Prokaryotes Consist of Millions of Genetically Distinct

¶ … prokaryotes consist of millions of genetically distinct unicellular organisms. A procaryotic cell has five essential structural components: a genome (DNA), ribosomes, cell membrane, cell wall, and some sort of surface layer which may or may not be an inherent part of the wall (1). Functional aspects of procaryotic cells are related directly to the structure and organization of the macromolecules in their cell make-up, i.e., DNA, RNA, phospholipids, proteins and polysaccharides. Diversity within the primary structure of these molecules accounts for the diversity that exists among procaryotes (1). Identifiable groups of prokaryotes are assembled based on easily observed phenotypic characteristics such as Gram stain, morphology (rods, cocci, etc.), motility, structural features (e.g. spores, filaments, sheaths, appendages, etc.), and on distinguishing physiological features (e.g. anoxygenic photosynthesis, anaerobiasis, methanogenesis, lithotrophy, etc.). Prokaryotes are commonly known as bacteria, and it is estimated that bacteria have been around for at least 3.5 billion years

Different families of bacteria have different shapes. Typical cell shapes are straight rods (bacilli), spheres (cocci), bent or curved rods (vibrios), spirals (spirochetes), or thin filaments. Some bacteria exist as single cells, while others form clusters of various shape and complexity. Many groups of bacteria have a cell wall, which is mostly comprised of peptidoglycan (a chemical composed of carbohydrates and proteins). Gram-positive organisms have a relatively thick layer of peptidoglycan and stain violet when applied with certain dyes; gram-negative organisms have a thin layer of peptidoglycan covered by an outer membrane and stain red under the same application of dyes. Thus, Gram staining is an important method for identifying bacteria (5). However, the most precise method of classification is genetic analysis (5). Each species of bacteria has a unique genetic makeup, and a unique sequence of deoxyribonucleic acid (DNA) bases.

Many bacteria have structures and processes that allow them to adapt to hostile environments, and they can exist under a range of conditions. Those that require oxygen for growth are called obligate aerobes. In contrast, obligate anaerobes will not grow in the presence of oxygen. Acidophiles are bacteria that grow optimally under acidic conditions (pH of less than 7.0), while alkaphiles prefer alkaline or basic conditions (pH of greater than 7.0). Organisms that require a temperature near 99°F (37°C) (the body temperature of warm-blooded animals) for growth are called mesophiles; those that grow at temperatures above 113°F (45°C) are called thermophiles; and psychrophiles are able to grow at temperatures near 32°F (0°C). Halophiles require sodium chloride (salt) for growth; osmophiles are able to grow in environments high in sugar; and xerophiles grow under dry conditions (1).

Bacteria grow and replicate in a process known as binary fission. In this process, a parent cell divides to produce two daughter cells. The process begins with the growth of the parent cell; the chromosome unwinds and replicates, each copy moving to opposite ends of the cell. The cell is then partitioned in half by the production of a dividing wall (called the septum). The cell is cleaved at the septum, and two daughter cells are produced. If necessary nutrients and energy sources are present, the daughter cells then go on to reproduce as parent cells. The dynamics of a population of bacteria change during binary fission. The doubling time, or time required for one parent cell to produce two daughter cells, varies by bacteria species and strain and also by the environmental conditions. All bacteria exhibit a characteristic pattern of growth when introduced to a new medium; this is known as the growth curve (1).

PATHOGENIC BACTERIA

Only a small percentage of the vast population of bacteria is pathogenic (disease-causing) to humans. Many species of bacteria colonize the human body and are called the normal flora. Organisms of the normal flora are normally found on surface tissues such as skin, mucous membranes, and the gastrointestinal system. It is when bacteria enter normally sterile areas of the body, such as the brain, blood, and muscle tissue that disease may result. Some organisms of the normal flora neither harm nor provide benefit to the human body; this relationship is called commensalism. Normal commensals are bacteria that can always be found on or in healthy individuals and rarely cause disease. Bacteria that occasionally colonize the human body without causing disease are called occasional commensals. Although a human fetus is sterile in utero, colonization with normal flora bacteria begins with birth when the baby comes into contact with the mother's vaginal bacteria, and continues with breast feeding and subsequent contact with the environment.

Many other types of bacteria interact with the human body in a relationship called mutualism, from which both organisms benefit (5). There are a number of ways that bacteria benefit the human host. Normal flora bacteria on the skin such as Staphylococcus epidermidis protect against colonization by pathogenic bacteria, through a process called microbial competition. Bacteria in the vagina (e.g., Lactobacillus acidophilus) help to establish an acidic environment that inhibits colonization of pathogenic bacteria and yeast. Another example of helpful bacteria is the normal flora in the gastrointestinal (GI) tract (e.g., Escherichia coli) which secrete vitamins such as K. And B12 that are essential for normal cellular function.

Although normal flora bacteria are not normally pathogenic, disease may result from invasion of normal flora into normally sterile areas of the human body, or if the host immune system is compromised. When bacteria that normally reside in the GI tract (such as E. coli) are introduced to the urinary tract, for example, a urinary-tract infection may result. This is considered an endogenous infection. Exogenous infections result from invasion of noncommensal organisms, which are bacteria not normally found in or on the human body. Transmission of exogenous bacteria may occur by various routes, including inhalation of aerosolized organisms, ingestion of contaminated food, or direct contact of a wound or mucous membrane with organisms. When bacteria first enter the body, local inflammation may be the first sign of infection. Physical symptoms such as pain, erythema (redness), edema (swelling), or pus formation result from the response of the immune system against the invading bacteria. If the bacteria spread to the bloodstream (bacteremia), they may disseminate to and colonize at various sites in the body.

Some of the most common bacteria that are pathogenic to humans include staphylococcus, streptococcus, neisseria, escherichia, salmonella, vibrio, clostridium, mycobacterium, and chlamydia. Staphylococci are gram-positive bacteria found as part of the normal flora of most individuals. S. aureus is the causative agent of many infections, including toxic shock syndrome (TSS), staphylococcal food poisoning, impetigo, and furuncles (boils). S. Saprophyticus causes urinary-tract infections in sexually active women. S. Epidermidis may infect damaged or artificial heart valves and cause a condition called endocarditis. Streptococci are gram-positive bacteria that commonly colonize the oropharynx (the area of the throat at the back of the mouth). Example syndromes include pharyngitis (sore throat), scarlet fever, necrotizing fasciitis (streptococci are popularly known as the "flesh-eating bacteria"), and rheumatic fever. S. Pneumoniae is a common cause of bacterial pneumonia and meningitis. Neisseria gonorrhoeae is the causative agent of gonorrhea, which is one of the leading sexually transmitted diseases (STD). N. Meningitidis is a leading cause of adult meningitis. Escherichia coli (E. coli) is one of the most commonly encountered bacterium. The bacteria is a common cause of gastroenteritis (inflammation of the lining of the stomach and intestines) but also causes urinary-tract infections and neonatal meningitis. Most Salmonella infections result from ingestion of contaminated food and lead to enteritis. Typhoid fever is also caused by salmonella bacteria, S. typhi. Cholera is caused by a Vibrio bacteria, V. cholerae, which is spread by ingestion of contaminated food or water. Cholera infection is an important cause of diarrheal disease in many developing countries. Clostridium is responsible for a number of human diseases. C. Perfringens causes a variety of human diseases, including myonecrosis (gas gangrene), clostridial food poisoning, and soft-tissue infections (cellulitis and fasciitis). Tetanus (also known as lockjaw) is caused by C. tetani; C. botulinum causes food-borne botulism. Tuberculosis caused by infection with Mycobacterium. tuberculosis, is a highly prevalent pulmonary disease. Hansen's disease (also known as leprosy) is caused by M. leprae. Chlamydiae, once thought to be viruses because of their small size, cause numerous human diseases. C. Trachomatis is the causative agent of conjunctivitis (inflammation of the outer surface of the eye), infant pneumonia, and urogenital chlamydia. Bronchitis, pneumonia, and sinusitis are often caused by C. pneumoniae.

VIRULENCE FACTORS

Bacteria have developed numerous mechanisms that allow them to invade a host and colonize an otherwise inhospitable site to cause disease. Many of these mechanisms enhance their ability to cause disease in humans; such traits are called virulence factors. Some common virulence factors include, bacterial growth, the release of toxins, capsule formation, granuloma formation, and antigenic mimicry. The byproducts of normal bacterial growth may cause tissue destruction if colonization has occurred in a normally sterile site. For example, Clostridium perfringens is a normal flora bacteria of the GI tract but may cause gas gangrene if it infects a wound or trauma site. Bacterial release of toxins is usually the result of protein production that is inevitably toxic to the host. Some bacteria are capable of forming a surrounding capsule that serves as a protective shield around a bacterium and help the cell to evade immune response. The formation of a granuloma is also a protective mechanism for bacterium. A granuloma is a lesion formed in response to infection by some intracellular pathogens. Viable bacteria are walled off in the granuloma and thus prevented from further colonization. In antigenic mimicry, a bacterial cell may be able to trick the immune system by presenting antigens (molecules recognized by antibodies) that are similar to host antigens. Immunological cells therefore have difficulty distinguishing between the bacterium and a host cell.

PUBLIC HEALTH AND ANTIBIOTIC RESISTANCE

When penicillin became widely available during the Second World War, it was a medical miracle. Discovered initially by a French medical student, Ernest Duchesne, in 1896, and then rediscovered by Scottish physician Alexander Fleming in 1928, the product of the soil mold Penicillium halted the progression of many types of disease-causing bacteria. But just four years after drug companies began mass-producing penicillin in 1943, microbes began appearing that could resist it (4). The first bug to battle penicillin was Staphylococcus aureus. This bacterium is often a harmless passenger in the human body, but it can cause illness, such as pneumonia or toxic shock syndrome, when it overgrows or produces a toxin.

In 1967, another type of penicillin-resistant pneumonia caused by Streptococcus pneumoniae and called pneumococcus, surfaced in a remote village in Papua New Guinea. At about the same time, American military personnel in Southeast Asia were acquiring penicillin-resistant gonorrhea from prostitutes. In 1983, a hospital-acquired intestinal infection caused by the bacterium Enterococcus faecium joined the list of bacterium that was resistant to penicillin.

Antibiotic resistance spreads fast. Between 1979 and 1987, for example, only 0.02% of pneumococcus strains infecting a large number of patients surveyed by the national Centers for Disease Control and Prevention were penicillin-resistant (3). Today, 6.6% of pneumococcus strains are resistant, according to a report in the June 15, 1994, Journal of the American Medical Association by Robert F. Breiman, M.D., and colleagues at CDC (2). The agency also reports that in 1992, 13,300 hospital patients died of bacterial infections that were resistant to antibiotic treatment.

New forms of bacteria have mutated into resistant strains that can counteract modern antibiotic drugs. The Centers for Disease Control in Atlanta, GA reports that organisms now exist that are resistant to every known antibiotic drug (3). The emergence of bacterial strains that are resistant to treatment by current antibiotics is an important public-health concern. Antibiotics are chemical substances produced by microorganisms that inhibit bacterial growth or kill bacterial cells. It is apparent that bacteria are mutating to become resistant to once effective antibiotics. Since antibiotics first became widely used in the World War II era, countless lives have been saved, and serious complications of many diseases and infections have been attenuated. However, after more than 50 years of widespread use, many antibiotics are exhibiting a diminished effect. Some bacteria have developed ways to resist the effects of antibiotics. Widespread use of antibiotics is thought to have spurred evolutionary changes in bacteria. Diseases such as tuberculosis, gonorrhea, malaria, and childhood ear infections are more difficult to treat today than they were decades ago. Drug resistance is an especially difficult problem for hospitals because they harbor critically ill patients who are more vulnerable to infections than the general population and therefore require more antibiotics. Heavy use of antibiotics in these patients increases bacterial mutations that bring about drug resistance (4).

Nearly two million patients in the United States get an infection in the hospital each year. Of those patients, about 90,000 die each year as a result of their infection-up from 13,300 patient deaths in 1992 (3). More than 70% of the bacteria that cause hospital-acquired infections are resistant to at least one of the drugs most commonly used to treat them.