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How Infection Works

There is a close connection between microbes and humans. Experts believe about half of all human DNA originated from viruses that infected and embedded their nucleic acid in our ancestors’ egg and sperm cells.


Microbes occupy all of our body surfaces, including the skin, gut, and mucous membranes. In fact, our bodies contain at least 10 times more bacterial cells than human ones, blurring the line between where microbes end and humans begin. Microbes in the human gastrointestinal tract alone comprise at least 10 trillion organisms, representing more than 1,000 species, which are thought to prevent the gut from being colonized by disease-causing organisms. Among their other beneficial roles, microbes synthesize vitamins, break down food into absorbable nutrients, and stimulate our immune systems.


The vast majority of microbes establish themselves as persistent “colonists,” thriving in complex communities within and on our bodies. In many cases, the microbes derive benefits without harming us; in other cases, both host and microbe benefit.

From the moment we are born, microbes begin to colonize our bodies. Each of us has a unique set of microbial communities, which are believed to play an important role in digestion and in protection from disease.

From the moment we are born, microbes begin to colonize our bodies. Each of us has a unique set of microbial communities, which are believed to play an important role in digestion and in protection from disease.



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I How Infection Works There is a close Microbes occupy all of our body surfaces, including the connection between skin, gut, and mucous membranes. microbes and humans. In fact, our bodies contain at least 10 times more bacterial cells than human Experts believe about half ones, blurring the line between where microbes of all human DNA originated from end and humans begin. Microbes in the human viruses that infected and embedded gastrointestinal tract alone comprise at least 10 trillion organisms, representing more than 1,000 species, their nucleic acid in our ancestors’ which are thought to prevent the gut from being egg and sperm cells. colonized by disease-causing organisms. Among their other beneficial roles, microbes synthesize vitamins, break down food into absorbable nutrients, and stimulate our immune systems. The vast majority of microbes establish themselves as persistent “colonists,” thriving in complex communities within and on our bodies. In many cases, the microbes derive benefits without harming us; in other cases, both host and microbe benefit. From the moment we are born, microbes begin to colonize our bodies. Each of us has a unique set of microbial communities, which are believed to play an important role in digestion and in protection from disease. 4

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Viruses Lactobacillus bacteria, which produce lactic acid Viruses are tiny, ranging in size from about 20 to to help with digestion. 400 nanometers in diameter (see page 9). Billions can fit on the head of a pin. Some are rod shaped; others are round and 20 sided; and yet others have fanciful forms, with multisided “heads” and cylindrical “tails.” Viruses are simply packets of nucleic acid, either DNA or RNA, And though some microbes make us sick and even surrounded by a protein shell and kill us, in the long run they have a shared interest in sometimes fatty materials called our survival. For these tiny invaders, a dead host is a lipids. Outside a living cell, a dead end. virus is a dormant particle, lacking the raw materials for reproduction. The success of microorganisms is due to their Only when it enters a host cell remarkable adaptability. Through natural selection, does it go into action, hijacking the organisms that are genetically better suited to their cell’s metabolic machinery to produce surroundings have more offspring and transmit copies of itself that may burst out of their desirable traits to future generations. This An electron micrograph of an infected cells or simply bud off a cell process operates far more efficiently in the microbial influenza virus particle, showing membrane. This lack of self-sufficiency world than in people. Humans produce a new details of its structure. means that viruses cannot be cultured generation every 20 years or so; bacteria do it every in artificial media for scientific research 20 to 30 minutes, and viruses even faster. Because or vaccine development; they can be grown only in they reproduce so quickly, microorganisms can living cells, fertilized eggs, tissue cultures, or bacteria. assemble in enormous numbers with great variety in their communities. If their environment suddenly Viruses are responsible for a wide range of diseases, changes, the community’s genetic variations make including the common cold, measles, chicken pox, it more likely that some will survive. This gives genital herpes, and influenza. Many of the emerging microbes a huge advantage over humans when it infectious diseases, such as AIDS and SARS, are comes to adapting for survival. caused by viruses. Types of Microbes Bacteria Bacteria are 10 to 100 times larger than viruses There are five major categories of infectious agents: and are more self-sufficient. These single-celled Viruses, bacteria, fungi, protozoa, and helminths. organisms, generally visible under a low-powered 5

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microscope, come in three shapes: spherical material from other bacteria, viruses, plants, and (coccus), rodlike (bacillus), and curved (vibrio, even yeasts. This ability means they can evolve spirillum, or spirochete). suddenly and rapidly instead of slowly adapting. Most bacteria carry a single circular molecule of Bacteria are ancient organisms. Evidence for them DNA, which encodes (or programs) the essential exists in the fossil record from more than 3 billion genes for reproduction and other cellular functions. years ago. They have evolved many different Sometimes they carry accessory small rings of DNA, behaviors over a wide range of habitats, learning to known as plasmids, that encode for specialized adhere to cells, make paralyzing poisons and other functions like antibiotic resistance. Unlike more toxins, evade or suppress our bodies’ defenses, and complex forms of life, bacteria carry only one set resist drugs and the immune system’s antibodies. of chromosomes instead of two. They reproduce Bacterial infections are associated with diseases such by dividing into two cells, a process called binary as strep throat, tuberculosis, staph skin infections, fission. Their offspring are identical, essentially and urinary tract and bloodstream infections. clones with the exact same genetic material. When mistakes are made during replication and a mutation Other Infectious Agents occurs, it creates variety within the population The other three major types of infectious agents that could—under the right circumstances—lead include fungi (spore-forming organisms that to an enhanced ability to adapt to a changing range from bread mold to ringworm to deadly environment. Bacteria can also acquire new genetic histoplasmosis), protozoa (such as the agents behind malaria and dysentery), and helminths (parasitic worms like those that cause trichinosis, hookworm, and schistosomiasis). A newly recognized class of infectious agents—the prions, or proteinaceous infectious particles—consist only of protein. Prions are thought to cause variant Creutzfeldt-Jakob disease in humans and “mad cow disease” in cattle. These proteins are abnormally folded and, when they come in contact with similar normal proteins, turn them into prions like themselves, setting off a chain reaction that eventually riddles the brain with holes. Prions evoke no immune response and resist heat, ultraviolet light, radiation, and sterilization, making them difficult to control. E. coli bacteria directly transferring genetic material via a pilus (the thin strand connecting the two). 6

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Grand Prismatic Spring, a geothermal hot spring in Yellowstone and home to microbes that have adapted to this extreme environment. settlements has also created transition zones filled Encountering Microbes with opportunities for contact with potential disease- causing agents. Microbes have inhabited the earth for billions of years and may be the earliest life forms on the Human travel and commerce have brought other planet. They live in every conceivable ecological risks. Almost 2 million passengers, each a potential niche—soil, water, air, plants, rocks, and animals. carrier of infection, travel daily by aircraft to They even live in extreme environments, such as international destinations. International commerce, hot springs, deep ocean thermal vents, and Antarctic especially in foodstuffs, adds to the global traffic ice. Indeed microbes, by sheer mass, are the earth’s most abundant life form and are highly adaptable to external forces. New Meeting Places Any changes that create new intersections between microbes and people pave the way for disease- causing agents to enter our species. One such change that has put us at risk is the global human population explosion—from about 1.6 billion people in 1900 to nearly 7 billion today. Humans have cleared forests for agriculture and suburbanization, leading to closer contact with environments that may harbor novel (or newly introduced) pathogens. Through much of the world’s developing tropical regions, the massive expansion of roads and human 7

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of disease-causing microbes. Because the transit times of people and goods are often shorter than the incubation periods of infection, carriers of disease can arrive at their destination before the infection they harbor is detectable. International trade and travel are associated with the emergence of such infectious agents as the SARS coronavirus and West Evidence for why it is important to cover your mouth when you sneeze. Nile virus. Changes in human demographics and behavior are who touches that surface and then touches his or her linked with the emergence of infections such as eye, mouth, or nose. Droplets spread by sneezes, AIDS and hepatitis C, through sexual activity and coughs, or simply talking can transmit disease if they intravenous drug use. More broad-scale changes come in contact with mucous membranes of the eye, that raise the risk of infectious disease include the mouth, or nose of another person. SARS, tuberculosis, breakdown of public health systems, poverty, war, and influenza are examples of diseases spread by and famine. airborne droplet transmission. Common vehicles: Contaminated food, water, Entering the Human Host blood, or other vehicles may spread pathogens. Microorganisms capable of causing disease— Microorganisms like E. coli and Salmonella enter pathogens—usually enter our bodies through the digestive system in this manner. the mouth, eyes, nose, or urogenital openings, or through wounds or Vectors: Creatures such as fleas, mites, bites that breach the skin barrier. ticks, rats, snails, and dogs—called Organisms can spread—or be vectors—can also transmit disease. transmitted—by several routes. The most common vector for human infection is the mosquito, which Contact: Some diseases spread via transmits malaria, West Nile virus, and direct contact with infected skin, yellow fever. mucous membranes, or body fluids. Diseases transmitted this way include Airborne transmission: Pathogens can also cold sores (herpes simplex virus type 1) and spread when residue from evaporated droplets sexually transmitted diseases such as AIDS. Pathogens or dust particles containing microorganisms are can also be spread by indirect contact when an suspended in air for long periods of time. Diseases infected person touches a surface such as a doorknob, spread by airborne transmission include measles countertop, or faucet handle, leaving behind and hantavirus pulmonary syndrome. microbes that are then transferred to another person 8

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HOW TINY ARE MICROBES? Bacteria and viruses are almost unimaginably small. Bacteria are usually measured in microns (abbreviated “µm,” 1 micron equals 1 one- millionth of a meter), while viruses are measured [1-1.2 µm long, in the even more miniscule unit of nanometers including tail] (abbreviated “nm,” 1 nanometer equals 1 one- billionth of a meter, or 1 one-thousandth of a micron). To give a sense of these measures, consider that the period at the end of this sentence is about 350 microns, or 350,000 nanometers, in diameter. If we magnify the period to one thousand times its actual size (see far left), a nearby Pseudomonas aeruginosa, the bacterium that causes hospital-acquired pneumonia and bloodstream infections, becomes visible. If, in turn, we magnify Pseudomonas 75 more times, or to 75,000 times its actual size, an adjacent influenza virus particle also becomes visible. symptoms that make a person suffer during an How Pathogens Make Us Sick infection—fever, malaise, headache, rash—result from the activities of the immune system trying to eliminate Infection does not necessarily lead to disease. the infection from the body. Infection occurs when viruses, bacteria, or other microbes enter your body and begin to multiply. Pathogenic microbes challenge the immune system Disease, which typically happens in a small in many ways. Viruses make us sick by killing proportion of infected people, occurs when the cells cells or disrupting cell function. Our bodies often in your body are damaged as a result of infection, respond with fever (heat inactivates many viruses), and signs and symptoms of an illness appear. the secretion of a chemical called interferon (which blocks viruses from reproducing), or by marshaling In response to infection, your immune system the immune system’s antibodies and other cells to springs into action. White blood cells, antibodies, target the invader. Many bacteria make us sick the and other mechanisms go to work to rid your same way, but they also have other strategies at their body of the foreign invader. Indeed, many of the disposal. Sometimes bacteria multiply so rapidly they 9

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• Histoplasma capsulatum, a fungus that transmits histoplasmosis, grows in soil contaminated with bird or bat droppings. Spores of the fungus emerge from disturbed soil and, once inhaled into the lungs, germinate and transform into budding yeast cells. In its acute phase, the disease causes coughing and flu-like symptoms. Sometimes histoplasmosis affects multiple organ systems and can be fatal unless treated. • The protozoa that cause malaria, which are members of the genus Plasmodium, have complex life cycles. Sporozoites, a cell type that infects new hosts, develop in the salivary glands of Anopheles mosquitos. They leave the mosquito during a blood A fever is often part of the immune system’s response to infection. meal, enter the host’s liver, and multiply. Cells infected with sporozoites eventually burst, releasing another cell form, merozoites, into the bloodstream. crowd out host tissues and disrupt normal function. These cells infect red blood cells and then rapidly Sometimes they kill cells and tissues outright. reproduce, destroying the red blood cell hosts Sometimes they make toxins that can paralyze, destroy and releasing many new merozoites to do further cells’ metabolic machinery, or precipitate a massive damage. Most merozoites continue to reproduce in immune reaction that is itself toxic. this way, but some differentiate into sexual forms (gametocytes) that are taken up by the female Other classes of microbes attack the body in mosquito, thus completing the protozoan life cycle. different ways: • Trichinella spiralis, the helminth that causes trichinosis, enters the body encased in cysts residing in undercooked meat. Pepsin and hydrochloric acid in our bodies help free the larvae in the cysts to These and many other ingenious pathways enter the small intestine, where they molt, mature, to causing disease demonstrate pathogens’ and ultimately produce more larvae that pass rich evolutionary legacy and their continued through the intestine and into the bloodstream. At inventiveness. In the next section, we look more that point they are free to reach various organs. closely at how some of these organisms have learned Those that reach skeletal muscle cells can survive to thrive—often at humans’ expense. and form new cysts, thus completing their life cycle. 10