Chapter 1: Introduction to Medical Microbiology PDF

# Chapter 1: Introduction to Medical Microbiology Imagine the excitement felt by the Dutch biologist Anton van Leeuwenhoek in 1674 as he peered through his carefully ground microscopic lenses at a drop of water and discovered a world of millions of tiny "animalcules". Almost 100 years later, the D...

# Chapter 1: Introduction to Medical Microbiology Imagine the excitement felt by the Dutch biologist Anton van Leeuwenhoek in 1674 as he peered through his carefully ground microscopic lenses at a drop of water and discovered a world of millions of tiny "animalcules". Almost 100 years later, the Danish biologist Otto Müller extended van Leeuwenhoek's studies and organized bacteria into genera and species according to the classification methods of Carolus Linnaeus. This was the beginning of the taxonomic classification of microbes. In 1840, the German pathologist Friedrich Henle proposed criteria for proving that microorganisms were responsible for causing human disease (the "germ theory" of disease). Robert Koch and Louis Pasteur confirmed this theory in the 1870s and 1880s with a series of elegant experiments proving that microorganisms were responsible for causing anthrax, rabies, plague, cholera, and tuberculosis. Other brilliant scientists went on to prove that a diverse collection of microbes was responsible for causing human disease. The era of chemotherapy began in 1910, when the German chemist Paul Ehrlich discovered the first antibacterial agent, a compound effective against the spirochete that causes syphilis. This was followed by Alexander Fleming's discovery of penicillin in 1928, Gerhard Domagk's discovery of sulfanilamide in 1935, and Selman Waksman's discovery of streptomycin in 1943. In 1946, the American microbiologist John Enders was the first to cultivate viruses in cell cultures, leading the way to the large-scale production of virus cultures for vaccine development. Thousands of scientists have followed these pioneers, each building on the foundation established by his or her predecessors, and each adding an observation that expanded our understanding of microbes and their role in disease. Our knowledge of microbiology is now undergoing a remarkable transformation founded in the rapid technologic advances in genome analysis. The Human Genome Project was a multinational program that concluded in 2005 with the comprehensive sequencing of the human genome. The techniques developed for this program have rapidly moved into the research and clinical laboratories, leading to microbial sequencing and revealing previously unappreciated insights about pathogenic properties of organisms, taxonomic relationships, and functional attributes of the endogenous microbial population. Clearly, we are at the early stages of novel approaches to diagnostics and therapeutics based on the monitoring and manipulations of this population (the microbiome). The world that van Leeuwenhoek discovered was complex, consisting of protozoa and bacteria of all shapes and sizes. However, the complexity of medical microbiology we know today rivals the limits of the imagination. We now know that there are thousands of different types of microbes that live in, on, and around us and hundreds that cause serious human diseases. To understand this information and organize it in a useful manner, it is important to understand some of the basic aspects of medical microbiology. To start, the microbes can be subdivided into the following four general groups: viruses, bacteria, fungi, and parasites, each having its own level of complexity. ## Viruses Viruses are the smallest infectious particles, ranging in diameter from 18 to 600 nanometers (most viruses are < 200 nm and cannot be seen with a light microscope). Viruses typically contain either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) but not both; however, some viral-like particles do not contain any detectable nucleic acids (e.g., prions), whereas the recently discovered Mimivirus contains both RNA and DNA. The viral nucleic acids required for replication are enclosed in a protein shell with or without a lipid membrane coat. Viruses are true parasites, requiring host cells for replication. The cells they infect and the host response to the infection dictate the nature of the clinical manifestation. More than 2000 species of viruses have been described, with approximately 650 infecting humans and animals. Infection can lead either to rapid replication and destruction of the cell or to a long-term chronic relationship with possible integration of the viral genetic information into the host genome. The factors that determine which of these takes place are only partially understood. For example, infection with the human immunodeficiency virus, the etiologic agent of the acquired immunodeficiency syndrome (AIDS), can result in the latent infection of CD4 lymphocytes or the active replication and destruction of these immunologically important cells. Likewise, infection can spread to other susceptible cells, such as the microglial cells of the brain, resulting in the neurologic manifestations of AIDS. The virus determines the disease and can range from the common cold to gastroenteritis to fatal catastrophes such as rabies, Ebola, smallpox, or AIDS. ## Bacteria Bacteria are relatively simple in structure. They are prokaryotic organisms-simple unicellular organisms with no nuclear membrane, mitochondria, Golgi bodies, or endoplasmic reticulum-that reproduce by asexual division. The bacterial cell wall is complex, consisting of one of two basic forms: a gram-positive cell wall with a thick peptidoglycan layer, and a gram-negative cell wall with a thin peptidoglycan layer and an overlying outer membrane. Some bacteria lack this cell wall structure and compensate by surviving only inside host cells or in a hypertonic environment. The size (1 to 20 μm or larger), shape (spheres, rods, spirals), and spacial arrangement (single cells, chains, clusters) of the cells are used for the preliminary classification of bacteria, and the phenotypic and genotypic properties of the bacteria form the basis for the definitive classification. The human body is inhabited by thousands of different bacterial species-some living transiently, others in a permanent parasitic relationship. Likewise, the environment that surrounds us, including the air we breathe, water we drink, and food we eat, is populated with bacteria, many of which are relatively avirulent and some of which are capable of producing life-threatening disease. Disease can result from the toxic effects of bacterial products (e.g., toxins) or when bacteria invade normally sterile body tissues and fluids. ## Fungi In contrast to bacteria, the cellular structure of fungi is more complex. These are eukaryotic organisms that contain a well-defined nucleus, mitochondria, Golgi bodies, and endoplasmic reticulum. Fungi can exist either in a unicellular form (yeast) that can replicate asexually or in a filamentous form (mold) that can replicate asexually and sexually. Most fungi exist as either yeasts or molds; however, some fungi can assume either morphology. These are known as dimorphic fungi and include such organisms as Histoplasma, Blastomyces, and Coccidioides. ## Parasites Parasites are the most complex microbes. Although all parasites are classified as eukaryotic, some are unicellular and others are multicellular. They range in size from tiny protozoa as small as 4 to 5 µm in diameter (the size of some bacteria) to tapeworms that can measure up to 10 meters in length and arthropods (bugs). Indeed, considering the size of some of these parasites, it is hard to imagine how these organisms came to be classified as microbes. Their life cycles are equally complex, with some parasites establishing a permanent relationship with humans and others going through a series of developmental stages in a progression of animal hosts. One of the difficulties confronting students is not only an understanding of the spectrum of diseases caused by parasites but also an appreciation of the epidemiology of these infections, which is vital for developing a differential diagnosis and an approach to the control and prevention of parasitic infections. ## Immunology It is difficult to discuss human microbiology without also discussing the innate and immune responses to the microbes. Our innate and immune responses evolved to protect us from infection. At the same time, the microbes that live in our bodies as normal flora or disease-causing organisms must be able to withstand or evade these host protections sufficiently long to be able to establish their niche within our bodies or spread to new hosts. The peripheral damage that occurs during the war between the host protections and microbial invaders contributes to or may be the cause of the symptoms of the disease. Ultimately, the innate and immune responses are the best prevention and cure for microbial disease. ## Microbial Disease One of the most important reasons for studying microbes is to understand the diseases they cause and the ways to control them. Unfortunately, the relationship between many organisms and their diseases is not simple. Specifically, most organisms do not cause a single well-defined disease, although there are certainly ones that do (e.g., Clostridium tetani [tetanus], Ebola virus [Ebola], Plasmodium species [malaria]). Instead, it is more common for a particular organism to produce many manifestations of disease (e.g., Staphylococcus aureus-endocarditis, pneumonia, wound infections, food poisoning) or for many organisms to produce the same disease (e.g., meningitis caused by viruses, bacteria, fungi, and parasites). In addition, relatively few organisms can be classified as always pathogenic, although some do belong in this category (e.g., rabies virus, Bacillus anthracis, Sporothrix schenckii, Plasmodium species). Instead, most organisms are able to establish disease only under well-defined circumstances (e.g., introduction of an organism with a potential for causing disease into a normally sterile site such as the brain, lungs, and peritoneal cavity). Some diseases arise when a person is exposed to organisms from external sources. These are known as exogenous infections, and examples include diseases caused by influenza virus, C. tetani, Neisseria gonorrhoeae, Coccidioides immitis, and Entamoeba histolytica. Most human diseases, however, are produced by organisms in the person&#x27;s own microbial flora that spread to normally sterile body sites where disease can ensue (endogenous infections). The interaction between an organism and the human host is complex. The interaction can result in transient colonization, a long-term symbiotic relationship, or disease. The virulence of the organism, the site of exposure, and the host&#x27;s ability to respond to the organism determine the outcome of this interaction. Thus the manifestations of disease can range from mild symptoms to organ failure and death. The role of microbial virulence and the host&#x27;s immunologic response is discussed in depth in subsequent chapters. The human body is remarkably adapted to controlling exposure to pathogenic microbes. Physical barriers prevent invasion by the microbe; innate responses recognize molecular patterns on the microbial components and activate local defenses and specific adapted immune responses that target the microbe for elimination. Unfortunately, the immune response is often too late or too slow. To improve the human body&#x27;s ability to prevent infection, the immune system can be augmented either through the passive transfer of antibodies present in immune globulin preparations or through active immunization with components of the microbes (vaccines). Infections can also be controlled with a variety of chemotherapeutic agents. Unfortunately, microbes can mutate and share genetic information, and those that cannot be recognized by the immune response because of antigenic variation or those that are resistant to antibiotics will be selected and will endure. Thus the battle for control between microbe and host continues, with neither side yet able to claim victory (although the microbes have demonstrated remarkable ingenuity). There clearly is no "magic bullet" that has eradicated infectious diseases. ## Diagnostic Microbiology The clinical microbiology laboratory plays an important role in the diagnosis and control of infectious diseases. However, the ability of the laboratory to perform these functions is limited by the quality of the specimen collected from the patient, the means by which it is transported from the patient to the laboratory, and the techniques used to demonstrate the microbe in the sample. Because most diagnostic tests are based on the ability of the organism to grow, transport conditions must ensure the viability of the pathogen. In addition, the most sophisticated testing protocols are of little value if the collected specimen is not representative of the site of infection. This seems obvious, but many specimens sent to laboratories for analysis are contaminated during collection with the organisms that colonize mucosal surfaces. It is virtually impossible to interpret the testing results with contaminated specimens, because most infections are caused by endogenous organisms. The laboratory is also able to determine the antimicrobial activity of selected chemotherapeutic agents, although the value of these tests is limited. The laboratory must test only organisms capable of producing disease and only medically relevant antimicrobials. To test all isolated organisms or an indiscriminate empirical selection of drugs can yield misleading results with potentially dangerous consequences. Not only can a patient be treated inappropriately with unnecessary antibiotics, but also the true pathogenic organism may not be recognized among the plethora of organisms isolated and tested. Finally, the in vitro determination of an organism&#x27;s susceptibility to a variety of antibiotics is only one aspect of a complex picture. The virulence of the organism, site of infection, and patient&#x27;s ability to respond to the infection influence the host-parasite interaction and must also be considered when planning treatment. ## Summary It is important to realize that our knowledge of the microbial world is evolving continually. Just as the early microbiologists built their discoveries on the foundations established by their predecessors, we and future generations will continue to discover new microbes, new diseases, and new therapies. The following chapters are intended as a foundation of knowledge that can be used to build your understanding of microbes and their diseases.