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PEARLS

The agents of human infectious diseases are bacteria, fungi (yeasts and molds), protozoa, helminths (worms), and viruses.

Bacteria, fungi, protozoa, and helminths are composed of cells, whereas viruses are noncellular.

Bacterial cells do not have a membrane­bound nucleus, whereas human, fungal, protozoan, and helminths cells do have a membrane­bound
nucleus.

All cells contain both DNA and RNA, whereas viruses contain either DNA or RNA, but not both.

In addition to a flexible membrane, bacterial and fungal cells are surrounded by a rigid cell wall, whereas human, protozoan, and helminth
cells are bounded only by a flexible cell membrane.

Most bacteria have cell walls that contain peptidoglycan, whereas fungal cell walls contain chitin.
Review of Medical Microbiology & Immunology: A Guide to Clinical Infectious Diseases, 17e

Chapter 2: Structure of Bacterial Cells

SHAPE & SIZE OF BACTERIA

Bacteria are classified by shape into three basic groups: cocci (round), bacilli (rods), and spirochetes (spiral shaped) (Figure 2–1). Some
bacteria are variable in shape and are said to be pleomorphic (heterogeneous shape). The shape of a bacterium is determined by its rigid cell wall.
The microscopic appearance of a bacterium is one of the most important criteria used in its identification.

FIGURE 2–1

Bacterial morphology. A : Cocci in clusters (e.g., Staphylococcus; A­1); in chains (e.g., Streptococcus; A­2); in pairs with pointed ends (e.g.,
Streptococcus pneumoniae; A­3); in pairs with kidney bean shape (e.g., Neisseria; A­4). B : Rods (bacilli): with square ends (e.g., Bacillus; B­1); with
rounded ends (e.g., Salmonella; B­2); club­shaped (e.g., Corynebacterium; B­3); fusiform (e.g., Fusobacterium; B­4); comma­shaped (e.g., Vibrio; B­5).
C : Spirochetes: spiral shape with relaxed coils (e.g., Borrelia; C­1); spiral shape with tight coils (e.g., Treponema; C­2). (Reproduced with permission
from Joklik WK, Willett HP, Amos DB: Zinsser Microbiology, 20th ed. New York, NY: McGraw Hill; 1992.)

In addition to their characteristic shapes, the arrangement of bacteria is important. For example, certain cocci occur in pairs (diplococci), some in
chains (streptococci), and others in grapelike clusters (staphylococci). The arrangement of rods and spirochetes is medically less important.

Bacteria range in size from about 0.2 to 5 μm (Figure 2–2). The smallest bacteria (Mycoplasma) are about the same size as the largest viruses
(poxviruses) and are the smallest organisms capable of existing outside a host. The longest bacteria are the size of some yeasts and human red blood
cells (7 μm).

FIGURE 2–2

Sizes of representative bacteria, viruses, yeasts, protozoa, and human red cells. The bacteria range in size from Mycoplasma, the smallest, to Bacillus
anthracis, one of the largest. The viruses range from poliovirus, one of the smallest, to poxviruses. Yeasts, such as Candida albicans, are generally
larger than bacteria. Protozoa have many different forms and a broad size range. HIV, human immunodeficiency virus. (Reproduced with permission
from Joklik WK, Willett HP, Amos DB: Zinsser Microbiology, 20th ed. New York, NY: McGraw Hill; 1992.)
STRUCTURE OF BACTERIA
The structure of a typical bacterium is illustrated in Figure 2–3, and the important features of each component are presented in Table 2–1.

FIGURE 2–3

Bacterial structure. (Reproduced with permission from Ryan K: Sherris Medical Microbiology, 4th ed. New York, NY: McGraw Hill; 2004.)

TABLE 2–1
Bacterial Structures

Structure Chemical Composition Function

Essential components

Cell wall

Peptidoglycan Glycan (sugar) backbone with peptide Gives rigid support, protects against osmotic pressure, is the site of action of
side chains that are cross­linked penicillins and cephalosporins, and is degraded by lysozyme

Outer membrane of 1. Lipid A Toxic component of endotoxin

gram­negative bacteria 2. Polysaccharide Major surface antigen used frequently in laboratory diagnosis

Surface fibers of gram­ Teichoic acid Major surface antigen but rarely used in laboratory diagnosis
 TABLE 2–1
Bacterial Structures

Structure Chemical Composition Function

Essential components

Cell wall

Peptidoglycan Glycan (sugar) backbone with peptide Gives rigid support, protects against osmotic pressure, is the site of action of
side chains that are cross­linked penicillins and cephalosporins, and is degraded by lysozyme

Outer membrane of 1. Lipid A Toxic component of endotoxin

gram­negative bacteria 2. Polysaccharide Major surface antigen used frequently in laboratory diagnosis

Surface fibers of gram­ Teichoic acid Major surface antigen but rarely used in laboratory diagnosis
positive bacteria

Plasma membrane Lipoprotein bilayer without sterols Site of oxidative and transport enzymes

Ribosome RNA and protein in 50S and 30S subunits Protein synthesis; site of action of aminoglycosides, erythromycin, tetracyclines,
and chloramphenicol

Nucleoid DNA Genetic material

Mesosome Invagination of plasma membrane Participates in cell division and secretion

Periplasm Space between plasma membrane and Contains many hydrolytic enzymes, including β­lactamases
outer membrane

Nonessential components

Capsule Typically polysaccharide Protects against phagocytosis

Pilus or fimbria Glycoprotein Two types: (1) mediates attachment to cell surfaces; (2) sex pilus mediates
attachment of two bacteria during conjugation

Flagellum Protein Motility

Spore Keratin­like coat, dipicolinic acid Provides resistance to dehydration, heat, and chemicals

Plasmid DNA Contains a variety of genes for antibiotic resistance and toxins

Granule Glycogen, lipids, polyphosphates Site of nutrients in cytoplasm

Glycocalyx Polysaccharide Mediates adherence to surfaces

Cell Wall

The cell wall is the outermost component common to all bacteria (except Mycoplasma species, which are bounded by a cell membrane, not a cell wall).
The cell wall is the outermost component common to all bacteria (except Mycoplasma species, which are bounded by a cell membrane, not a cell wall).
Some bacteria have surface features external to the cell wall, such as capsule, flagella, and pili, which are less common components and are discussed
next.

The cell wall is located external to the cytoplasmic membrane and is composed of peptidoglycan. The peptidoglycan provides structural support and
maintains the characteristic shape of the cell.

Cell Walls of Gram­Positive and Gram­Negative Bacteria

The structure, chemical composition, and thickness of the cell wall differ in gram­positive and gram­negative bacteria (Table 2–2, Figure 2–4A, and
“Gram Stain” box).

1. The peptidoglycan layer is much thicker in gram­positive than in gram­negative bacteria. Many gram­positive bacteria also have fibers of teichoic
acid that protrude outside the peptidoglycan, whereas gram­negative bacteria do not have teichoic acids.

2. In contrast, the gram­negative bacteria have a complex outer layer consisting of lipopolysaccharide (LPS), lipoprotein, and phospholipid. Together
with the cell wall, this gram­negative architecture is referred to as the “envelope.” Lying between the outer­membrane layer and the cytoplasmic
membrane in gram­negative bacteria is the periplasmic space, which is the site, in some species, of enzymes called β­lactamases that degrade
penicillins and other β­lactam drugs.

TABLE 2–2
Comparison of Cell Walls of Gram­Positive and Gram­Negative Bacteria

Component Gram­Positive Cells Gram­Negative Cells

Peptidoglycan Thicker; multilayer Thinner; few layers

Teichoic acids Yes No

Lipopolysaccharide (endotoxin) No Yes

FIGURE 2–4

Bacterial cell wall structure. A : Cell walls of gram­positive and gram­negative bacteria. Note that the peptidoglycan in gram­positive bacteria is much
thicker than in gram­negative bacteria. Note also that only gram­negative bacteria have an outer membrane containing endotoxin (lipopolysaccharide
[LPS]) and thus have a periplasmic space where β­lactamases are found. Several important gram­positive bacteria, such as staphylococci and
streptococci, have teichoic acids. B : Cell wall of Mycobacterium tuberculosis: Note the layers of mycolic acid and arabinoglycan that are present in
members of the genus Mycobacterium but not in most other genera of bacteria. (A, Reproduced with permission from Ingraham JL, Maaløe O,
Neidhardt FC: Growth of the Bacterial Cell. Sunderland, MA: Sinauer Associates; 1983.)
GRAM STAIN

This staining procedure, developed in 1884 by the Danish physician Christian Gram, is the most important staining procedure in microbiology. It
separates most bacteria into two groups: the gram­positive bacteria, which stain purple, and the gram­negative bacteria, which stain red. The Gram
stain involves the following four­step procedure:

1. The crystal violet dye stains all cells purple.

2. The iodine solution (a mordant) is added to form a crystal violet–iodine complex; all cells continue to appear purple.

3. The organic solvent, such as acetone or ethanol, extracts the purple dye/iodine complex from the lipid­rich, thin­walled, gram­negative bacteria
to a greater degree than from the lipid­poor, thick­walled, gram­positive bacteria. The gram­negative organisms appear colorless; the gram­
positive bacteria remain purple.

4. The red dye safranin stains the decolorized gram­negative cells red/pink; the gram­positive bacteria remain purple.

The Gram stain is useful in two ways:

1. In the identification of many bacteria.

2. In influencing the choice of antibiotic because, in general, gram­positive bacteria are more susceptible to penicillin G than are gram­negative
bacteria.

However, not all bacteria can be seen in the Gram stain. Table 2–3 lists the medically important bacteria that cannot be seen and describes the
reason why. The alternative microscopic approach to the Gram stain is also described.

Note that it takes approximately 100,000 bacteria/mL to see 1 bacterium per microscopic field using the oil immersion (100×) lens. So the sensitivity
of the Gram stain procedure is low. This explains why a patient’s blood is rarely stained immediately but rather is incubated in blood cultures
overnight to allow the bacteria to multiply. One important exception to this is meningococcemia in which very high concentrations of Neisseria
 GRAM STAIN

This staining procedure, developed in 1884 by the Danish physician Christian Gram, is the most important staining procedure in microbiology. It
separates most bacteria into two groups: the gram­positive bacteria, which stain purple, and the gram­negative bacteria, which stain red. The Gram
stain involves the following four­step procedure:

1. The crystal violet dye stains all cells purple.

2. The iodine solution (a mordant) is added to form a crystal violet–iodine complex; all cells continue to appear purple.

3. The organic solvent, such as acetone or ethanol, extracts the purple dye/iodine complex from the lipid­rich, thin­walled, gram­negative bacteria
to a greater degree than from the lipid­poor, thick­walled, gram­positive bacteria. The gram­negative organisms appear colorless; the gram­
positive bacteria remain purple.

4. The red dye safranin stains the decolorized gram­negative cells red/pink; the gram­positive bacteria remain purple.

The Gram stain is useful in two ways:

1. In the identification of many bacteria.

2. In influencing the choice of antibiotic because, in general, gram­positive bacteria are more susceptible to penicillin G than are gram­negative
bacteria.

However, not all bacteria can be seen in the Gram stain. Table 2–3 lists the medically important bacteria that cannot be seen and describes the
reason why. The alternative microscopic approach to the Gram stain is also described.

Note that it takes approximately 100,000 bacteria/mL to see 1 bacterium per microscopic field using the oil immersion (100×) lens. So the sensitivity
of the Gram stain procedure is low. This explains why a patient’s blood is rarely stained immediately but rather is incubated in blood cultures
overnight to allow the bacteria to multiply. One important exception to this is meningococcemia in which very high concentrations of Neisseria
meningitidis can occur in the blood.

TABLE 2–3
Medically Important Bacteria That Cannot Be Seen in the Gram Stain

Name Reason Alternative Microscopic Approach

Mycobacteria, including M. tuberculosis Too much lipid in cell wall so dye cannot penetrate Acid­fast stain

Treponema pallidum Too thin to see Dark­field microscopy or fluorescent antibody

Mycoplasma pneumoniae No cell wall; very small None

Legionella pneumophila Poor uptake of red counterstain Prolong time of counterstain

Chlamydiae, including C. trachomatis Intracellular; very small Inclusion bodies in cytoplasm

Rickettsiae Intracellular; very small Giemsa or other tissue stains

The cell wall in gram­positive organisms or cell envelope in gram­negative organisms has several other important properties:

1. In gram­negative bacteria, the envelope contains endotoxin, an LPS (see Chapter 7).
1. In gram­negative bacteria, the envelope contains endotoxin, an LPS (see Chapter 7).

2. Both gram­positive and gram­negative bacteria contain polysaccharides and proteins on their surface that are antigens useful in laboratory
identification.

3. Porin proteins play a role in facilitating the passage of small, hydrophilic molecules into the cell. Several types of porin proteins can be found in
the outer membrane of gram­negative bacteria, allowing the entry of essential substances such as sugars, amino acids, vitamins, and metals as well
as many antimicrobial drugs such as penicillins. Porins have also been identified in gram­positive bacteria, where they are anchored to the cell wall.

Cell Walls of Acid­Fast Bacteria

Mycobacteria (e.g., Mycobacterium tuberculosis) have an unusual cell wall, resulting in their inability to be Gram­stained (Figure 2–4B). These bacteria
are said to be acid­fast because they resist decolorization with acid–alcohol after being stained with carbolfuchsin. This property is related to the high
concentration of lipids, called mycolic acids, in the cell wall of mycobacteria.

Note that Nocardia asteroides, a bacterium that can cause lung and brain infections in immunocompromised individuals, is weakly acid­fast. The
meaning of the term “weakly” is that if the acid­fast staining process uses a weaker solution of hydrochloric acid to decolorize than that used in the
stain for mycobacteria, then N. asteroides will not decolorize. However, if the regular­strength hydrochloric acid is used, N. asteroides will decolorize.

In view of their importance, three components of the cell wall (i.e., peptidoglycan, LPS, and teichoic acid) are discussed in detail here.

Peptidoglycan

Peptidoglycan is a complex, interwoven network that surrounds the entire cell and is composed of a single covalently linked macromolecule. It is found
only in bacterial cell walls. It provides rigid support for the cell, is important in maintaining the characteristic shape of the cell, and allows the cell to
withstand low osmotic pressure. A representative segment of the peptidoglycan layer is shown in Figure 2–5. The term peptidoglycan is derived from
the peptides and the sugars (glycan) that make up the molecule. Synonyms for peptidoglycan are murein and mucopeptide.

FIGURE 2–5

Peptidoglycan structure. A : Peptidoglycan is composed of a glycan chain (NAM and NAG), a tetrapeptide chain, and a cross­link (peptide interbridge).
B : In the cell wall, the peptidoglycan forms a multilayered, three­dimensional structure. NAG, N­acetylglucosamine; NAM, N­acetylmuramic acid.
(Reproduced with permission from Nester EW, Anderson D, Roberts CE, et al: Microbiology: A Human Perspective, 6th ed. New York, NY: McGraw Hill;
2009.)
Figure 2–5 illustrates the carbohydrate backbone, which is composed of alternating N­acetylmuramic acid and N­acetylglucosamine molecules.
Attached to each of the muramic acid molecules is a tetrapeptide consisting of both D­ and L­amino acids, the precise composition of which differs from
one bacterium to another. Two of these amino acids are worthy of special mention: diaminopimelic acid, which is unique to bacterial cell walls, and D­
alanine, which is involved in the cross­links between the tetrapeptides and in the action of penicillin. Note that this tetrapeptide contains the rare D­
isomers of amino acids; most proteins contain the L­isomer. The other important component in this network is the peptide cross­link between the two
tetrapeptides. The cross­links vary among species; in Staphylococcus aureus, for example, five glycines link the terminal D­alanine to the penultimate L­
lysine.

Because peptidoglycan is present in bacteria but not in human cells, it is a good target for antibacterial drugs. Several of these drugs, such as
i illi h l i d i i hibit th th i f tid l b i hibiti th t tid th t k th li k
Because peptidoglycan is present in bacteria but not in human cells, it is a good target for antibacterial drugs. Several of these drugs, such as
penicillins, cephalosporins, and vancomycin, inhibit the synthesis of peptidoglycan by inhibiting the transpeptidase that makes the cross­links
between the two adjacent tetrapeptides (see Chapter 10 for a description of these antibiotics).

Lysozyme, an enzyme present in human tears, mucus, and saliva, can cleave the peptidoglycan backbone by breaking its glycosyl bonds, thereby
contributing to the natural resistance of the host to microbial infection. Lysozyme­treated bacteria may swell and rupture as a result of the entry of
water into the cells, which have a high internal osmotic pressure.

Lipopolysaccharide

The LPS of the outer membrane of the cell wall of gram­negative bacteria is endotoxin. It is responsible for many of the features of the disease, such
as fever and shock (especially hypotension), caused by these organisms (see Chapter 7). It is called endotoxin because it is an integral part of the cell
envelope, in contrast to exotoxins, which are actively secreted from the bacteria. The constellation of symptoms caused by the endotoxin of one gram­
negative bacterium is similar to another, but the severity of the symptoms can differ greatly. In contrast, the symptoms caused by exotoxins of different
bacteria are usually quite different.

The LPS is composed of three distinct units (Figure 2–6):

1. A phospholipid called lipid A, which is responsible for the toxic effects.

2. A core polysaccharide of five sugars linked to lipid A.

3. An outer polysaccharide consisting of up to 25 repeating units of three to five sugars. This outer polymer is the important somatic, or O, antigen of
several gram­negative bacteria that is used to identify certain organisms in the clinical laboratory. Some bacteria, notably members of the genus
Neisseria, have an outer lipooligosaccharide (LOS) containing very few repeating units of sugars.

FIGURE 2–6

Endotoxin (lipopolysaccharide [LPS]) structure. The O­antigen polysaccharide is exposed on the exterior of the cell, whereas the lipid A faces the
interior. (Reproduced with permission from Brooks GF, Jawetz E: Medical Microbiology, 19th ed. New York, NY: McGraw Hill; 1991.)

Teichoic Acid

Teichoic acids and lipoteichoic acids are fibers anchored to the cell wall or cell membrane, respectively, that extend from the outer layer of the gram­
positive cell wall. The medical importance of teichoic acids lies in their ability to induce inflammation and septic shock when caused by certain
gram­positive bacteria; that is, they activate the same pathways as does endotoxin (LPS) in gram­negative bacteria. Teichoic acids also mediate the
attachment of staphylococci to mucosal cells. Gram­negative bacteria do not have teichoic acids.
Cytoplasmic Membrane

Just inside the peptidoglycan layer of the cell wall lies the cytoplasmic membrane, which is composed of a phospholipid bilayer similar in microscopic
appearance to that in eukaryotic cells. They are chemically similar, but eukaryotic membranes contain sterols, whereas prokaryotes generally do not.
The only prokaryotes that have sterols in their membranes are members of the genus Mycoplasma. The membrane has four important functions: (1)
active transport of molecules into the cell, (2) energy generation by oxidative phosphorylation, (3) synthesis of precursors of the cell wall, and (4)
secretion of enzymes and toxins.

Cytoplasm

The cytoplasm has two distinct areas when seen in the electron microscope:

1. An amorphous matrix that contains ribosomes, nutrient granules, metabolites, and plasmids.

2. An inner, nucleoid region composed of DNA.

Ribosomes

Bacterial ribosomes are the site of protein synthesis as in eukaryotic cells, but they differ from eukaryotic ribosomes in size and chemical composition.
Bacterial ribosomes are 70S in size, with 50S and 30S subunits, whereas eukaryotic ribosomes are 80S in size, with 60S and 40S subunits. The
differences in both the ribosomal RNAs and proteins constitute the basis of the selective action of several antibiotics that inhibit bacterial, but not
human, protein synthesis (see Chapter 10 for a description of these antibiotics).

Nucleoid

The nucleoid is the area of the cytoplasm in which DNA is located. The DNA of most prokaryotes is a single, circular molecule; however, there are
important exceptions. For instance, the genome of Vibrio cholerae, the causative agent of cholera, is composed of two circular chromosomes. Borrelia
burgdorferi, the spirochete that causes Lyme disease, is composed of a linear chromosome and multiple circular and linear plasmids (see below). The
size of bacterial genomes varies widely, with the smallest genome containing just over 130 genes and the largest containing approximately 11,600
genes. By contrast, human DNA has approximately 25,000 genes.

Because the bacterial nucleoid contains no nuclear membrane, no nucleolus, no mitotic spindle, and no histones, there is little resemblance to the
eukaryotic nucleus. One major difference between bacterial DNA and eukaryotic DNA is that bacterial DNA has no introns, whereas eukaryotic DNA
does.

Plasmids

Plasmids are double­stranded, circular DNA molecules that are capable of replicating independently of the bacterial chromosome. Although plasmids
are usually extrachromosomal, they can be integrated into the bacterial chromosome. Plasmids occur in both gram­positive and gram­negative
bacteria, and several different types of plasmids can exist in one cell:

1. Transmissible plasmids can be transferred from cell to cell by conjugation (see Chapter 4 for a discussion of conjugation). They are large
(molecular weight [MW] 40–100 million) since they contain about a dozen genes responsible for synthesis of the sex pilus and for the enzymes
required for transfer. They are usually present in a few (1–3) copies per cell.

2. Nontransmissible plasmids are small (MW 3–20 million) since they do not contain the transfer genes; they are frequently present in many (10–60)
copies per cell.

Plasmids carry the genes for the following functions and structures of medical importance:

1. Antibiotic resistance, which is mediated by a variety of enzymes, such as the β­lactamase of S. aureus, Escherichia coli, and Klebsiella pneumoniae.

2. Exotoxins, such as the enterotoxins of E. coli, anthrax toxin of Bacillus anthracis, exfoliative toxin of S. aureus, and tetanus toxin of Clostridium
tetani.
2. Exotoxins, such as the enterotoxins of E. coli, anthrax toxin of Bacillus anthracis, exfoliative toxin of S. aureus, and tetanus toxin of Clostridium
tetani.

3. Pili (fimbriae), which mediate the adherence of bacteria to epithelial cells.

4. Resistance to heavy metals, such as mercury, the active component of some antiseptics (e.g., Merthiolate and Mercurochrome), and silver, which is
mediated by a reductase enzyme.

5. Resistance to ultraviolet light, which is mediated by DNA repair enzymes.

6. Bacteriocins, which are toxic proteins produced by certain bacteria that are lethal for other bacteria. Two common mechanisms of action of
bacteriocins are (i) degradation of bacterial cell membranes by producing pores in the membrane and (ii) degradation of bacterial DNA by
deoxyribonuclease (DNase). Examples of bacteriocins produced by medically important bacteria are colicins made by E. coli, pyocins made by
Pseudomonas aeruginosa and lysostaphins made by S. aureus. Bacteria that produce bacteriocins have a selective advantage in the competition
for food sources over those that do not. The medical importance of bacteriocins is that they may be useful in treating infections caused by
antibiotic­resistant bacteria.

Transposons

Transposons are pieces of DNA that move readily from one site to another either within or between the DNAs of bacteria, plasmids, and
bacteriophages. Because of their unusual ability to move, they are nicknamed “jumping genes.” Transposons can code for drug­resistant enzymes,
toxins, or a variety of metabolic enzymes and can either cause mutations in the gene into which they insert or alter the expression of nearby genes.

Transposons typically have four identifiable domains. On each end is a short DNA sequence of inverted repeats, which are involved in the
integration of the transposon into the recipient DNA. The second domain is the gene for the transposase, which is the enzyme that mediates the
excision and integration processes. The third region is the gene for the repressor that regulates the synthesis of both the transposase and the protein
encoded by the fourth domain, which, in many cases, is an enzyme mediating antibiotic resistance (Figure 2–7). Note that for simplicity, the repressor
gene is not shown in Figure 2–7.

FIGURE 2–7

Transposon genes. This transposon is carrying a drug­resistance gene. IR, inverted repeat. (Reproduced with permission from Willey JM, Sherwood L,
Woolverton: Prescott’s Principles of Microbiology. New York, NY: McGraw Hill; 2009.)

Antibiotic resistance genes are transferred from one bacterium to another primarily by conjugation (see Chapter 4). This transfer is mediated
primarily by plasmids, but some transposons, called conjugative transposons, are capable of transferring antibiotic resistance as well.

In contrast to plasmids or bacterial viruses, transposons are not capable of independent replication; they replicate as part of the DNA in which they are
integrated. More than one transposon can be located in the DNA; for example, a plasmid can contain several transposons carrying drug­resistant
genes. Insertion sequences are a type of transposon that have fewer bases (800–1500 base pairs), since they do not code for their own integration
enzymes. They can cause mutations at their site of integration and can be found in multiple copies at the ends of larger transposon units.

Structures Outside the Cell Wall

Capsule

The capsule is a gelatinous layer covering the entire bacterium. It is typically composed of polysaccharide. The sugar components of the
polysaccharide vary from one species of bacteria to another and frequently determine the serologic type (serotype) within a species. For example,
The capsule is a gelatinous layer covering the entire bacterium. It is typically composed of polysaccharide. The sugar components of the
polysaccharide vary from one species of bacteria to another and frequently determine the serologic type (serotype) within a species. For example,
there are approximately 95 different serotypes of Streptococcus pneumoniae, which are distinguished by the antigenic differences of the sugars in the
polysaccharide capsule.

The capsule is important for four reasons:

1. It is a determinant of virulence of many bacteria since it limits the ability of phagocytes to engulf the bacteria. Variants of encapsulated bacteria that
have lost the ability to produce a capsule are usually nonpathogenic.

2. Specific identification of an organism can be made by using antiserum against the capsular polysaccharide. In the presence of the homologous
antibody, the capsule will swell greatly. This swelling phenomenon, which is used in the clinical laboratory to identify certain organisms, is called
the Quellung reaction.

3. Capsular polysaccharides are used as antigens in certain vaccines because they are capable of eliciting protective antibodies. For example, the
capsular polysaccharide of S. pneumoniae, Neisseria meningitidis, and Haemophilus influenzae is the immunogen in the current vaccine against
these bacteria.

4. The capsule may play a role in the adherence of bacteria to human tissues, which is an important initial step in causing infection.

Flagella

Flagella are long, whip­like appendages that move the bacteria toward nutrients and other attractants, a process called chemotaxis. The long
filament, which acts as a propeller, is composed of many subunits of a single protein, flagellin, arranged in several intertwined chains.

Flagellated bacteria have a characteristic number and location of flagella: some bacteria have one, and others have many; in some, the flagella are
located at one end, and in others, they are all over the outer surface. Only certain bacteria have flagella. Many rods do, but most cocci do not and are
therefore nonmotile. Spirochetes move by using a flagellum­like structure called the axial filament, which wraps around the spiral­shaped cell to
produce an undulating motion.

Flagella are medically important for two reasons:

1. Some species of motile bacteria (e.g., E. coli and Proteus species) are common causes of urinary tract infections. Flagella may play a role in
pathogenesis by propelling the bacteria up the urethra into the bladder.

2. Some species of bacteria (e.g., Salmonella species) are identified in the clinical laboratory by the use of specific antibodies against flagellar
proteins.

Pili (Fimbriae)

Pili are hairlike filaments that extend from the cell surface. They are shorter and straighter than flagella and are composed of subunits of pilin, a
protein arranged in helical strands. They are found mainly on gram­negative organisms.

Pili have two important roles:

1. They mediate the attachment of bacteria to specific receptors on the human cell surface, which is a necessary step in the initiation of infection for
some organisms. Mutants of Neisseria gonorrhoeae that do not form pili are nonpathogens.

2. A specialized kind of pilus, the sex pilus, forms the attachment between the donor and the recipient bacteria during conjugation (see Chapter 4).

Glycocalyx (Slime Layer)

The glycocalyx is a polysaccharide coating that is secreted by many bacteria. It covers surfaces like a film and allows the bacteria to adhere firmly to
various structures (e.g., skin, heart valves, prosthetic joints, and catheters). The glycocalyx is an important component of biofilms (see Chapter 7). The
medical importance of the glycocalyx is illustrated by the finding that it is the glycocalyx­producing strains of P. aeruginosa that cause respiratory tract
infections in cystic fibrosis patients, and it is the glycocalyx­producing strains of Staphylococcus epidermidis and viridans streptococci that cause
medical importance of the glycocalyx is illustrated by the finding that it is the glycocalyx­producing strains of P. aeruginosa that cause respiratory tract
infections in cystic fibrosis patients, and it is the glycocalyx­producing strains of Staphylococcus epidermidis and viridans streptococci that cause
endocarditis. The glycocalyx also mediates adherence of certain bacteria to the surface of teeth. This plays an important role in the formation of
plaque.

Bacterial Spores

These highly resistant structures are formed in response to adverse conditions by two genera of medically important gram­positive rods: the genus
Bacillus, which includes the agent of anthrax, and the genus Clostridium, which includes the agents of tetanus and botulism. Spore formation
(sporulation) occurs when nutrients, such as sources of carbon and nitrogen, are depleted (Figure 2–8). The spore forms inside the cell and contains
bacterial DNA, a small amount of cytoplasm, cell membrane, peptidoglycan, very little water, and most importantly, a thick, keratin­like coat that is
responsible for the remarkable resistance of the spore to heat, dehydration, radiation, and chemicals. This resistance may be mediated by dipicolinic
acid, a calcium ion chelator found only in spores.

FIGURE 2–8

Bacterial spores. The spore contains the entire DNA genome of the bacterium surrounded by a thick, resistant coat.

Once formed, the spore has no metabolic activity and can remain dormant for many years. Upon exposure to water and the appropriate nutrients,
specific enzymes degrade the coat, water and nutrients enter, and germination into a potentially pathogenic bacterial cell occurs. Note that this
differentiation process is not a means of reproduction since one cell produces one spore that germinates into one cell.

The medical importance of spores lies in their extraordinary resistance to heat and chemicals. As a result of their resistance to heat, sterilization
cannot be achieved by boiling. Steam heating under pressure (autoclaving) at 121°C, for at least 15 minutes, is required to ensure the sterility of
products for medical use. Spores are often not seen in clinical specimens recovered from patients infected by spore­forming organisms because the
supply of nutrients is adequate.

Table 2–4 describes the medically important features of bacterial spores.

TABLE 2–4
Important Features of Spores and Their Medical Implications

Important Features of Spores Medical Implications

Highly resistant to heating; spores are not killed by boiling (100°C), but Medical supplies must be heated to 121°C for at least 15 minutes to be
are killed at 121°C. sterilized.

Highly resistant to many chemicals, including most disinfectants, due to Only solutions designated as sporicidal will kill spores.
the thick, keratin­like coat of the spore.

They can survive for many years, especially in the soil. Wounds contaminated with soil can be infected with spores and cause
diseases such as tetanus (C. tetani) and gas gangrene (C. perfringens).

They exhibit no measurable metabolic activity. Antibiotics are ineffective against spores because antibiotics act by inhibiting
certain metabolic pathways of bacteria. Also, spore coat is impermeable to
antibiotics.

Spores form when nutrients are insufficient but then germinate to form Spores are not often found at the site of infections because nutrients are not
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