Lippincotts_Illustrated_Reviews_Microbiology_3rd_Edition_by_Richard_A _Harvey_Cynthia_Nau_Cornelissen_Ph D
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Lippincotts_Illustrated_Reviews_Microbiology_3rd_Edition_by_Richard_A _Harvey_Cynthia_Nau_Cornelissen_Ph D

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in which strains that
lack pili are not pathogenic (see p. 101).
3. Invasiveness: Invasive bacteria are those that can enter host cells
or penetrate mucosal surfaces, spreading from the initial site of
infection. Invasiveness is facilitated by several bacterial enzymes,
the most notable of which are collagenase and hyaluronidase.
These enzymes degrade components of the extracellular matrix,
providing the bacteria with easier access to host cell surfaces.
Many bacterial pathogens express membrane proteins known as
"invasins" that interact with host cell receptors, thereby eliciting
signaling cascades that result in bacterial uptake by induced
phagocytosis. Invasion is followed by inflammation, which can be
either pyogenic (involving pus formation) or granulomatous
12 3. Pathogenicity Of Microorganisms
Toxin ADP-ribosylates host protein 
elongation factor, stopping protein 
Toxin ADP-ribosylates a G protein of 
intestinal mucosal cells, resulting in ionic 
imbalance and loss of water.
Toxin cleaves a protein 
involved in release 
of neurotransmitters.
Figure 3.3
Action of exotoxins. ADP = adenosine 
diphosphate; ADPR = adenosine 
diphosphate ribose; NAD+ = nicotin-
amide adenine dinucleotide.
A+ N
The membrane recognition 
portion of the toxin (B) binds 
to the cell membrane.
Cell membrane
for toxin
Diphtheria toxin
Active subunit 
of toxin
e subunit 
of toxin
of tox
After entering the cell, the A subunit 
dissociates and cleaves or modifies
a target molecule within the cell.
EF-2 EF-2
G Protein
Amino acids Protein
G Protein ADPR
Toxin cleaves host ribosomal RNA, resulting 
in inhibition of protein synthesis. 
II. Bacterial Pathogenesis 13
 (having nodular inflammatory lesions), depending on the organ-
ism. The pus of pyogenic inflammations contains mostly neu-
trophils, whereas granulomatous lesions contain fibroblasts,
lymphocytes, and macrophages. 
4. Iron sequestering: Iron is an essential nutrient for most bacteria.
To obtain the iron required for growth, bacteria produce iron-bind-
ing compounds, called siderophores. These compounds capture
iron from the host by chelation, and then the ferrated siderophore
binds to specific receptors on the bacterial surface. Iron is actively
transported into the bacterium, where it is incorporated into
essential compounds such as cytochromes. The pathogenic
Neisseria species are exceptions in that they do not produce
siderophores but instead utilize host iron-binding proteins, such
as transferrin and lactoferrin, as iron sources. They do so by
expressing dedicated receptors that bind to these host proteins
and remove the iron for internalization.
5. Virulence factors that inhibit phagocytosis: The most important
antiphagocytic structure is the capsule external to the cell wall,
such as in S. pneumoniae and N. meningitidis. A second group of
antiphagocytic factors are the cell wall proteins of gram-positive
cocci, such as protein A of staphylococcus and M protein of group
A streptococci (see pp. 70, 80).
6. Bacterial toxins: Some bacteria cause disease by producing toxic
substances, of which there are two general types: exotoxins and
endotoxin. Exotoxins, which are proteins, are secreted by both
gram-positive and gram-negative bacteria. In contrast, endotoxin,
which is synonymous with lipopolysaccharide (LPS), is not
secreted but instead is an integral component of the cell walls of
gram-negative bacteria.
a. Exotoxins: These include some of the most poisonous sub-
stances known. It is estimated that as little as 1 \u3bcg of tetanus
exotoxin can kill an adult human. Exotoxin proteins generally
have two polypeptide components (Figure 3.3). One is responsi-
ble for binding the protein to the host cell, and one is responsible
for the toxic effect. In several cases, the precise target for the
toxin has been identified. For example, diphtheria toxin is an
enzyme that blocks protein synthesis. It does so by attaching an
adenosine diphosphate\u2013ribosyl group to human protein elonga-
tion factor EF-2, thereby inactivating it (see p. 92). Most exotox-
ins are rapidly inactivated by moderate heating (60o C), notable
exceptions being staphylococcal enterotoxin and E. coli heat-
stable toxin (ST). In addition, treatment with dilute formaldehyde
destroys the toxic activity of most exotoxins but does not affect
their antigenicity. Formaldehyde-inactivated toxins, called tox-
oids, are useful in preparing vaccines (see p. 36). Exotoxin pro-
teins are, in many cases, encoded by genes carried on plasmids
or temperate bacteriophages. An example is the diphtheria exo-
toxin that is encoded by the tox gene of a temperate bacterio-
phage that can lysogenize Corynebacterium diphtheriae. Strains
of C. diphtheriae that carry this phage are pathogenic, whereas
those that lack the phage are nonpathogenic.
14 3. Pathogenicity Of Microorganisms
b. Endotoxins: These are heat-stable, LPS components of the
outer membranes of gram-negative (but not gram-positive) bac-
teria. They are released into the host\u2019s circulation following bac-
terial cell lysis. LPS consists of polysaccharide composed of
repeating sugar subunits (O antigen), which protrudes from the
exterior cell surface; a core polysaccharide; and a lipid compo-
nent called lipid A that is integrated into the outer leaflet of the
outer membrane. The lipid A moiety is responsible for the toxic-
ity of this molecule. The main physiologic effects of LPS endo-
toxin are fever, shock, hypotension, and thrombosis, collectively
referred to as septic shock. These effects are produced indi-
rectly by macrophage activation, with the release of cytokines,
activation of complement, and activation of the coagulation cas-
cade. Death can result from multiple organ failure. Elimination
of the causative bacteria with antibiotics can initially exacer-
bate the symptoms by causing sudden massive release of
endotoxin into the circulation. Although gram-positive bacteria
do not contain LPS, their cell wall peptidoglycan and teichoic
acids can elicit a shock syndrome similar to that caused by LPS
but usually not as severe. 
B. Host-mediated pathogenesis 
The pathogenesis of many bacterial infections is caused by the host
response rather than by bacterial factors. Classic examples of host
response\u2013mediated pathogenesis are seen in diseases such as
gram-negative bacterial sepsis, tuberculosis, and tuberculoid
 leprosy. The tissue damage in these infections is caused by various
cytokines released from the lymphocytes, macrophages, and poly-
morphonuclear leukocytes at the site of infection or in the blood-
stream. Often the host response is so intense that host tissues are
destroyed, allowing remaining bacteria to proliferate.
C. Antigenic variation
A successful pathogen must evade the host\u2019s immune system that
recognizes bacterial surface antigens. One important evasive strat-
egy for the pathogen is to change its surface antigens. This is
accomplished by several mechanisms. One mechanism, called
phase variation, is the genetically reversible ability of certain bacteria
to turn off and turn on the expression of genes coding for surface
antigens. A second mechanism, called antigenic variation, involves
the modification of the gene for an expressed surface antigen by
genetic recombination with one of many variable unexpressed DNA
sequences. In this manner, the expressed surface antigen can
assume many different antigenic structures (see Figure 11.3).
D. Which is the pathogen? 
Isolating a particular microorganism from infected tissue (for exam-
ple, a necrotic skin lesion), does not conclusively demonstrate that it
caused the lesion. The organism could, for example, be a harmless
member of the normal skin flora (see p. 7) that happened to be in
the vicinity. Alternatively,