Community College of Indiana

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Host - Microbe Interactions

I. The term symbiosis refers to two organisms of different speices living together.  This close interaction between organisms can be of benefit to both organisms, benefit one organism with no negative affect on the other, or can benefit one and adversely affect  the other.

A.  Mutualism refers to those interactions that benefit both organisms.  The normal flora of our gut live in symbiosis with us.  We benefit form their production of certain vitamins while they benefit from our provision of food and shelter.

B.  Commensalism refers to relationships that benefit one organism with no good or bad effect for the other.

C.   Parasitism refers to relationships in which one organism benefits at the other expense.  Humans are stricken with a range of parasitic worms.  Viruses and pathogens are usually considered parasitic organisms.

II. The body harbors large numbers of bacteria that exist in a mutualistic or commensulistic relationship with the host.  These organisms are referred to as the resident flora, indigenous flora or, more commonly, the normal flora. When a baby is born it lacks any normal flora.  Passing through the birth canal and during the first weeks of life it is exposed to bacteria and fungi that will invade and colonize most exposed surfaces of the skin, the mucus membranes of the GI tract and portions of urinary tract and respiratory tract. 

A.  The epidermis harbors extensive numbers of bacteria belonging to the genera of Staphylococcus, Micrococcus and Corynebacterium and Propionibacterium.  These organisms invade the upper layers of the stratum corneum (cornified layer of the epidermis) and the glands of the skin (sweat glands and sebaceous glands), they do not colonize the underlying dermal layers.    Contamination of the outer most layers of the skin regularly occurs.  Contaminating organisms can include viruses, bacteria and fungi but they usually do not colonize and are usually easily removed.  These are referred to as the transient populations. 

B.  The alimentary canal harbors large numbers of bacteria.  The oral cavity has specific types of organisms that are most commonly found in the mouth.  Once again only the epithelial layer is colonized.  Underlying connective tissues remain sterile. 

1.  The bacteria that inhabit the colon survive upon the undigested material that passes through the small intestine.  These bacteria metabolize these “undigested wastes”.  The action of these organism results in the production of the chemicals that give feces its distinctive odor and produce the gas that results in flatulence.

2.  Production of certain vitamins by the bacteria that the host can not synthesize is a great benefit to the host. 

3.  Disruption of the normal flora of the gut by the use of broad spectrum antibiotics can result in the overgrowth of certain species normally found in low numbers in the gut.  This can result in problems such as diarrhea or inflammation of the gut mucosa.   

C.  The outer portion of the male and female urethra is colonized by several types of organisms.  Spread of these organisms beyond the distal portion of the urethra is not normal and often is the precursor to disease. 

D.  Resident populations growing on our skin or mucus membranes use the available nutrients, produce metabolites and sometimes produce substances that have a direct antibiotic affect.  Collectively this inhibits other organisms (which might be disease causing) from establishing populations on these sites of our body. When one organism’s growth interferes with the colonization and growth of another organism it is referred to as microbial antagonism. 

II. Most of the bacteria found in or on the human body cause no disease if they are in the proper place and in the proper number. But certain microorganisms do cause disease when introduced into an otherwise healthy individual. These organisms are referred to as the true pathogens. By overcoming the defenses of a normal healthy host, true pathogens colonize and cause disease within that host. Many organisms cause disease only in a weakened host, a host with disrupted normal flora or if they have been allowed entry to a site where that bacteria is not usually found. This type of pathogen is referred to as an opportunistic pathogen. If the pathogen responsible for a disease can be spread from one host to another, the disease is said to be communicable. Most of the diseases that we will talk about in this course are communicable. Noncommunicable diseases are either inherited, the result of ingestion of toxins or caused by normal flora introduced into the wrong environment. (ex. Puncture of the bowel introduces E. coli into the peritoneal cavity.) Communicable diseases that are easily spread are said to be contagious. The combination of common symptoms and signs that are strongly related to a particular disease are referred to as a syndrome.  

A. The biochemical characteristics that influence the severity of disease that a particular organism causes are referred to as virulence factors. Often times virulence factors involve production of proteins that allow for adherence to certain surfaces, aid in evading or destroying cells of the body's defenses or are secreted toxins.

B. For an organism to cause disease it must gain entry to particular sites. The route by which an organism gains entry is referred to as the portal of entry.  If the organism is acquired from the environment or from contact with another host, the spread is said to be exogenous. Transfer of normal flora from its appropriate site to a site where it will cause disease is referred to as endogenous spread.

C. Though certain organisms can colonize the glands of the skin resulting in inflammation and eventually disease, in most cases, introduction of organisms onto a healthy skin surface results in little or no pathology. If the skin has been cut, abraded, burned or otherwise disrupted, it is susceptible to infection.

D. The gastrointestinal (GI) tract is particularly susceptible to colonization by a wide range of pathogens which usually gain entry to the gut when food or water contaminated with feces is ingested. The pathogens will be shed in the feces. This is referred to as the oral-fecal route of transmission. Often these pathogens produce toxins that result in diarrhea or bleeding into the gut. Recently the role of bacteria in certain types of ulcers (gastric and duodenal ulcers) has been demonstrated.  Often inanimate objects contaminated with microscopic amounts of feces can serve as a vehicle for the transmission of a pathogen.  Such inanimate objects are referred to as  fomites (fomites can play a role in the transmission of respiratory and sexually transmitted pathogens as well).

E. Colonization of the pharynx, trachea, bronchi and pleura is not uncommon. In many, if not most, cases the pathogens are inhaled. Once infection is established, the organisms leave the host when secretions of the respiratory tract are aerosolized during sneezing or coughing. The droplets that are produced carry the organism. In some cases the pathogen can survive the dehydration of this droplet. The remaining dried mucus is referred to as a droplet nuclei. Organisms that can be transmitted via droplet nuclei usually are more easily spread. This route of transmission is often referred to as aerosol transmission.

1. Pneumonia refers to inflammation of the lungs which results in the collection of fluid in the air spaces. Often this inflammation is caused by a pathogen (bacterial, viral or fungal).
2. If the agent invades the lining of the lung (the pleura) it results in pleuritis. Often initial infection of the respiratory tract with viral agents can result in an opportunistic infection by bacteria that are part of the normal flora of the upper respiratory tract. 

F. Infection of the reproductive tracts and the male urinary tract often is the result of sexual activity. Sexually transmitted diseases (STD's) involve pathogens that colonize the reproductive organs and/or shed in the body fluids secreted during intercourse. Condoms can reduce the risk of transmission of most STD's but they do not eliminate the risk.

G. Infection of the fetus by transplacental transmission of pathogens is rare. Most pathogens lack the ability to cross the placenta and thus do not invade the fetus. Those organisms that can cross the placenta will do considerable damage to the fetus due to the lack of a fully functioning immune system in the fetus. Cytomegalovirus which causes little or no disease in the healthy adult does considerable damage to the fetus.   Rupture of the fetal membranes can lead to infection of the fetus by not only normal flora of the vagina but also any pathogens that are present in the vagina or it's secretions.   

1. As the fetus passes through the birth canal, it will be inoculated with those organisms present on the mucous membrane of the vagina and those organisms present in the secretions of the vaginal.  Women infected with gonococcus,  herpes simplex virus and other STD's will  infected  to the neonate as it is delivered.
2. Because of the immature state of the immune system in the newborn and the lack of resident populations of bacteria, it is susceptible to many opportunistic infections.  

H.  Many pathogenic organisms require transfer of body fluids. This may involve sexual contact, sharing contaminated needles or surgical equipment, blood transfusions or bug bites.

1. The pathogens that cause sexual transmitted diseases (STD's)  are found on the mucous membrane of the reproductive tract or shed in the semen or vagina secretions.   These organisms usually are transmitted during the sex act as body fluids are exchanged.

2.  Parenteral transmission involves introduction of the pathogen into the tissues, blood stream or internal body cavities usually by way of injection.  Sharing of needles often leads to parenteral transmission.     

I. Disease agents are maintained in the environment in what is referred to as reservoirs.

1. Some pathogens continue their existence by constantly moving from one infected host to another. Often this results in endemic occurrence of the disease in a population. An example of this is the common cold. Other pathogens establish carrier states in which the host shows no apparent signs of illness but continues to shed the organism and infect those around them. Typhoid fever is a good example of this.
2. Certain diseases are maintained in animals and only occasionally infect humans. Such diseases are referred to as zoonotic diseases. Rabies virus is a good example of an agent disease that infects humans but usually only infects animals (skunks in this part of the country).
3. Non-living reservoirs can include soil, water and food. In the case of water, contamination by sewage or animal wastes can introduce parasitic worms or bacteria that infect the gut. When contaminated water is used for cleaning, processing, or growing food the contaminating organism can be transferred.

III. Factors that influence virulence include the volume of the inoculum, the proteins that the pathogen displays for adherence and the proteins that the pathogen releases into the host.

A. For most pathogens the infectious dose (ID) is the minimum number of organisms or virus particles needed to cause disease. For some diseases as few as one agent is all that is needed but for most pathogens 100-10,000 microbes must be introduced into the body for disease to be probable.

B. Proteins that allow the bacteria to adhere to the surface of certain tissues also play a significant role in the development of disease. Lack of these proteins precludes colonization and thus disease.

1. The capsule and fimbriae are most important in attachment. It should be noted that the capsule also plays a role in the evasion of phagocytic cells such as macrophages.
2. A viruses ability to spread from the initial site of infection to other sites within the body is limited by that viruses ability to attach to possible target cells.   Those viruses with the capacity to infect a wide range of cells will often create a much more severe infection.

C. Release of proteins into the surrounding environment can cause several things to occur.

1. Exoenzymes often destroy proteins or other chemicals designed to kill or limit the spread of the pathogen.

a. Mucinase is release by several pathogens that cause intestinal diseases. This protein destroys the protective layer of mucus on the intestine wall and thus allows access to the underlying epithelial tissue.
b. Keratinase destroys the protein keratin which is found within cornified epidermal cells. By destroying keratin in epidermal cells, the pathogen can gain entry into the deeper layers of the epidermis.
c. Collagenase destroys collagen. This is the main protein of most connective tissues. Once the collagen has been digested the pathogen can spread much more readily.
d. Hyaluronidase dissolves the protein that cements cells together in many tissues. Organisms that secrete this protein can then bypass the barrier normally presented by these tissues. This allows the bacteria to more rapidly gain access to the circulatory system.

2. Endotoxins are a component of the gram negative cell wall. They are released when a cell dies and begins to undergo autolysis. Endotoxins are the lipopolysaccharide found in the outer membrane of gram negative cell walls.

3. Toxins which are produced and then released from the bacterial cell are referred to as exotoxins. Bacteria that can synthesize and release a toxin are said to be toxogenic. Often bacteria infections will be accompanied by the release of toxins into the blood stream; this is referred to as a toxemia. If the bacteria produced the toxin outside the body (while growing in food) and then the toxin was ingested the condition is referred to as an intoxication. In most cases exotoxins are proteins.

a. Exotoxins that affect the kidneys are referred to as nephrotoxins. Those that exert their effect on the mucous membrane of the digestive tract are referred to as enterotoxins.
b. Those that result in the rupture of white blood cells and red blood cells are referred to as leukotoxins and hemotoxins (or hemolysins), respectively.

D. Many of the proteins mentioned above assist the bacteria in evading the body's defenses. Along with these proteins the presence of a capsule plays a big role in determining the pathogenicity of a microbe. The capsule appears to allow for adherence to certain sites and to make the bacteria a poor target for phagocytosis. Phagocytosis by a neutrophil or macrophage is a crucial first step in the recruitment of other white blood cells and in the development of immunity.

IV. Within a single host a disease will "run a particular course". This is reflected in the severity and duration of clinical signs and symptoms and involves several distinct phases of infection:

A. Upon initial exposure to a pathogen there is a period in which no signs or symptoms are present. This is referred to as the incubation period. During this period the pathogen is increasing in numbers within the body and often spreading to other sites in body. The prodomal period follows in which the patient begins to feel sick but signs and symptoms are mild. The period of invasion or acute phase of infection is the time when pathogens are at their highest level within the body and signs and symptoms are most acute. If the patient is to recover, a convalescent period follows. Depending on the pathogen, the patient will be able to transmit the pathogen to others at certain stages of the disease's progression. Some pathogens are released in high numbers only during the prodomal period; most are released in greatest numbers during the period of invasion. Some are released at all stages and long after the disease state has resolved.

1. Acute diseases usually develop quickly and are resolved quickly.
2. Diseases that do not resolve, resolve incompletely or reoccur are said to be chronic. Usually these diseases to not develop quickly.
3. Subacute diseases never cause severe clinical signs. If they   produce so little pathology that the host is unaware of infection, they are said to be subclinical.
4. Latent infections may result from a clinical or subclinical infection. The disease agent is carried by the host for long periods of time without the host showing any clinical signs. Depending on the pathogen, the host may be infectious during this long period or not. In some cases, the infectivity of the host waxes and wanes.

5. Some pathogens will create pathological changes of sites other than those sites initially infected long after the resolution of the initial infection.  Such a pathological change is referred to as a sequela of infection.

B. Symptoms are those effects of a disease that the patient describes. Those changes in body function that can be observed or measured are referred to as clinical signs. Consequently, a pediatrician working with a 1 year old, technically is working only with signs and has no symptoms.

C. Within the host, the etiologic agent of a disease can demonstrate several different types of distribution and different extents of pathology.

1. When the infection is limited in its spread throughout the body the infection is said to be local. Puncture wounds and lacerations often introduce local infections. Skin lesions such as athlete's foot or boils are also examples of local infections.
2. Systemic infections result from the spread of the agent throughout the body. Often this involves movement of organisms or toxins by way of the blood or lymph. If a toxin produced by a local infection is spread by the blood it is referred to as toxemia. When organisms are distributed by the blood it is referred to as a bacteremia. If the organisms actually multiply in the blood it is a septicemia.
3. Infections caused by opportunistic pathogens in patients with immune systems that are not fully functional due to an acute primary infection result in what is referred to as a secondary infection. In the case of elderly or patients with poorly functioning immune systems secondary infections create considerable problems.

Want to know more?  Here are some good links!

Medical Microbiology Textbook   Normal Flora  http://gsbs.utmb.edu/microbook/ch006.htm

Medical Microbiology Textbook   University of Texas

University of Connecticut  Fundamentals of Microbiology, 

Mechanisms of Pathogenesis
        http://www.sp.uconn.edu/~terry/229sp98/pathogens.html

 

Send E-Mail to the Course Coordinator  (Todd Murphy)

Microbiology Homepage

Schedule for Summer 2004

Ivy Tech State College, Central Indiana