UPDATED: 10/29/99 UPDATED: 10/29/99 
MICROBIOLOGY | CHEMISTRY | MEDICAL
Teeth, Flossing and Heart Disease, Meningitis: Big Threat on Campus?;
The universal principle of molecular recognition. Biological molecules interact by recognizing and binding with one another in a highly specific manner. Pairs of molecules that interact in this way are called RECEPTORS or BINDING SITES and LIGANDS respectively. Specific regions of atoms (molecular domains) on a receptor molecule have the characteristic of binding or attaching (docking) specifically to unique molecular domains on specific ligands. Following this binding something happens depending on the system involved. In this chapter you will learn how microbes produce disease by recognizing their specific hosts and by producing substances that interact specifically with host receptors to cause disease. Permission to use this cartoon was granted by Sigma Chemical Co.
The learning goals of this section are:
To understand the nature of disease,
particularly infectious disease.
To learn the ways bacteria have of
invading and producing the disease state.
EXTRA CREDIT COMMENTARY 14A: Read the following article at this site. Find 3 articles (on different subjects) in the newspapers or news magazines in the last 12 months that relate to the information presented in this article and discuss these relationships briefly. |
During my all-too-brief lifetime I have seen us go from a state of virtual defenselessness against many infectious bacteria and viruses, where, outside of immunization, prayer, occasional surgery and TLC (tender-loving-care), there was little medically we could do about bacterial infections, to an era of optimistic arrogance where we claimed VICTORY over ALL BACTERIAL INFECTIONS, to the recognition today that this battle is going to go on for the indefinite future and that there is some question now as to the eventual OUTCOME.
In spite of our considerable knowledge about diseases most people in undeveloped countries still die of the same infectious diseases that killed their ancestors 10,000 years ago and that are mostly PREVENTABLE. The WHO estimates that approximately 15 million CHILDREN die each year of preventable infectious disease.
An infectious disease agent must be able to grow on or in a host and it must do harm to that host. Every infectious disease is characterized by the SYMPTOMS produced in the average victim of that infectious disease. These symptoms, referred to as the CLINICAL SYMPTOMS, are used by physicians and health care personnel to identify a particular infectious disease or group of infectious diseases. For example, one set of symptoms identify common upper respiratory diseases (colds). However, the mumps virus has a UNIQUE set of symptoms that are used in diagnosing this particular infectious agent. That is, a single pathogen may produce a clear set of symptoms that allows its easy recognition, whereas a set of identical symptoms (e.g. the "runs", colds, pneumonia) may be produced by a number of different infectious disease agents. Finally, some infectious disease agents cause a variety of different symptoms in different hosts of the same species; AIDS and tuberculosis are two such examples.
In describing an infectious disease the agent is identified, if known, the symptoms are described, along with the prognosis and the manner in which the infectious disease is contracted. Molecular biology has given us tools to rapidly identify the probable etiological agent of many common diseases. The combination of DNA fingerprinting and #PCR make it possible to obtain an accurate diagnosis from as little as 10 microliters of a patient's body fluid (blood, urine, spit, etc.) within a few hours rather than the days it has taken in the recent past. The use of fluorescent-labeled antibodies allow organisms in body fluids and tissues to be detected (identified) in a few minutes or less. New techniques (biochips) are in the pipeline that will cut diagnosis time down to a FEW SECONDS in many cases. While it is crucial, diagnosis only IDENTIFIES the etiological agent, but it does not explain how the disease process works or how the patient contacted the infectious disease agent in the first place. To see what are the most likely diseases YOU MAY SUFFER FROM visit this site.
WHAT
IS A BIOCHIP? |
Before a pathogen can cause a disease its host must be EXPOSED or come into physical contact with a pathogen or its toxic products. The transmission of disease-producing agents within populations is a PUBLIC HEALTH CONCERN which we will deal in Chapter 14 where the science of #EPIDEMIOLOGY is described. An infectious pathogen must be presented to its host in a way that will allow it to grow in/on the host in an environment where it can cause a disease. The bacterium Staphylococcus aureus frequently lives harmlessly in the #nose and on the skin. However, if there is a break in the skin, or if it gets into the proper food, S. aureus can cause #serious disease. Similarly, a break in the vaginal or anal mucus membranes allows the entry of a STD infectious agent that might otherwise not gain a foothold. The pathogenic E. coli strain #O157:H7 is harmless if it is rubbed on your skin, but if ingested in an undercooked hamburger or other food it can reach your intestine where it can grow, causing its host to die, or survive with seriously damaged kidneys and a few feet less of your intestine. Similarly, the toxin of the food-borne pathogen Clostridium botulinum must be delivered in a way that will allow it to be absorbed into the blood of the victim.
HOW Bordetella pertussis
CAUSES WHOOPING COUGH? |
Once introduced into a suitable environment, infectious agents begin to grow. At this point the non-specific defense systems of the body often eliminates the intruders without harm, but if the pathogen has the proper arsenal of weapons it may establish itself and render serious harm on the host. The experimental questions scientists ask today are about the mechanisms that a pathogen employs to establish itself and produce the subsequent disease. These disease-inducing factors are called VIRULENCE FACTORS or VIRULENCE DETERMINANTS. Identification of a pathogen's virulence determinants and an understanding of their molecular mechanisms of action, allows us to design ways to neutralize or destroy the virulence determinants, thus rendering the pathogen harmless; i.e., we can "pull its teeth"or otherwise "neutralize" it.
MAJOR BACTERIAL VIRULENCE DETERMINANTS |
|
TOXINS: Toxins are products of a
pathogen that destroy/damage/inactivate one or more vital component of the host thus allowing the pathogen to survive
and flourish. EXOTOXINS
are toxins that are SECRETED from the cell or leak out of the cell after it dies. Generally they are soluble
proteins and thus are carried throughout the body in the blood or lymph, doing damage at a
distance from the infection site. Toxins tend to target specific cells in the body. Some
are enzymes and others are proteins that bind to and inhibit crucial cellular activities
which eventually lead to the death of cells. A special group of toxins, produced only by
G- bacteria, are called ENDOTOXINS or #LPS. Examples of toxic virulence determinants
include:
Diphtheria
toxin: an enzyme that blocks protein synthesis in many cells. The
bacterium producing this potent toxin grows mainly in the throat. Toxin production only
occurs if the bacterium is infected with a certain bacteriophage. Botulism
Toxin: Inhibits acetylcholine release from motor nerve endings and kills
the nerve cells. As will be discussed in the section on "#Food
Borne Diseases", this is the most deadly toxin known. This is an exception to the
"infection rule", since C. botulinum does not have to infect for
the toxin to kill (however, it can infect grow and produce lethal toxin doses in babies).
Toxin production only occurs if the bacterium is infected with a certain bacteriophage
(different from the diphtheria toxin). Tetanus
toxin: Blocks the function of certain nerve cells which leads to spastic
paralysis in the host. The bacterium that produces this toxin is anaerobic & usually
grows locally in a puncture wound, such as that from a nail or rose thorn, yet it readily
kills full grown horses or humans. Endotoxins are composed of #LPS which is only produced by G- bacteria. Endotoxins have a
general basic structure, but differ significantly in composition between species.
Endotoxins are released in relatively small amounts as the cells grow, but in copious
amounts when the cells die. Different endotoxins differ in their degree of toxicity, but
all are heat stable and can tolerate autoclaving. Endotoxins harm many systems in the body
and hence are very dangerous. They are often responsible for the cause of death of
infections by G- cells. Exotoxin
B: This is a cysteine protease produced by the FLESH
EATING STREPS that dissolves the material between cells. These streps
can move through the tissue at the rate of an inch per hour and antibiotics
do not reach them efficiently. Other toxins are released and the tissue
dies, sloughs off, tissue fluid and blood leaks out, spreading the infection
and the combination of toxins and trauma leads to death. In an attempt to
save patients doctor cut off limbs and large areas of flesh in an effort to
remove the microbes.Most exotoxins are destroyed by heating to 100oC, but some like those of #S. aureus food poisoning are resistant to boiling. Some toxins can be converted to TOXOIDS which are no longer toxic, but can stimulate #ANTIBODY PRODUCTION against the toxin. In general the toxins are so powerful that only minimal growth of the producing bacterium is required to effect the disease and the toxin can exert its effects in the absence of the bacterium that produced it.
ENZYMES: Pathogens use a variety
of enzymes to assist them in establishing infection and producing a disease. There are
virulence determinant enzymes that dissolve the glue between cells, thus allowing the
bacteria to spread rapidly through the tissue. There are enzymes (hemolysins) that #lyse red blood cells and others that lyse white blood cells.
There are enzymes that degrade DNA, lipids and proteins.
|
ATTACHMENT SYSTEMS: Since many of the
nonspecific defenses involve mechanically flushing away pathogens, a common virulence
determinant of pathogens are cell components that stick the bacteria to the target cells.
Like the #attachment or docking proteins of viruses,
these systems stick things to one another. Two general attachment-systems have been found.
The pili are short protein rods or curled protein strands that have binding proteins on
the ends that attach firmly to receptor molecules on the surface of other (host) cells.
The other system is that of the capsule. #Capsules, as
you recall, are composed of sugar polymers (occasionally of protein polymers) that tend to
be sticky. These capsules are often produced in large quantities which entrap microbes in
sticky masses. For example, the plaque on our teeth is generally composed of a group of
microbes acting symbiotically together, through the production of pili and capsules, to
stick (like super-glue) to our teeth, gums and tongue. Figure 2 illustrates the action of
attachment systems which include pili, capsules and cell wall proteins.
SELF
DESTRUCTION: Pathogens frequently cause disease by tricking the host cells
into doing something they normally wouldn't do. One trick is to induce the host system to
produce self-destructive chemicals that kill
or inhibit its own cells. In doing this the body's own defense system is redirected
towards its own destruction, leaving the invading pathogen to enjoy the delicious and
nutritious remains. In fact many of the "diseases" caused by both viruses and
bacteria are the result of the pathogen "throwing a chemical monkey wrench" into
the finely turned and balanced machinery of the host's body. Pathogens do this by
producing chemicals that mimic host's regulatory chemicals. These "FAKE" substances bind to the host's cell
receptors, or regulatory sites, causing them
to turn on or off at inappropriate times. By disrupting the normal processes of the host,
the pathogen may escape destruction or detection; like a crook trying to escape the police
who are advancing on him by yelling "fire" in a crowd.
CHANGING ANTIGENS: Pathogens often
evade a host's immune system by frequently changing its surface antigens. The HIV, malaria
and sleeping sickness pathogens use this strategy to avoid destruction. In these cases a
pathogen produces a few antigenic variants as its population increases. Meanwhile the host
responds by making antibodies only against the major antigenic form. However, the
variant(s) survives, thrives and increases in number, while continuing to harm the host.
The host will then mount a second vigorous antibody attack against the new variant only to
have another new variant escape.
Eventually, the pathogen does so much damage that the weakened host is destroyed. In
effect the host's immune system is in a race with the pathogen's antigenic variation
system; the winner gets to live.
CAMOUFLAGE: In this case the
pathogen camouflages itself so the host doesn't recognize the invader as being
"nonself" and thus dangerous. One trick is to coat itself with a capsule which
the white blood cells either doesn't recognize or for some other reason avoids ingesting
(a YUCK capsule), thus allowing the capsule-covered pathogen to remain free and
unhindered. In other cases the pathogen may enter and hide within host cells, thus
escaping the patrolling white blood cell guards and their antibody guard dogs. Some
pathogens have even developed ways of moving or tunneling from one host cell to another
without coming out of the cell so they avoid detection by the defending immune system.
For convenience, the disease process is discussed in a series of sequential stages:
INFECTION = The pathogen
establishes itself in or on the host. It overcomes or avoids the nonspecific defenses and
gains a "foothold" which allows it to grow and reproduce. No symptoms are yet
present and the host is unaware of the infection. However, with newer molecular biology
methods (#PCR), we may soon be able to detect the presence
of a pathogen at this early stage when it is more vulnerable. In many cases the host
mounts a successful counter attack once the infection gets large enough for the host to
detect it. For example, this is the case with ZITS.
INCUBATION PERIOD = This is the period of
time it takes for the pathogen to establish itself to the point where the first disease
symptoms appear. This varies widely, for most bacteria it takes 2 to five days, but for
some like T.B. or leprosy it may be 20 to 30 years. For many viruses it is 3 days to two
weeks, but for rabies it may take several weeks or even months, whereas AIDS may take up
to 10 yr. to clinically develop if left untreated and with treatment it may take much
longer.
INITIAL SYMPTOMS = These refer to the first symptoms
that clearly demonstrate an illness. Since symptoms vary widely between hosts this is a
statistical matter. One person may have a subclinical case, where they feel mildly ill,
but with no clear symptoms, to others that show unusual symptoms that can be mistaken for
other diseases. Subclinical cases (asymtomatic cases) are very
common as indicated by the large number of people who have antibodies against
various diseases, but who have never been clinically diagnosed as having had a given
disease.
ACUTE = This refers to the
classical clinical or textbook symptoms, where the disease is in full flower and the patient is usually seriously or
clearly ill.
The intensity of the illness varies with the disease, the strain of the etiological agent and the condition of the patient. Some diseases like chickenpox and the "common cold" are almost always relatively mild and without complications. Others, like bubonic plague or measles are usually severe and life-threatening. Some, like rabies, Ebola and AIDS are close to being 100% fatal. In general, every infectious disease is survivable and every infectious disease can prove fatal to some people.
- The GENETICS of the host.
- The GENETICS infectious agent; virulent determinants, virulence plasmids etc.
- The PHYSICAL CONDITION of the host.
- The STRESS encountered by the host during the disease.
- The AGE & SEX of the host.
- The TREATMENT of the victim.
The complex interplay of these factors makes it difficult to predict the outcome of a disease of any given individual. Disease data is ENTIRELY STATISTICAL, like a horse race or the lottery.
RECOVERY = Period during which
the symptoms decline and the patient recovers. Recovery may take many paths. Six
major ones are listed below.
As discussed in Chapter XIII, most of us are born with an efficient defense system, designed over millions of years by evolution to protect us from infectious disease. We can not change our heredity, but we can learn how to work with it to protect ourselves from disease. We are like a finely tuned racing car which will go the distance if run correctly. However, if we make choices that damage the mechanics of our bodies, or of the car, we can significantly shorten the lives of both and harm the efficiency of their running. Wise choices, based on a knowledge of how things work will not guarantee that harm will not come to you or the car, for the car may be destroyed in a random collision or you may contract a fatal disease through a paper cut or a stray cosmic ray, but it will increase the favorable odds. No degree of understanding about the mechanism of disease or immunity is capable of overcoming poor decisions regarding health habits and lifestyle.
Click here to see an introduction to a large list of bacterial infections. View individual pathogen by visiting the various Volumes.
http://www.bact.wisc.edu/Bact303/Bact303pathogenesis; Excellent discussion on pathogens and pathogenic mechanisms.
Over 450 pictures of Parasites: Lot more frightening than any horror movie you'll ever see.
http://www-medlib.med.utah.edu/WebPath/INFEHTML/INFECIDX.html ; Lots of pictures of diseases, most are gross.
http://129.109.136.65/microbook/ch007.htm; Excellent discussion, with cartoons, on bacterial pathogenesis.
Copyright © Dr. R. E. Hurlbert, 1999.
This material may be used for educational purposes only and may not be duplicated for
commercial purposes.
SCIENCE HALL, ROOM 440CA
PHONE: 509-335-5108
FAX: 509-335-1907
E-MAIL: hurlbert@wsu.edu or hurlbert@pullman.com
Return to Table of Contents
