups of microbes. his is further simpliied if we separate the pathogens from nonpathogens and then understand the conditions under which the pathogens produce disease. he following chapters are designed to develop these themes for the individual groups of organisms.