Julianne Zedalis; John Eggebrecht

Learning Objectives

In this section, you will explore the following questions:

What are examples of bacterial diseases that caused historically important plagues and epidemics?
What are links between bacteria, especially in biofilms, and foodborne diseases?
How can the overuse of antibiotics create “super bugs” such as MRSA?

Connection for AP^® Courses

Although many bacteria participate in mutualistic relationships with their hosts, others exist in parasitic relationships, causing disease. Many bacteria have evolved resistance to antibiotics, and scientists are developing new antibiotics that are effective against infections caused by emergent diseases. Examples of bacteria-caused infections include pneumonia, plague, typhoid, and Lyme disease. Although some diseases have been eradicated, the emergence of new infections, such as MRSA, provides evidence that evolution is an ongoing process. Epidemiologists study how disease affects a population.

Information presented and the examples highlighted in the section support concepts outlined in Big Idea 1 and Big Idea 3 of the AP^® Biology Curriculum Framework. The AP^® Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP^® Biology course, an inquiry-based laboratory experience, instructional activities, and AP^® exam questions. A learning objective merges required content with one or more of the seven science practices.

Big Idea 1	The process of evolution drives the diversity and unity of life.
Enduring Understanding 1.C	Life continues to evolve within a changing environment.
Essential Knowledge	1.C.3 Scientific evidence supports the idea that evolution in all organisms, including prokaryotes, continues to occur.
Science Practice	1.2 The student can describe representations and models of natural or man-made phenomena and systems in the domain.
Learning Objective	1.25 The student is able to describe a model that represents evolution within a population.
Essential Knowledge	1.C.3 Scientific evidence supports the idea that evolution in all organisms, including prokaryotes, continues to occur.
Science Practice	5.3 The student can evaluate the evidence provided by data sets in relation to a particular scientific question.
Learning Objective	1.26 The student is able to evaluate given data sets that illustrate evolution as an ongoing process.
Big Idea 3	Living systems store, retrieve, transmit and respond to information essential to life processes.
Enduring Understanding 2.C	Organisms use feedback mechanisms to regulate growth and reproduction, and to maintain dynamic homeostasis.
Essential Knowledge	3.C.1 Genetic changes that affect phenotypes are subject to selection.
Science Practice	6.4 The student can make claims and predictions about natural phenomena based on scientific theories and models.
Science Practice	7.2 The student can connect concepts in and across domain(s) to generalize or extrapolate in and/or across enduring understandings and/or big ideas.
Learning Objective	3.24 The student is able to predict how a change in genotype, when expressed as a phenotype, provides a variation that is subject to natural selection.

The Science Practice Challenge Questions contain additional test questions for this section that will help you prepare for the AP exam. These questions address the following standards:
[APLO 3.3][APLO 3.27][APLO 2.8][APLO 2.9][APLO 2.24][APLO 4.14][APLO 4.21]

Devastating pathogen-borne diseases and plagues, both viral and bacterial in nature, have affected humans since the beginning of human history. The true cause of these diseases was not understood at the time, and some people thought that diseases were a spiritual punishment. Over time, people came to realize that staying apart from afflicted persons, and disposing of the corpses and personal belongings of victims of illness, reduced their own chances of getting sick.

Epidemiologists study how diseases affect a population. An epidemic is a disease that occurs in an unusually high number of individuals in a population at the same time. A pandemic is a widespread, usually worldwide, epidemic. An endemic disease is a disease that is constantly present, usually at low incidence, in a population.

Long History of Bacterial Disease

There are records about infectious diseases as far back as 3000 B.C. A number of significant pandemics caused by bacteria have been documented over several hundred years. Some of the most memorable pandemics led to the decline of cities and nations.

In the 21^st century, infectious diseases remain among the leading causes of death worldwide, despite advances made in medical research and treatments in recent decades. A disease spreads when the pathogen that causes it is passed from one person to another. For a pathogen to cause disease, it must be able to reproduce in the host’s body and damage the host in some way.

The Plague of Athens

In 430 B.C., the Plague of Athens killed one-quarter of the Athenian troops that were fighting in the great Peloponnesian War and weakened Athens’ dominance and power. The plague impacted people living in overcrowded Athens as well as troops aboard ships that had to return to Athens. The source of the plague may have been identified recently when researchers from the University of Athens were able to use DNA from teeth recovered from a mass grave. The scientists identified nucleotide sequences from a pathogenic bacterium, Salmonella enterica serovar Typhi (Figure 22.20), which causes typhoid fever.³ This disease is commonly seen in overcrowded areas and has caused epidemics throughout recorded history.

Micrograph shows pink rod-shaped bacteria.

Figure 22.20 Salmonella enterica serovar Typhi, the causative agent of Typhoid fever, is a Gram-negative, rod-shaped gamma protobacterium. Typhoid fever, which is spread through feces, causes intestinal hemorrhage, high fever, delirium and dehydration. Today, between 16 and 33 million cases of this re-emerging disease occur annually, resulting in over 200,000 deaths. Carriers of the disease can be asymptomatic. In a famous case in the early 1900s, a cook named Mary Mallon unknowingly spread the disease to over fifty people, three of whom died. Other Salmonella serotypes cause food poisoning. (credit: modification of work by NCI, CDC)

Bubonic Plagues

From 541 to 750, an outbreak of what was likely a bubonic plague (the Plague of Justinian), eliminated one-quarter to one-half of the human population in the eastern Mediterranean region. The population in Europe dropped by 50 percent during this outbreak. Bubonic plague would strike Europe more than once.

One of the most devastating pandemics was the Black Death (1346 to 1361) that is believed to have been another outbreak of bubonic plague caused by the bacterium Yersinia pestis. It is thought to have originated initially in China and spread along the Silk Road, a network of land and sea trade routes, to the Mediterranean region and Europe, carried by rat fleas living on black rats that were always present on ships. The Black Death reduced the world’s population from an estimated 450 million to about 350 to 375 million. Bubonic plague struck London hard again in the mid-1600s (Figure 22.21). In modern times, approximately 1,000 to 3,000 cases of plague arise globally each year. Although contracting bubonic plague before antibiotics meant almost certain death, the bacterium responds to several types of modern antibiotics, and mortality rates from plague are now very low.

Illustration A shows two men loading a dead body onto a cart. Another body lies in the street. Label beneath the illustration says, “Plague in 1665.” Micrograph B shows rod-shaped bacteria. Photo C shows a man with black gangrene on his fingers, arm, nose and lips.

Figure 22.21 The (a) Great Plague of London killed an estimated 200,000 people, or about twenty percent of the city’s population. The causative agent, the (b) bacterium Yersinia pestis, is a Gram-negative, rod-shaped bacterium from the class Gamma Proteobacteria. The disease is transmitted through the bite of an infected flea, which is infected by a rodent. Symptoms include swollen lymph nodes, fever, seizure, vomiting of blood, and (c) gangrene. (credit b: Rocky Mountain Laboratories, NIAID, NIH; scale-bar data from Matt Russell; credit c: Textbook of Military Medicine, Washington, D.C., U.S. Dept. of the Army, Office of the Surgeon General, Borden Institute)

Link to Learning

Watch a video on the modern understanding of the Black Death—bubonic plague in Europe during the 14^th century.

How were researchers able to use modern science to determine the agent of disease for the bubonic plague of the 14th century?

The amino acid sequence of proteins, extracted from the samples taken from skeletons buried in a cemetery from the 14th century, was constructed and compared to that of modern strain of the bacterium Y. enterocolitica and found a close match.
The genomic sequence of the DNA, extracted from the samples taken from skeletons buried in a cemetery from the 14th century, was constructed and compared to that of modern strain of the bacterium Y. enterocolitica and found a close match.
The gene sequence of 16S rRNA, extracted from the samples taken from skeletons buried in a cemetery from the 14th century, was constructed and compared to that of modern strain of the bacterium Y. pestis and found a close match.
The genomic sequence of the DNA, extracted from the samples taken from skeletons buried in a cemetery from the 14th century, was constructed and compared to that of modern strain of the bacterium Y. pestis and found a close match.

Migration of Diseases to New Populations

Over the centuries, Europeans tended to develop genetic immunity to endemic infectious diseases, but when European conquerors reached the western hemisphere, they brought with them disease-causing bacteria and viruses, which triggered epidemics that completely devastated populations of Native Americans, who had no natural resistance to many European diseases. It has been estimated that up to 90 percent of Native Americans died from infectious diseases after the arrival of Europeans, making conquest of the New World a foregone conclusion.

Emerging and Re-emerging Diseases

The distribution of a particular disease is dynamic. Therefore, changes in the environment, the pathogen, or the host population can dramatically impact the spread of a disease. According to the World Health Organization (WHO) an emerging disease (Figure 22.22) is one that has appeared in a population for the first time, or that may have existed previously but is rapidly increasing in incidence or geographic range. This definition also includes re-emerging diseases that were previously under control. Approximately 75 percent of recently emerging infectious diseases affecting humans are zoonotic diseases, zoonoses, diseases that primarily infect animals and are transmitted to humans; some are of viral origin and some are of bacterial origin. Brucellosis is an example of a prokaryotic zoonosis that is re-emerging in some regions, and necrotizing fasciitis (commonly known as flesh-eating bacteria) has been increasing in virulence for the last 80 years for unknown reasons.

Emerging or re-emerging bacterial diseases are shown on a world map. Multidrug-resistant tuberculosis is emerging in North America, Europe, and Asia. Vancomycin-resistant Staphylococcus aureus and E. coli O157:H7 are emerging in North America and East Asia. Lyme disease is spreading in North America. Cholera is emerging in Africa and South America. Diptheria and typhoid fever are re-emerging in Asia.

Figure 22.22 The map shows regions where bacterial diseases are emerging or reemerging. (credit: modification of work by NIH)

Some of the present emerging diseases are not actually new, but are diseases that were catastrophic in the past (Figure 22.23). They devastated populations and became dormant for a while, just to come back, sometimes more virulent than before, as was the case with bubonic plague. Other diseases, like tuberculosis, were never eradicated but were under control in some regions of the world until coming back, mostly in urban centers with high concentrations of immunocompromised people. The WHO has identified certain diseases whose worldwide re-emergence should be monitored. Among these are two viral diseases (dengue fever and yellow fever), and three bacterial diseases (diphtheria, cholera, and bubonic plague). The war against infectious diseases has no foreseeable end.

Part A shows the red, bullseye-shaped rash of a person infected with Borrelia. Part B shows a micrograph of Borrelia, which look like tiny corkscrews. Part C shows the life cycle of the bacteria, which begins when Borrelia infect a tick egg. The egg hatches into larva, which feeds on a mouse, then into a nymph, which also feeds on a mouse. The nymph feeds again, this time on a deer, or sometimes a human.

Figure 22.23 Lyme disease often, but not always, results in (a) a characteristic bullseye rash. The disease is caused by a (b) Gram-negative spirochete bacterium of the genus Borrelia. The bacteria (c) infect ticks, which in turns infect mice. Deer are the preferred secondary host, but the ticks also may feed on humans. Untreated, the disease causes chronic disorders in the nervous system, eyes, joints, and heart. The disease is named after Lyme, Connecticut, where an outbreak occurred in 1995 and has subsequently spread. The disease is not new, however. Genetic evidence suggests that Ötzi the Iceman, a 5,300-year-old mummy found in the Alps, was infected with Borrelia. (credit a: James Gathany, CDC; credit b: CDC; scale-bar data from Matt Russell)

Biofilms and Disease

Recall that biofilms are microbial communities that are very difficult to destroy. They are responsible for diseases such as infections in patients with cystic fibrosis, Legionnaires’ disease, and otitis media. They produce dental plaque and colonize catheters, prostheses, transcutaneous and orthopedic devices, contact lenses, and internal devices such as pacemakers. They also form in open wounds and burned tissue. In healthcare environments, biofilms grow on hemodialysis machines, mechanical ventilators, shunts, and other medical equipment. In fact, 65 percent of all infections acquired in the hospital (nosocomial infections) are attributed to biofilms. Biofilms are also related to diseases contracted from food because they colonize the surfaces of vegetable leaves and meat, as well as food-processing equipment that isn’t adequately cleaned.

Biofilm infections develop gradually; sometimes, they do not cause symptoms immediately. They are rarely resolved by host defense mechanisms. Once an infection by a biofilm is established, it is very difficult to eradicate, because biofilms tend to be resistant to most of the methods used to control microbial growth, including antibiotics. Biofilms respond poorly or only temporarily to antibiotics; it has been said that they can resist up to 1,000 times the antibiotic concentrations used to kill the same bacteria when they are free-living or planktonic. An antibiotic dose that large would harm the patient; therefore, scientists are working on new ways to get rid of biofilms.

Antibiotics: Are We Facing a Crisis?

The word antibiotic comes from the Greek anti meaning “against” and bios meaning “life.” An antibiotic is a chemical, produced either by microbes or synthetically, that is hostile to the growth of other organisms. Today’s news and media often address concerns about an antibiotic crisis. Are the antibiotics that easily treated bacterial infections in the past becoming obsolete? Are there new “superbugs”—bacteria that have evolved to become more resistant to our arsenal of antibiotics? Is this the beginning of the end of antibiotics? All these questions challenge the healthcare community.

One of the main causes of resistant bacteria is the abuse of antibiotics. The imprudent and excessive use of antibiotics has resulted in the natural selection of resistant forms of bacteria. The antibiotic kills most of the infecting bacteria, and therefore only the resistant forms remain. These resistant forms reproduce, resulting in an increase in the proportion of resistant forms over non-resistant ones. Another major misuse of antibiotics is in patients with colds or the flu, for which antibiotics are useless. Another problem is the excessive use of antibiotics in livestock. The routine use of antibiotics in animal feed promotes bacterial resistance as well. In the United States, 70 percent of the antibiotics produced are fed to animals. These antibiotics are given to livestock in low doses, which maximize the probability of resistance developing, and these resistant bacteria are readily transferred to humans.

Link to Learning

Visit this site to learn more about the problem of routine antibiotic administration to livestock and antibiotic-resistant bacteria.

In your own words, what is the problem with administering antibiotics to livestock when they are not in need of them?

Development of antibiotic-susceptible bacteria that can be transferred to humans, and their presence makes treatment of disease with antibiotics (in animals or humans) much more difficult.
Development of antibiotic-resistant bacteria that cannot be transferred to humans, and their presence makes treatment of disease with antibiotics (in animals or humans) much more difficult.
Development of antibiotic-resistant bacteria that can be transferred to humans, and their presence makes treatment of disease with antibiotics (in animals or humans) much more difficult.
Development of antibiotic-susceptible bacteria that cannot be transferred to humans, and their presence makes treatment of disease with antibiotics (in animals or humans) much more difficult.

One of the Superbugs: MRSA

The imprudent use of antibiotics has paved the way for bacteria to expand populations of resistant forms. For example, Staphylococcus aureus, often called “staph,” is a common bacterium that can live in the human body and is usually easily treated with antibiotics. A very dangerous strain, however, methicillin-resistant Staphylococcus aureus (MRSA) has made the news over the past few years (Figure 22.24). This strain is resistant to many commonly used antibiotics, including methicillin, amoxicillin, penicillin, and oxacillin. MRSA can cause infections of the skin, but it can also infect the bloodstream, lungs, urinary tract, or sites of injury. While MRSA infections are common among people in healthcare facilities, they have also appeared in healthy people who haven’t been hospitalized but who live or work in tight populations (like military personnel and prisoners). Researchers have expressed concern about the way this latter source of MRSA targets a much younger population than those residing in care facilities. The Journal of the American Medical Association reported that, among MRSA-afflicted persons in healthcare facilities, the average age is 68, whereas people with “community-associated MRSA” (CA-MRSA) have an average age of 23.⁴

The micrograph shows clusters of round bacteria clinging to a surface. Each bacterium is about 0.4 microns across.

Figure 22.24 This scanning electron micrograph shows methicillin-resistant Staphylococcus aureus bacteria, commonly known as MRSA. S. aureus is not always pathogenic, but can cause diseases such as food poisoning and skin and respiratory infections. (credit: modification of work by Janice Haney Carr; scale-bar data from Matt Russell)

In summary, the medical community is facing an antibiotic crisis. Some scientists believe that after years of being protected from bacterial infections by antibiotics, we may be returning to a time in which a simple bacterial infection could again devastate the human population. Researchers are developing new antibiotics, but it takes many years to of research and clinical trials, plus financial investments in the millions of dollars, to generate an effective and approved drug.

Foodborne Diseases

Prokaryotes are everywhere: They readily colonize the surface of any type of material, and food is not an exception. Most of the time, prokaryotes colonize food and food-processing equipment in the form of a biofilm. Outbreaks of bacterial infection related to food consumption are common. A foodborne disease (colloquially called “food poisoning”) is an illness resulting from the consumption the pathogenic bacteria, viruses, or other parasites that contaminate food. Although the United States has one of the safest food supplies in the world, the U.S. Centers for Disease Control and Prevention (CDC) has reported that “76 million people get sick, more than 300,000 are hospitalized, and 5,000 Americans die each year from foodborne illness.”

The characteristics of foodborne illnesses have changed over time. In the past, it was relatively common to hear about sporadic cases of botulism, the potentially fatal disease produced by a toxin from the anaerobic bacterium Clostridium botulinum. Some of the most common sources for this bacterium were non-acidic canned foods, homemade pickles, and processed meat and sausages. The can, jar, or package created a suitable anaerobic environment where Clostridium could grow. Proper sterilization and canning procedures have reduced the incidence of this disease.

While people may tend to think of foodborne illnesses as associated with animal-based foods, most cases are now linked to produce. There have been serious, produce-related outbreaks associated with raw spinach in the United States and with vegetable sprouts in Germany, and these types of outbreaks have become more common. The raw spinach outbreak in 2006 was produced by the bacterium E. coli serotype O157:H7. A serotype is a strain of bacteria that carries a set of similar antigens on its cell surface, and there are often many different serotypes of a bacterial species. Most E. coli are not particularly dangerous to humans, but serotype O157:H7 can cause bloody diarrhea and is potentially fatal.

All types of food can potentially be contaminated with bacteria. Recent outbreaks of Salmonella reported by the CDC occurred in foods as diverse as peanut butter, alfalfa sprouts, and eggs. A deadly outbreak in Germany in 2010 was caused by E. coli contamination of vegetable sprouts (Figure 22.25). The strain that caused the outbreak was found to be a new serotype not previously involved in other outbreaks, which indicates that E. coli is continuously evolving.

Photo A shows round green seeds with stems sprouting from them. Sketch B shows normal, disk-shaped red blood cells on the left. On the right, many of the red blood cells are sickle-shaped.

Figure 22.25 (a) Vegetable sprouts grown at an organic farm were the cause of an (b) E. coli outbreak that killed 32 people and sickened 3,800 in Germany in 2011. The strain responsible, E. coli O104:H4, produces Shiga toxin, a substance that inhibits protein synthesis in the host cell. The toxin (c) destroys red blood cells resulting in bloody diarrhea. Deformed red blood cells clog the capillaries of the kidney, which can lead to kidney failure, as happened to 845 patients in the 2011 outbreak. Kidney failure is usually reversible, but some patients experience kidney problems years later. (credit c: NIDDK, NIH)

Career Connection

Epidemiologist

Epidemiology is the study of the occurrence, distribution, and determinants of health and disease in a population. It is, therefore, part of public health. An epidemiologist studies the frequency and distribution of diseases within human populations and environments.

Epidemiologists collect data about a particular disease and track its spread to identify the original mode of transmission. They sometimes work in close collaboration with historians to try to understand the way a disease evolved geographically and over time, tracking the natural history of pathogens. They gather information from clinical records, patient interviews, surveillance, and any other available means. That information is used to develop strategies, such as vaccinations (Figure 22.26), and design public health policies to reduce the incidence of a disease or to prevent its spread. Epidemiologists also conduct rapid investigations in case of an outbreak to recommend immediate measures to control it.

An epidemiologist has a bachelor’s degree, plus a master’s degree in public health (MPH). Many epidemiologists are also physicians (and have an M.D.), or they have a Ph.D. in an associated field, such as biology or microbiology.

This photo shows syringes, adhesive bandages, and alcohol swabs.

Figure 22.26 Vaccinations can slow the spread of communicable diseases. (credit: modification of work by Daniel Paquet)

Science Practice Connection for AP® Courses

Think About It

How can a strain of bacteria that was previously sensitive to an antibiotic become resistant to the same antibiotic? Why has this become a major global problem?

Teacher Support

Antibiotic resistance develops as a selective pressure (antibiotics in the environment) is placed on a population, driving evolution of the population. This question is an application of AP^® Learning Objective 1.25 and Science Practice 1.2 and Learning Objective 3.24 and Science Practices 6.4 and 7.2 because based on a model you are making a prediction about how a genetic change can result in a change in phenotype (i.e., antibiotic resistance) that is subject to natural selection, providing evidence that evolution continues to occur.

Footnotes

3Papagrigorakis MJ, Synodinos PN, and Yapijakis C. Ancient typhoid epidemic reveals possible ancestral strain of Salmonella enterica serovar Typhi. Infect Genet Evol 7 (2007): 126–7, Epub 2006 Jun.
4Naimi, TS, LeDell, KH, Como-Sabetti, K, et al. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA 290 (2003): 2976–84, doi: 10.1001/jama.290.22.2976.

22.4 Bacterial Diseases in Humans