Medical microbiology 6th ed p murray, k rosenthal, m pfaller (elsevier, 2009)

Table of contents
Section I Introduction
Section II Basic Principles of Medical Microbiology
Section III Basic Concepts in the Immune Response
Section IV General Principles of Laboratory Diagnosis
Section V Bacteriology
Section VI Virology
Section VII Mycology
Section VIII Parasitology
Section I
1 Introduction to Medical Microbiology.htm?
Section II
2 Bacterial Classification, Structure, and Replication.htm?
3 Bacterial Metabolism and Genetics.htm?
4 Viral Classification, Structure, and Replication.htm?
5 Fungal Classification, Structure, and Replication.htm?
6 Parasitic Classification, Structure, and Replication.htm?
7 Commensal and Pathogenic Microbial Flora in Humans.htm?
8 Sterilization, Disinfection, and Antisepsis.htm?
Section III
09 Elements of Host Protective Responses.htm?
10 Humoral Immune Responses.htm?
11 Cellular Immune Responses.htm?
12 Immune Responses to Infectious Agents.htm?
13 Antimicrobial Vaccines.htm?
Section IV
14 Microscopic Principles and Applications.htm?
15 In Vitro Culture Principles and Applications.htm?
16 Molecular Diagnosis.htm?
17 Serologic Diagnosis.htm?

Section V


18 Mechanisms of Bacterial Pathogenesis.htm?
19 Laboratory Diagnosis of Bacterial Diseases.htm?
20 Antibacterial Agents.htm?
21 Staphylococcus and Related Gram-Positive Cocci.htm?
22 Streptococcus.htm?
23 Enterococcus and Other Gram-Positive Cocci.htm?
24 Bacillus.htm?
25 Listeria and Erysipelothrix.htm?
26 Corynebacterium and Other Gram-Positive Rods.htm?
27 Nocardia and Related Bacteria.htm?
28 Mycobacterium.htm?
29 Neisseria and Related Bacteria.htm?
30 Enterobacteriaceae.htm?
31 Vibrio and Aeromonas.htm?
32 Campylobacter and Helicobacter.htm?
33 Pseudomonas and Related Bacteria.htm?
34 Haemophilus and Related Bacteria.htm?
35 Bordetella.htm?
36 Francisella and Brucella.htm?
37 Legionella.htm?
38 Miscellaneous Gram-Negative Rods.htm?
39 Clostridium.htm?
40 Anaerobic, Non-Spore-Forming, Gram-Positive Bacteria.htm?
41 Anaerobic Gram-Negative Bacteria.htm?
42 Treponema, Borrelia, and Leptospira.htm?
43 Mycoplasma and Ureaplasma.htm?
44 Rickettsia and Orientia.htm?

45 Ehrlichia, Anaplasma, and Coxiella.htm?
46 Chlamydia and Chlamydophila.htm?
47 Role of Bacteria in Disease.htm?
Section VI
48 Mechanisms of Viral Pathogenesis.htm?


49 Antiviral Agents.htm?
50 Laboratory Diagnosis of Viral Diseases.htm?
51 Papillomaviruses and Polyomaviruses.htm?
52 Adenoviruses.htm?
53 Human Herpesviruses.htm?
54 Poxviruses.htm?
55 Parvoviruses.htm?
56 Picornaviruses.htm?
57 Coronaviruses and Noroviruses.htm?
58 Paramyxoviruses.htm?
59 Orthomyxoviruses.htm?
60 Rhabdoviruses, Filoviruses, and Bornaviruses.htm?
61 Reoviruses.htm?
62 Togaviruses and Flaviviruses.htm?
63 Bunyaviridae and Arenaviridae.htm?
64 Retroviruses.htm?
65 Hepatitis Viruses.htm?
66 Unconventional Slow Viruses Prions.htm?
67 Role of Viruses in Disease.htm?
Section VII
68 Pathogenesis of Fungal Disease.htm?
69 Laboratory Diagnosis of Fungal Diseases.htm?
70 Antifungal Agents.htm?

71 Superficial and Cutaneous Mycoses.htm?
72 Subcutaneous Mycoses.htm?
73 Systemic Mycoses Due to Dimorphic Fungi.htm?
74 Opportunistic Mycoses.htm?
75 Fungal and Fungal-Like Infections of Unusual or Uncertain Etiology.htm?
76 Mycotoxins and Mycotoxicoses.htm?
77 Role of Fungi in Disease.htm?
Section VIII
78 Pathogenesis of Parasitic Diseases.htm?


79 Laboratory Diagnosis of Parasitic Disease.htm?
80 Antiparasitic Agents.htm?
81 Intestinal and Urogenital Protozoa.htm?
82 Blood and Tissue Protozoa.htm?
83 Nematodes.htm?
84 Trematodes.htm?
85 Cestodes.htm?
86 Arthropods.htm?
87 Role of Parasites in Disease.htm?
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Viruses
Viruses are the smallest infectious particles, ranging in diameter from
18 to 600 nanometers (most viruses are less than 200 nm and cannot
be seen with a light microscope). Viruses typically contain either
deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) but not both;
however, some viral-like particles do not contain any detectable
nucleic acids (e.g., prions; see Chapter 66), while the recently

discovered Mimivirus contains both RNA and DNA. The viral nucleic
acids and proteins required for replication and pathogenesis are
enclosed in a protein coat with or without a lipid membrane coat.
Viruses are true parasites, requiring host cells for replication. The
cells they infect and the host response to the infection dictate the
nature of the clinical manifestation. More than 2000 species of viruses
have been described, with approximately 650 infecting humans and
animals. Infection can lead either to rapid replication and destruction
of the cell or to a long-term chronic relationship with possible
integration of the viral genetic information into the host genome. The
factors that determine which of these takes place are only partially
understood. For example, infection with the human immunodeficiency
virus, the etiologic agent of the acquired immunodeficiency syndrome
(AIDS), can result in the latent infection of CD4 lymphocytes or the
active replication and destruction of these immunologically important
cells. Likewise, infection can spread to other susceptible cells, such
as the microglial cells of the brain, resulting in the neurologic
manifestations of AIDS. Thus the diseases caused by viruses can
range from the common cold to gastroenteritis to fatal catastrophes
such as rabies, Ebola, smallpox, or AIDS.
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Bacteria


Bacteria are relatively simple in structure. They are prokaryotic
organisms-simple unicellular organisms with no nuclear membrane,
mitochondria, Golgi bodies, or endoplasmic reticulum-that reproduce
by asexual division. The bacterial cell wall is complex, consisting of

one of two basic forms: a gram-positive cell wall with a thick
peptidoglycan layer, and a gram-negative cell wall with a thin
peptidoglycan layer and an overlying outer membrane (additional
information about this structure is presented in Chapter 2). Some
bacteria lack this cell wall structure and compensate by surviving only
inside host cells or in a hypertonic environment. The size (1 to 20 ?m
or larger), shape (spheres, rods, spirals), and spacial arrangement
(single cells, chains, clusters) of the cells are used for the preliminary
classification of bacteria, and the phenotypic and genotypic properties
of the bacteria form the basis for the definitive classification. The
human body is inhabited by thousands of different bacterial
species-some living transiently, others in a permanent parasitic
relationship. Likewise, the environment that surrounds us, including
the air we breathe, water we drink, and food we eat, is populated with
bacteria, many of which are relatively avirulent and some of which are
capable of producing life-threatening disease. Disease can result from
the toxic effects of bacterial products (e.g., toxins) or when bacteria
invade normally sterile body sites.
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Fungi


In contrast to bacteria, the cellular structure of fungi is more complex.
These are eukaryotic organisms that contain a well-defined nucleus,
mitochondria, Golgi bodies, and endoplasmic reticulum (see Chapter
5). Fungi can exist either in a unicellular form (yeast) that can
replicate asexually or in a filamentous form (mold) that can replicate
asexually and sexually. Most fungi exist as either yeasts or molds;

however, some fungi can assume either morphology. These are
known as dimorphic fungi and include such organisms as
Histoplasma, Blastomyces, and Coccidioides.
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Parasites
Parasites are the most complex microbes. Although all parasites are
classified as eukaryotic, some are unicellular and others are
multicellular (see Chapter 6). They range in size from tiny protozoa as
small as 1 to 2 ?m in diameter (the size of many bacteria) to
tapeworms that can measure up to 10 meters in length and
arthropods (bugs). Indeed, considering the size of some of these
parasites, it is hard to imagine how these organisms came to be
classified as microbes. Their life cycles are equally complex, with
some parasites establishing a permanent relationship with humans
and others going through a series of developmental stages in a
progression of animal hosts. One of the difficulties confronting
students is not only an understanding of the spectrum of diseases
caused by parasites, but also an appreciation of the epidemiology of
these infections, which is vital for developing a differential diagnosis
and an approach to the control and prevention of parasitic infections.
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Microbial Disease


One of the most important reasons for studying microbes is to
understand the diseases they cause and the ways to control them.

Unfortunately, the relationship between many organisms and their
diseases is not simple. Specifically, most organisms do not cause a
single, well-defined disease, although there are certainly ones that do
(e.g., Treponema pallidum, syphilis; poliovirus, polio; Plasmodium
species, malaria). Instead, it is more common for a particular
organism to produce many manifestations of disease (e.g.,
Staphylococcus aureus-endocarditis, pneumonia, wound infections,
food poisoning) or for many organisms to produce the same disease
(e.g., meningitis caused by viruses, bacteria, fungi, and parasites). In
addition, relatively few organisms can be classified as always
pathogenic, although some do belong in this category (e.g., rabies
virus, Bacillus anthracis, Sporothrix schenckii, Plasmodium species).
Instead, most organisms are able to establish disease only under
well-defined circumstances (e.g., the introduction of an organism with
a potential for causing disease into a normally sterile site such as the
brain, lungs, and peritoneal cavity). Some diseases arise when a
person is exposed to organisms from external sources. These are
known as exogenous infections, and examples include diseases
caused by influenza virus, Clostridium tetani, Neisseria gonorrhoeae,
Coccidioides immitis, and Entamoeba histolytica. Most human
diseases, however, are produced by organisms in the person's own
microbial flora that spread to inappropriate body sites where disease
can ensue (endogenous infections).
The interaction between an organism and the human host is complex.
The interaction can result in transient colonization, a long-term
symbiotic relationship, or disease. The virulence of the organism, the
site of exposure, and the host's ability to respond to the organism
determine the outcome of this interaction. Thus the manifestations of
disease can range from mild symptoms to organ failure and death.
The role of microbial virulence and the host's immunologic response

is discussed in depth in subsequent chapters.
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The human body is remarkably adapted to controlling exposure to
pathogenic microbes. Physical barriers prevent invasion by the
microbe; innate responses recognize molecular patterns on the
microbial components and activate local defenses and specific
adapted immune responses that target the microbe for elimination.
Unfortunately, the immune response is often too late or too slow. To
improve the human body's ability to prevent infection, the immune
system can be augmented either through the passive transfer of
antibodies present in immune globulin preparations or through active
immunization with components of the microbes (antigens). Infections
can also be controlled with a variety of chemotherapeutic agents.
Unfortunately, many microbes can alter their antigenic complexion
(antigenic variation) or develop resistance to even the most potent
antibiotics. Thus the battle for control between microbe and host
continues, with neither side yet able to claim victory (although the
microbes have demonstrated remarkable ingenuity). There clearly is
no "magic bullet" that has eradicated infectious diseases.
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Diagnostic Microbiology


The clinical microbiology laboratory plays an important role in the
diagnosis and control of infectious diseases. However, the ability of

the laboratory to perform these functions is limited by the quality of
the specimen collected from the patient, the means by which it is
transported from the patient to the laboratory, and the techniques
used to demonstrate the microbe in the sample. Because most
diagnostic tests are based on the ability of the organism to grow,
transport conditions must ensure the viability of the pathogen. In
addition, the most sophisticated testing protocols are of little value if
the collected specimen is not representative of the site of infection.
This seems obvious, but many specimens sent to laboratories for
analysis are contaminated during collection with the organisms that
colonize the mucosal surfaces. It is virtually impossible to interpret the
testing results with contaminated specimens, because most infections
are caused by endogenous organisms.
The laboratory is also able to determine the antimicrobial activity of
selected chemotherapeutic agents, although the value of these tests
is limited. The laboratory must test only organisms capable of
producing disease and only medically relevant antimicrobials. To test
all isolated organisms or an indiscriminate selection of drugs can yield
misleading results with potentially dangerous consequences. Not only
can a patient be treated inappropriately with unnecessary antibiotics,
but also the true pathogenic organism may not be recognized among
the plethora of organisms isolated and tested. Finally, the in vitro
determination of an organism's susceptibility to a variety of antibiotics
is only one aspect of a complex picture. The virulence of the
organism, site of infection, and patient's ability to respond to the
infection influence the host-parasite interaction and must also be
considered when planning treatment.
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Summary


It is important to realize that our knowledge of the microbial world is
evolving continually. Just as the early microbiologists built their
discoveries on the foundations established by their predecessors, we
and future generations will continue to discover new microbes, new
diseases, and new therapies. The following chapters are intended as
a foundation of knowledge that can be used to build your
understanding of microbes and their diseases.
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Bacterial Metabolism
Metabolic Requirements
Bacterial growth requires a source of energy and the raw materials to
build the proteins, structures, and membranes that make up and
power the cell. Bacteria must obtain or synthesize the amino acids,
carbohydrates, and lipids used as building blocks of the cell.
The minimum requirement for growth is a source of carbon and
nitrogen, an energy source, water, and various ions. The essential
elements include the components of proteins, lipids and nucleic acids
(C, O, H, N, S, P), important ions (K, Na, Mg, Ca, Cl) and components
of enzymes (Fe, Zn, Mn, Mo, Se, Co, Cu, Ni). Iron is so important that
many bacteria secrete special proteins (siderophores) to concentrate
iron from dilute solutions, and our bodies will sequester iron to reduce
its availability as a means of protection.

Oxygen (O2 gas), although essential for the human host, is actually a
poison for many bacteria. Some organisms, such as Clostridium
perfringens, which causes gas gangrene, cannot grow in the
presence of oxygen. Such bacteria are referred to as obligate
anaerobes. Other organisms, such as Mycobacterium tuberculosis,
which causes tuberculosis, require the presence of molecular oxygen
for metabolism and growth and are therefore referred to as obligate
aerobes. Most bacteria, however, grow in either the presence or the
absence of oxygen. These bacteria are referred to as facultative
anaerobes. Aerobic bacteria produce superoxide dismutase and
catalase enzymes which can detoxify hydrogen peroxide and
superoxide radicals that are the toxic byproducts of aerobic
metabolism.


Growth requirements and metabolic byproducts may be used as a
convenient means of classifying different bacteria. Some bacteria,
such as certain strains of Escherichia coli (a member of the intestinal
flora), can synthesize all the amino acids, nucleotides, lipids, and
carbohydrates necessary for growth and division, whereas the growth
requirements of the causative agent of syphilis, Treponema pallidum,
are so complex that a defined laboratory medium capable of
supporting its growth has yet to be developed. Bacteria that can rely
entirely on inorganic chemicals for their energy and source of carbon
(CO2) are referred to as autotrophs (lithotrophs), whereas many
bacteria and animal cells that require organic carbon sources are
known as heterotrophs (organotrophs). Clinical microbiology
laboratories distinguish bacteria by their ability to grow on specific
carbon sources (e.g., lactose) and the end products of metabolism
(e.g., ethanol, lactic acid, succinic acid).

Metabolism, Energy, and Biosynthesis
All cells require a constant supply of energy to survive. This energy,
typically in the form of adenosine triphosphate (ATP), is derived from
the controlled breakdown of various organic substrates
(carbohydrates, lipids, and proteins). This process of substrate
breakdown and conversion into usable energy is known as
catabolism. The energy produced may then be used in the synthesis
of cellular constituents (cell walls, proteins, fatty acids, and nucleic
acids), a process known as anabolism. Together these two
processes, which are interrelated and tightly integrated, are referred
to as intermediary metabolism.


The metabolic process generally begins with hydrolysis of large
macromolecules in the external cellular environment by specific
enzymes (Figure 3-1). The smaller molecules that are produced (e.g.,
monosaccharides, short peptides, and fatty acids) are transported
across the cell membranes into the cytoplasm by active or passive
transport mechanisms specific for the metabolite. These mechanisms
may use specific carrier or membrane transport proteins to help
concentrate metabolites from the medium. The metabolites are
converted via one or more pathways to one common, universal
intermediate, pyruvic acid. From pyruvic acid the carbons may be
channeled toward energy production or the synthesis of new
carbohydrates, amino acids, lipids, and nucleic acids.
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Figure 3-1 Catabolism of proteins, polysaccharides, and lipids produces glucose,
pyruvate, or intermediates of the tricarboxylic acid (TCA) cycle and, ultimately,
energy in the form of adenosine triphosphate (ATP) or the reduced form of
nicotinamide-adenine dinucleotide (NADH).

Metabolism of Glucose
For the sake of simplicity, this section presents an overview of the
pathways by which glucose is metabolized to produce energy or other
usable substrates. Instead of releasing all the molecule's energy as
heat (as for burning), the bacteria break down the glucose in discrete
steps to allow the energy to be captured in usable forms. Bacteria can
produce energy from glucose by-in order of increasing
efficiency-fermentation, anaerobic respiration (both of which occur in
the absence of oxygen), or aerobic respiration. Aerobic respiration
can completely convert the six carbons of glucose to CO2 and H2O
plus energy, whereas two- and three-carbon compounds are the end
products of fermentation. For a more complete discussion of
metabolism, please refer to a textbook on biochemistry.

Embden-Meyerhof-Parnas Pathway
Bacteria use three major metabolic pathways in the catabolism of
glucose. Most common among these is the glycolytic, or
Embden-Meyerhof-Parnas (EMP), pathway (Figure 3-2) for the
conversion of glucose to pyruvate. These reactions, which occur
under both aerobic and anaerobic conditions, begin with activation of
glucose to form glucose-6-phosphate. This reaction, as well as the
third reaction in the series, in which fructose-6-phosphate is converted
to fructose-1,6-diphosphate, requires 1 mole of ATP per mole of
glucose and represents an initial investment of cellular energy stores.

Figure 3-2 Embden-Meyerhof-Parnas (EMP) glycolytic pathway results in
conversion of glucose to pyruvate. ADP, adenosine diphosphate; ATP, adenosine
triphosphate; iPO4, inorganic phosphate; NAD, nicotinamide adenine
dinucleotide; NADH, reduced form of NAD.
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Figure 3-3 Fermentation of pyruvate by different microorganisms results in
different end products. The clinical laboratory uses these pathways and end
products as a means of distinguishing different bacteria.


Energy is produced during glycolysis in two different forms, chemical
and electrochemical. In the first, the high-energy phosphate group of
one of the intermediates in the pathway is used under the direction of
the appropriate enzyme (a kinase) to generate ATP from adenosine
diphosphate (ADP). This type of reaction, termed substrate-level
phosphorylation, occurs at two different points in the glycolytic
pathway (i.e., conversion of 3-phosphoglycerol phosphate to
3-phosphoglycerate and 2-phosphoenolpyruvic acid to pyruvate). Four
ATP molecules per molecule of glucose are produced in this manner,
but two ATP molecules were used in the initial glycolytic conversion of
glucose to two molecules of pyruvic acid, resulting in a net production
of two molecules of ATP. The reduced form of nicotinamide-adenine
dinucleotide (NADH) that is produced represents the second form of
energy, which may then be converted to ATP by a series of oxidation
reactions.
In the absence of oxygen, substrate-level phosphorylation represents

the primary means of energy production. The pyruvic acid produced
from glycolysis is then converted to various end products, depending
on the bacterial species, in a process known as fermentation. Many
bacteria are identified on the basis of their fermentative end products
(Figure 3-3). These organic molecules, rather than oxygen, are used
as electron acceptors to recycle the NADH, which was produced
during glycolysis, to NAD. In yeast, fermentative metabolism results in
the conversion of pyruvate to ethanol plus carbon dioxide. Alcoholic
fermentation is uncommon in bacteria, which most commonly use the
one-step conversion of pyruvic acid to lactic acid. This process is
responsible for making milk into yogurt and cabbage into sauerkraut.
Other bacteria use more complex fermentative pathways, producing
various acids, alcohols, and often gases (many of which have vile
odors). These products lend flavors to various cheeses and wines and
odors to wound and other infections.

Tricarboxylic Acid Cycle


Figure 3-4 Tricarboxylic acid cycle occurs in aerobic conditions and is an
amphibolic cycle. Precursors for the synthesis of amino acids and nucleotides are
also shown. CoA, coenzyme A; FADH2, flavin adenine dinucleotide; GTP,
guanosine triphosphate.


In the presence of oxygen, the pyruvic acid produced from glycolysis
and from the metabolism of other substrates may be completely
oxidized (controlled burning) to water and CO2 using the tricarboxylic
acid (TCA) cycle (Figure 3-4), which results in production of additional
energy. The process begins with the oxidative decarboxylation

(release of CO2) of pyruvate to the high-energy intermediate, acetyl
coenzyme A (acetyl CoA); this reaction also produces two NADH
molecules. The two remaining carbons derived from pyruvate then
enter the TCA cycle in the form of acetyl CoA by condensation with
oxaloacetate, with the formation of the six-carbon citrate molecule. In
a stepwise series of oxidative reactions the citrate is converted back
to oxaloacetate. The theoretical yield from each pyruvate is 2 moles of
CO2, 3 moles of NADH, 1 mole of flavin adenine dinucleotide
(FADH2), and 1 mole of guanosine triphosphate (GTP).
The TCA cycle allows the organism to generate substantially more
energy per mole of glucose than is possible from glycolysis alone. In
addition to the GTP (an ATP equivalent) produced by substrate-level
phosphorylation, the NADH and FADH2 yield ATP from the electron
transport chain. In this chain the electrons carried by NADH (or
FADH2) are passed in a stepwise fashion through a series of
donor-acceptor pairs and ultimately to oxygen (aerobic respiration)
or other terminal electron acceptor (nitrate, sulfate, carbon dioxide,
ferric iron) (anaerobic respiration).
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Figure 3-5 Aerobic glucose metabolism. The theoretical maximum amount of ATP
obtained from one glucose molecule is 38, but the actual yield depends on the
organism and other conditions.

Anaerobic organisms are less efficient at energy production than
aerobic organisms. Fermentation produces only 2 ATP molecules per
glucose, whereas aerobic metabolism with electron transport and a
complete TCA cycle can generate as much as 19 times more energy

(38 ATP molecules) from the same starting material (and it is much
less smelly) (Figure 3-5). Anaerobic respiration uses organic
molecules as electron acceptors, which produces less ATP for each
NADH.


In addition to the efficient generation of ATP from glucose (and other
carbohydrates), the TCA cycle provides a means by which carbons
derived from lipids (in the form of acetyl CoA) may be shunted toward
either energy production or the generation of biosynthetic precursors.
Similarly, the cycle includes several points at which deaminated
amino acids may enter (see Figure 3-4). For example, deamination
of glutamic acid yields α-ketoglutarate, whereas deamination of
aspartic acid yields oxaloacetate, both of which are TCA cycle
intermediates. The TCA cycle therefore serves the following functions:
1. It is the most efficient mechanism for the generation of ATP.
2. It serves as the final common pathway for the complete oxidation
of amino acids, fatty acids, and carbohydrates.
3. It supplies key intermediates (i.e., α-ketoglutarate, pyruvate,
oxaloacetate) for the ultimate synthesis of amino acids, lipids,
purines, and pyrimidines.
The last two functions make the TCA cycle a so-called amphibolic
cycle (i.e., it may function in the anabolic and the catabolic functions
of the cell).

Pentose Phosphate Pathway


The final pathway of glucose metabolism considered here is known as
the pentose phosphate pathway, or the hexose monophosphate

shunt. The function of this pathway is to provide nucleic acid
precursors and reducing power in the form of nicotinamide-adenine
dinucleotide phosphate (reduced form) (NADPH) for use in
biosynthesis. In the first half of the pathway, glucose is converted to
ribulose-5-phosphate, with consumption of 1 mole of ATP and
generation of 2 moles of NADPH per mole of glucose. The
ribulose-5-phosphate may then be converted to ribose-5-phosphate (a
precursor in nucleotide biosynthesis) or alternatively to
xylulose-5-phosphate. The remaining reactions in the pathway use
enzymes known as transketolases and transaldolases to generate
various sugars, which may function as biosynthetic precursors or may
be shunted back to the glycolytic pathway for use in energy
generation.
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The Bacterial Genes and Expression
The bacterial genome is the total collection of genes carried by a
bacterium, both on its chromosome and on its extrachromosomal
genetic elements, if any. Genes are sequences of nucleotides that
have a biologic function; examples are protein-structural genes
(cistrons, which are coding genes), ribosomal ribonucleic acid (RNA)
genes, and recognition and binding sites for other molecules
(promoters and operators). Each genome contains many operons,
which are made up of genes. Eukaryotes usually have two distinct
copies of each chromosome (they are therefore diploid). Bacteria
usually have only one copy of their chromosomes (they are therefore
haploid). Because bacteria have only one chromosome, alteration of
a gene (mutation) will have a more obvious effect on the cell. In
addition, the structure of the bacterial chromosome is maintained by

polyamines, such as spermine and spermidine, rather than by
histones.


Bacteria may also contain extrachromosomal genetic elements
such as plasmids or bacteriophages (bacterial viruses). These
elements are independent of the bacterial chromosome and in most
cases can be transmitted from one cell to another.

Transcription
The information carried in the genetic memory of the DNA is
transcribed into a useful messenger RNA (mRNA) for subsequent
translation into protein. RNA synthesis is performed by a
DNA-dependent RNA polymerase.
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The process begins when sigma factor recognizes a particular
sequence of nucleotides in the DNA (the promoter) and binds tightly
to this site. Promoter sequences occur just before the start of the DNA
that actually encodes a protein. Sigma factors bind to these promoters
to provide a docking site for the RNA polymerase. Some bacteria
encode several sigma factors to allow transcription of a group of
genes under special conditions, such as heat shock, starvation,
special nitrogen metabolism, or sporulation. Once the polymerase has
bound to the appropriate site on the DNA, RNA synthesis proceeds
with the sequential addition of ribonucleotides complementary to the
sequence in the DNA. Once an entire gene or group of genes
(operon) has been transcribed, the RNA polymerase dissociates from
the DNA, a process mediated by signals within the DNA. The

bacterial, DNA-dependent RNA polymerase is inhibited by rifampin,
an antibiotic often used in the treatment of tuberculosis. The transfer
RNA (tRNA), which is used in protein synthesis, and ribosomal RNA
(rRNA), a component of the ribosomes, are also transcribed from the
DNA.