The Basics: Introduction to Microbiology and Infectious Disease

Like most fields, microbiology is one filled with jargon. Many laymen don't even realize the differences between a bacterium and a virus, much less the smaller differences between, for example, a pathogenic versus a commensal organism. So, while I haven't decided yet exactly what I might write about in future posts, I thought I'd begin with a very general microbiology primer to get everyone up to speed on the basics of the microbial word.

To begin with, in the "well, duh" category, microbiology is the study of very tiny life. Initially, those studied were mainly disease-causing organisms; pioneers such as Robert Koch and Louis Pasteur studied bacteria including anthrax and tuberculosis, developing the germ theory of disease and laying down postulates to decide whether a particular microbe is truly the cause of a specific illness along the way. And though this is obviously my focus as an infectious disease epidemiologist--looking mainly at microbes that cause disease (or at least have the potential to do so)--in one of the comments, it was noted that microbiology is about much more than just disease-causing organisms. I agree with that, and I'll try to do something on microbial ecology (though potentially with some kind of human disease angle thrown in there) in the future.

Generally today, the all-encompassing group of "microbes" are divided into viruses, bacteria, fungi, and protozoans. I will discuss each category briefly, and touch on prion diseases as well, finishing up with a brief introduction to our body's disease-control mechanism, the immune system. Please do keep in mind that the statements below are gross generalizations; exceptions exist to many of the basic guidelines put forth below. So to begin this veritable stew of information:

The Broth: Viruses

Viruses are the simplest organisms we are aware of. They are essentially nucleic acid (viruses can have genomes consisting of either DNA or RNA) wrapped in a protein coat.
On their own, viruses are incapable of any metabolism, including replication. However, viruses contain proteins on their surface which facilitate binding to and entry into cells of every type imaginable, from bacteria to human cells. Once inside, the viruses use the cell's machinery to churn out more copies of the viral genomes and produce virus-specific proteins. They then assemble into mature virions (virus particles) and leave the cell, either by causing lysis (breaking apart) of the host cell or by "budding" off it, taking portions of the host's cell membrane with it. A single cell may produce anywhere from 10,000 to 50,000 new viruses in as little as 48 hours' time.

Diseases caused by viruses include influenza (pictured above), the common cold, herpes, Ebola, and AIDS.

Add Some Carrots: Bacteria

Bacteria are single-celled organisms which populate almost every niche on earth, from the hottest springs and chilliest waters to many spaces on and within the human body. As a group they are extremely diverse in size, shape, motility, nutrient requirements and pathogenicity (ability to cause disease), but share the common trait of lacking a true nucleus (and hence are referred to as "prokaryotic").

Though most of the earliest bacteria discovered were pathogens (disease-causing organisms), the vast majority of bacteria on earth are harmless, or even helpful, to humans. Many animals rely on gut bacteria to provide nutrients from food, which we are unable to synthesize ourselves (for example, E. coli in the gut produce Vitamin K). Additionally, commensal (non-pathogenic) bacteria fill niches in our body and use resources that would otherwise be available to other pathogenic microorganisms. For instance, our skin and oral cavity are covered with bacteria, most of which will never harm us, as they live in a delicate balance with our immune system.

Diseases caused by bacteria include tuberculosis (Mycobacterium tuberculosis), "Black Plague," (Yersinia pestis), strep throat (Streptococcus pyogenes), and syphilis (Treponema pallidum - pictured right).

Mmmm, protozoans

Protozoans are single-celled, eukaryotic organisms belonging to the kingdom Protista. This means that, like human cells, they have a true nucleus. Most protozoa are motile as well, and are often fairly large for a single-celled organism (generally 1-100 microns in size, although some can be up to 1 millimeter in length). Most produce asexually as bacteria do, but like bacteria, they can exchange genetic material "sexually" via conjugation. Of the ~50,000 or so known species of Protists, only a handful are responsible for disease in humans. However, those that are pathogens are responsible for some of mankind's nastiest, and most numerous, ailments.

Diseases caused by protozoa include: malaria (Plasmodium falciparum - pictured left), sleeping sickness (Trypanosoma cruzi), amoebic dysentery (Entamoeba histolytica).

Maybe a Few Mushrooms: Fungi

Fungi are also eukaryotic, and include organisms such as molds and yeasts. Approximately 100 fungal species (out of ~100,000 known) are pathogenic for man. Yeasts are superficially similar to bacteria, in that they are unicellular and generally divide by simple binary fission (one cell divides into two). Molds, on the other hand, generally have complex life cycles during which they pass through both an asexual and a sexual stage. They exist as multicellular organisms during much of this period, and at this point, are far from being "micro" organisms. Nevertheless, because it is often their (microscopic) spores which are responsible for diseases, they remain classed as general "microbes."

Diseases caused by fungi include thrush and yeast infections (Candida albicans - click here for picture of candida and thrush in babies), and ringworm/athlete's foot (various species).

Disease due to fungi can also be caused by contact with or ingestion of toxins produced by certain species. For example, aflatoxin is a poison produced by the mold Aspergillus flavus (whose complex life cycle is depicted to the left). When ingested, symptoms may include vomiting, convulsions or death.

Don't Forget the Beef: Prions

I will take a moment here to mention prions, as they are classified as infectious agents as well ("prion" is derived from Proteinaceous infectious particle.) However, prions are unique in that they contain no genetic material--the infectious agent is a protein alone. How, then, do they cause disease? Do they replicate? Well, no, not exactly. Prions are a misfolded form of a normal host protein. When the misfolded form is present along with the normal isomer, the misfolded prion causes the normal protein to misfold as well. As such, the presence of a small amount of prion can cause a great deal of damage due to this amplification effect. This damage can lead to actual holes in the brain tissue (such as those shown in the bottom panel, below right), and as such, several of the diseases caused by prions are termed "spongiform encephalopathies." In humans, prion diseases can be due to genetic mutations or due to ingestion of or contact with material contaminated with prions.

Human prion diseases include kuru, Creutzfeld-Jacob Disease (CJD), and Familial Fatal Insomnia (FFI).

Stir it up: novel infectious agents

Though this covers the main groups of what we typically consider to be "microbes," the possibility certainly remains that there are other organisms that remain to be discovered. Additionally, organisms we're familiar with can also be transmitted and cause disease in unique ways. For example, Stickler's sarcoma, a cancer of dogs, has recently been found to be due to the direct transmision of tumor cells from dog to dog. A similar condition was identified recently in Tasmanian devils. These eukaryotic cells act as a unique species and are spread like other infectious agents, but are mammalian in origin--so how do we classify them? And how many other currently unknown organisms may be out there?

Season to Taste: A Touch of Immunology

No discussion of microbiology as it pertains to infectious disease is complete without a brief mention of the immune system. Why is this? Our immune system is the main line of defense against attacking microorganisms, and a main force driving the evolution of microbes we're in contact with (as well as vice-versa; microbes have been a force in human evolution as well). When our immune defenses are down, we are vulnerable to being overwhelmed by even commensal organisms, which are usually held in check by our body's natural defenses. This is why a disease such as AIDS is so deadly: by destroying one aspect of the body's immune response, it leaves the host susceptible to a plethora of infections.

Additionally, many of the symptoms of an infectious disease are due to responses of the immune system. Fever, for example, is due to the production of proteins called cytokines in response to an infectious agent. Cytokines serve to dilate the blood vessels, allowing blood cells to seep out of the capillaries and into the tissue. This causes the typical red flush of a fever. Fluid also is released from the vessels, causing swelling; and proteins called pyrogens ("fever-producers") act on the brain to increase the body's rate of metabolism, raising its temperature to one incompatible with the growth of many pathogenic agents. Thus, while we see fever as a symptom, it is actually a carefully controlled evolutionary response to dealing with infectious agents.

The real workhorses of the immune system, however, are the cells collectively referred to as white blood cells. The primary defense is provided by a group of cells termed phagocytes ("eater cell"). Their job is to engulf and destroy debris, which includes foreign organisms and proteins. The other key warriors of our immune system are the B and T lymphocytes. These cells are critical to immune function. B cells produce and release proteins called antibodies, which circulate in the blood, recognizing and bind to invading pathogens, targeting them for destruction and elimination. T cells, on the other hand, recognize host cells that are expressing abnormal proteins; this includes cells infected by viruses or other foreign agents. They then target these cells for killing by phagocytes or other mechanisms. As a general rule, B cells (and the antibodies they produce) are most important when dealing with bacterial, protozoa or fungal infections; T cells, on the other hand, are most important when fighting a viral infection.

Finally, while the immune system is critically important in fighting disease, it is important to take into consideration simple physical barriers as well. The first and most important is the skin; when unbreached, it provides an excellent first line of defense against offending microorganisms. A second line of defense is the mucus layer, which coats most of our internal epithelium (the layer of cells covering all surfaces of the body). This works both to physically trap microorganisms, as well as to kill them due to the presence of antimicrobial substances in the mucus. Other barriers include the acidity of the stomach, which kills greater than 99% of all organisms ingested; and ciliated cells (a type of cells which contain a specialized flagellum) which line our lungs, to aid in expelling microorganisms from the body. Finally, as mentioned above, commensal organisms cover many spaces on and within our body, using nutrients and taking physical space away from any potential harmful invaders.

Additional Courses...

The above is meant to serve simply as a very basic introduction to a gargantuan field of research. A reason I find this subject so interesting is because it truly is one that affects all of us. Microbes are impossible to avoid, and we all are in contact with literally hundreds of millions of them as we go through our routines each and every day. Therefore, it behooves us all to know at least a bit about them, in order to avoid unwittingly creating a recipe for disaster.

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Nicely done, Tara. Brief and to the point, but also eminently understandable.

A very nice primer. You definitely have a gift for communicating the relatively specialized focus of your field to laymen like me. I look forward to the rest of this series.

viruses as "organisms"?
(p.s. you need to close an italics tag)

I like to think of prions as "infectious poisons".
You also left out "virioids" (e.g. Coconut Cadang-Cadang disease) but I think those are even more obscure than prions and as far as I know only affect plants...

This is great! I couldn't resist taking notes, though I don't know what to do with them now.

Generally today, the all-encompassing group of "microbes" are divided into viruses, bacteria, fungi, and protozoans.
What about archaea? I know they don't cause disease but they are microbes.

Stickler's Sarcoma and Devil Facial Tumor Syndrome don't really belong, since they are multicellular parasitical organisms. Albeit descended from another phylum entirely. While both are closely related to dogs and tasmanian devils respectively, there has been radical genomic alteration. Especially in Stickler's Sarcoma, where last I heard as much as 50% of the genome has been lost.

Learning how Stickler's Sarcoma specimens adapt to their host could fuel many a doctoral thesis.

Stickler's Sarcoma and Devil Facial Tumor Syndrome don't really belong, since they are multicellular parasitical organisms. Albeit descended from another phylum entirely.

Well, but many bacteria as well go into a multicellular form during infection--any infection that involves the formation of a biofilm, for example. From what I understand, Stickler's sarcoma and the Tasmanian devil cancer are transmitted quite like an "ordinary" infectious disease; the infecting agent is just much different than what we usually think of.

Neophye question. Given fever as defence, why do we try to reduce a fever? Is the fever dangerous in and of itself or just a symptom?

Really interesting reading, Tara. Thank you.

A bit late on the response but a fever is intended to be helpful, but like many things, it can go out of control.

In terms of viruses such as the common cold, it has been shown that without any intervention such as fever reduction and cough suppressants one tends to recuperate from it faster than otherwise. Although they will be more uncomfortable for that time period. The optimal temperature is 2 degrees above normal for many animals and ones body tends to try to enforce this difference by heating up when the ambient temperature is cooler and trying to cool off when it is warmer. Cold blooded animals have been shown to find areas that match the 2 degree difference as well and will move out of the area if it becomes too warm. I am unsure of the exact mechanics but I have heard several places that in some viruses the temperature difference stops them from being able to acquire iron from the host bodies cells.

I am sorry I do not have any references for you but
is probably a good starting point.