PowerPoint Lecture

Presentations prepared by
John Zamora
Middle Tennessee State
University

CHAPTER 23
Microbial
Interactions
with Humans

Pearson Education Limited 2015

 I. Normal Human-Microbial Interactions

23.1 Beneficial HumanMicrobial Interactions

23.2 Microflora of the Skin

23.3 Microflora of the Oral Cavity

23.4 Microflora of the Gastrointestinal Tract

23.5 Microflora of Mucosal Tissues

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 23.1 Beneficial HumanMicrobial Interactions

Most microorganisms are benign

Few contribute to health, and fewer pose direct threats
to health

Normal microbial flora

Microorganisms usually found associated with human
body tissue

Humans are colonized by microorganisms at birth

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 23.1 Beneficial HumanMicrobial Interactions

Pathogens
Microbial parasites

Pathogenicity
The ability of a parasite to inflict damage on the host

Virulence
Measure of pathogenicity

Opportunistic pathogen
Causes disease only in the absence of normal host
resistance
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 23.1 Beneficial HumanMicrobial Interactions

Infection
Situation in which a microorganism is established and
growing in a host, whether or not the host is harmed

Disease
Damage or injury to the host that impairs host function

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 23.1 Beneficial HumanMicrobial Interactions

Animals provide a favorable environment for the

growth of many microorganisms

Infections frequently begin at sites in the animal's

mucous membranes (Figure 23.1)

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 Mucus Colonization
Microbial
cells

Epithelial
cell

2015 Pearson Education, Inc. Figure 23.1

 23.2 Microflora of the Skin

The skin surface varies greatly in chemical composition

and moisture content
Three microenvironments
Dry skin
Moist skin
Sebaceous skin

Skin microflora examined by molecular ecology methods

19 phyla detected
Each microenvironment shows a unique microbiota
(Figure 23.2)
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 Others 1%
Bacteroidetes
6.3%

Gram
negative

Proteobacteria
16.5%
Actinobacteria
51.8%
Other
Firmicutes Flavobacteriales
24.4%
Betaproteobacteria
Gram Corynebacteria
positive Staphylococci
Propionibacteria

2015 Pearson Education, Inc. Figure 23.2

 23.2 Microflora of the Skin

The skin microflora

Composition is influenced by:
Environmental factors (e.g., weather)

Host factors (e.g., age, personal hygiene)

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 23.3 Microflora of the Oral Cavity

The oral cavity is a complex, heterogeneous

microbial habitat

Saliva contains antimicrobial enzymes

But high concentrations of nutrients near surfaces in the
mouth promote localized microbial growth

The tooth consists of a mineral matrix (enamel)

surrounding living tissue (dentin and pulp;
Figure 23.3)
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 Enamel

Dentin
Crown
Gingival crevice

Pulp

Gingiva

Alveolar bone

Periodontal
membrane Root

Bone
marrow

2015 Pearson Education, Inc. Figure 23.3

 23.3 Microflora of the Oral Cavity

Bacteria colonize tooth surfaces by first attaching

to acidic glycoproteins deposited there by saliva
(Figure 23.4)

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 2015 Pearson Education, Inc. Figure 23.4
 23.3 Normal Microflora of the Oral Cavity

Metagenomic analysis of human microflora shows

a complex microbial community
Most microorganisms are facultatively aerobic

Some are obligately anaerobic

Some are obligately aerobic

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 23.4 Microflora of the Gastrointestinal Tract

The human gastrointestinal (GI) tract (Figure 23.5)

Consists of stomach, small intestine, and large intestine

Responsible for digestion of food, absorption of

nutrients, and production of nutrients by the indigenous
microbial flora

Contains 1013 to 1014 microbial cells

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 Esophagus
Major bacteria present Organ Major physiological processes

Prevotella Esophagus
Streptococcus
Veillonella
Helicobacter Secretion of acid (HCI)
Stomach Digestion of macromolecules
Proteobacteria
Bacteroidetes pH 2
Actinobacteria
Fusobacteria
Duodenum

Enterococci Continued digestion

Lactobacilli Jejunum Small Absorption of monosaccharides,
intestine amino acids, fatty acids, water
Bacteroides pH 45
Bifidobacterium
Clostridium IIeum
Enterobacteria
Enterococcus
Escherichia
Eubacterium Absorption of bile acids,
Colon Large
Klebsiella vitamin B12
intestine
Lactobacillus pH 7
Methanobrevibacter
(Archaea)
Peptococcus
Peptostreptococcus
Proteus
Ruminococcus Anus
Staphylococcus
Streptococcus

2015 Pearson Education, Inc. Figure 23.5

 23.4 Microflora of the Gastrointestinal Tract

Microbial populations in different areas of the GI

tract are influenced by diet and the physical
conditions in the area

The acidity of the stomach and the duodenum of

the small intestine (~pH 2) prevents many
organisms from colonizing the GI tract

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 23.4 Microflora of the Gastrointestinal Tract

Functions and products of intestinal flora

Intestinal microorganisms carry out a variety of essential
metabolic reactions that produce various compounds
The type and amount produced are influenced by the
composition of the intestinal flora and the diet

Compounds produced include:

Vitamins

Gas, organic acids, and odor

Enzymes
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 23.5 Microflora of Mucosal Tissues

A restricted group of organisms colonizes the

upper respiratory tract (Figure 23.7)
Examples: staphylococci, streptococci, diphtheroid
bacilli, and gram-negative cocci

The lower respiratory tract lacks microflora in

healthy individuals

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 Sinuses
Nasopharynx
Upper
respiratory Pharynx
tract
Oral cavity
Larynx

Trachea
Lower
respiratory Bronchi
tract
Lungs

2015 Pearson Education, Inc. Figure 23.7

 23.5 Microflora of Mucosal Tissues

Urogenital tract (Figure 23.8a)

The bladder is typically sterile in both males and
females

Altered conditions (such as change in pH) can cause

potential pathogens in the urethra (such as Escherichia
coli and Proteus mirabilis) to multiply and become
pathogenic
E. coli and P. mirabilis frequently cause urinary tract
infections in women
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 Female Male

Bladder
Ovary

Uterus
Cervix Prostate

Bladder
Pubis Rectum

Urethra
Pubis

Rectum

Urethra
Penis

Vagina Testis

2015 Pearson Education, Inc. Figure 23.8a

 23.5 Microflora of Mucosal Tissues

The vagina of the adult female is weakly acidic

and contains significant amounts of glycogen
Lactobacillus acidophilus, a resident organism in the
vagina, ferments the glycogen, producing lactic acid
(Figure 23.8b)

Lactic acid maintains a local acidic environment

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 2015 Pearson Education, Inc. Figure 23.8b
 II. Pathogenesis

23.6 Pathogenicity and Virulence

23.7 Adherence

23.8 Invasion, Infection, and Virulence Factors

23.9 Exotoxins

23.10 Endotoxins

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 23.6 Pathogenicity and Virulence

Pathogens use various strategies to establish

virulence (Figure 23.9)

Virulence is the relative ability of a pathogen to

cause disease

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 2015 Pearson Education, Inc. Figure 23.9
 23.6 Pathogenicity and Virulence

Measuring virulence
Virulence can be estimated from experimental studies of
the LD50 (lethal dose50)
The amount of an agent that kills 50% of the animals in a
test group (Figure 23.10)

Highly virulent pathogens show little difference in the

number of cells required to kill 100% of the population
as compared to 50% of the population

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 2015 Pearson Education, Inc. Figure 23.10
 23.6 Pathogenicity and Virulence

Attenuation
The decrease or loss of virulence

Toxicity
Organism causes disease by means of a toxin that
inhibits host cell function or kills host cells
Toxins can travel to sites within host not inhabited by
pathogen

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 23.6 Pathogenicity and Virulence

Invasiveness
Ability of a pathogen to grow in host tissue at densities
that inhibit host function
Can cause damage without producing a toxin

Many pathogens use a combination of toxins,

invasiveness, and other virulence factors to
enhance pathogenicity

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 23.7 Adherence

Bacteria and viruses that initiate infection often

adhere specifically to epithelial cells through
interactions between molecules on the surfaces of
the pathogen and the host cell (Figure 23.12)

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 2015 Pearson Education, Inc. Figure 23.12
 23.7 Adherence

Bacterial adherence can be facilitated by

Extracellular macromolecules that are not covalently
attached to the bacterial cell surface
Examples: slime layer, capsule (Figure 23.13)

Fimbriae and pili (Figure 23.14)

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 2015 Pearson Education, Inc. Figure 23.13
 2015 Pearson Education, Inc. Figure 23.14
 23.8 Invasion, Infection, and Virulence Factors

The initial inoculum of a pathogen is insufficient to

cause host damage

The pathogen must multiply and colonize the

tissue

The availability of nutrients is most important in

affecting pathogen growth

Pathogens may grow locally at the site of invasion

or may spread throughout the body
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 23.8 Invasion, Infection, and Virulence Factors

Bacteremia: the presence of bacteria in the

bloodstream

Septicemia: bloodborne systemic infection

May lead to massive inflammation, septic shock, and
death

Infection: any situation in which a microorganism

(not a member of the local flora) is established and
growing in a host
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 23.8 Invasion, Infection, and Virulence Factors

Infection requires attachment to surface as well as

growth

Attachment and growth have been well studied in

the formation of biofilms on tooth surfaces
Acidic glycoproteins from saliva form a thin film

Streptococci colonize the film

Streptococcus sobrinus and Streptococcus mutans are
common agents in tooth decay (Figure 23.15)

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 Dextran

Cells

2015 Pearson Education, Inc. Figure 23.15

 23.8 Invasion, Infection, and Virulence Factors

Extensive growth of oral microorganisms, especially

streptococci, results in a thick bacterial layer (dental
plaque; Figure 23.16)

As plaque continues to develop, anaerobic bacterial

species begin to grow

As dental plaque accumulates, the microorganisms

produce high concentrations of acid, resulting in
decalcification of the tooth enamel (dental caries)

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 2015 Pearson Education, Inc. Figure 23.16
 23.8 Invasion, Infection, and Virulence Factors

Pathogens produce enzymes that:

Enhance virulence by breaking down or altering host
tissue to provide access to nutrients
Example: hyaluronidase

Protect the pathogen by interfering with normal host

defense mechanisms
Example: coagulase

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 23.8 Invasion, Infection, and Virulence Factors

Salmonella species encode a large number of

virulence factors (Figure 23.17)
Several genes that direct invasion are clustered
together on the chromosome as pathogenicity islands

Another Salmonella pathogenicity island contains genes

that promote a more systemic disease

Salmonella also contains resistance plasmids (R

plasmids)

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 Enterotoxin
(diarrhea) Siderophores
Injectisome (iron uptake)
(inv and prg
products form Type fimbriae
complex) (adherence)

Endotoxin in
LPS layer Virulence
plasmid
(fever) SP2
SP1
Anti-
phagocytic
proteins
induced Cytotoxin
by oxyR (inhibits host cell protein
synthesis; Ca2+ efflux
O antigen from host cell; adherence)
(inhibits Vi capsule antigen;
phagocyte inhibits complement binding
killing) Pathogenicity
islands on Flagellum (motility)
chromosome H antigen (adherence;
inhibits phagocyte killing)

2015 Pearson Education, Inc. Figure 23.17

 23.9 Exotoxins

Exotoxins
Proteins released from the pathogen cell as it grows

Three categories
Cytotoxins

AB toxins

Superantigen toxins

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 23.9 Exotoxins

Cytotoxins (cytolytic toxins)

Work by degrading cytoplasmic membrane integrity,
causing cell lysis and death
Toxins that lyse red blood cells are called hemolysins
(Figure 23.18)

Staphylococcal -toxin kills nucleated cells and lyses

erythrocytes (Figure 23.19)

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 2015 Pearson Education, Inc. Figure 23.18
 RCSB PDB 3ANZ
Efflux of
cytoplasmic
components
Out

Cytoplasmic In
membrane -Toxin pore

Influx of
extracellular
components

2015 Pearson Education, Inc. Figure 23.19

 23.9 Exotoxins

AB toxins
Consist of two subunits, A and B

Work by binding to host cell receptor (B subunit) and

transferring damaging agent (A subunit) across the cell
membrane (Figure 23.20)
Examples: diphtheria toxin, tetanus toxin, botulinum toxin

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 Cytoplasmic membrane Diphtheria toxin Out
A B A B

A Receptor protein In
A
EF-2 EF-2*

Amino
acid
A T
A T G

Ribosome

Normal protein synthesis Protein synthesis stops

2015 Pearson Education, Inc. Figure 23.20

 Diphtheria and Cholera Toxins

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 23.9 Exotoxins

Clostridium tetani and Clostridium botulinum

produce potent AB exotoxins that affect nervous
tissue

Botulinum toxin consists of several related AB

toxins that are the most potent biological toxins
known (Figure 23.21); tetanus toxin is also an AB
protein neurotoxin (Figure 23.22)

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 Excitation signals
from the central
nervous system

A A AA AA AA A
AA AA A A AA A A A AA
A A A A
A A
A A A A A A A
A
A A A
A A
Muscle

Normal Botulism
Acetylcholine (A) induces contraction Botulinum toxin, , blocks release of A,
of muscle fibers inhibiting contraction

2015 Pearson Education, Inc. Figure 23.21

 Inhibitory
GG
interneuron G
GG G G
GG
G GG G
Inhibition GG
G GG
GG
GG Excitation signals
G from the central Tetanus
nervous system toxin

A AA
AA AA AA A AA
A A AA AA AA
A A A A A
A A A
A
A A A A
A A A A
A A A

Muscle

Normal Tetanus
Glycine (G) release from inhibitory interneurons Tetanus toxin binds to inhibitory interneurons,
stops acetylcholine (A) release and allows preventing release of glycine (G) and relaxation
relaxation of muscle of muscle

2015 Pearson Education, Inc. Figure 23.22

 23.9 Exotoxins

Enterotoxins
Exotoxins whose activity affects the small intestine

Generally cause massive secretion of fluid into the

intestinal lumen, resulting in vomiting and diarrhea
Example: cholera toxin (Figure 23.23)

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 1. Normal ion movement, Na+ from lumen to blood, 4. Na+ movement blocked, net Cl movement to lumen
no net Cl movement

Blood Intestinal Lumen of

epithelial small intestine
cells
GM1

5. Massive water movement to the lumen; cholera symptoms

2. Infection and toxin production by V. cholerae

Cholera
toxin
AB form
GM1
Vibrio
cholerae
B A cell

3. Activation of epithelial adenylate cyclase by cholera toxin

A subunits
Cholera
toxin B
Adenylate cyclase subunit

ATP Cyclic
AMP

2015 Pearson Education, Inc. Figure 23.23

 23.10 Endotoxins

Endotoxin
The lipopolysaccharide portion of the cell envelope of
certain gram-negative Bacteria, which is a toxin when
solubilized

Generally less toxic than exotoxins

Presence of endotoxin can be detected by the Limulus

amoebocyte lysate (LAL) assay (Figure 23.24)

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 2015 Pearson Education, Inc. Figure 23.24
 III. Host Factors in Infection and Disease

23.11 Innate Resistance to Infection

23.12 Risk Factors for Infection

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 23.11 Innate Resistance to Infection

Hosts have innate resistance to most pathogens

(Figure 23.25)
Natural host resistance

Tissue specificity

Physical and chemical barriers

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 Lysozyme in
tears and other
secretions
dissolves cell
Removal of particles
walls
including microorganisms Mucus and cilia
by cilia in nasopharynx lining trachea
suspend and
move micro-
Skin is a physical organisms out of
barrier and produces the body
antimicrobial fatty Mucus,
acids and anti- antibacterial
bacterial peptides. peptides, and
Normal flora phagocytes in
inhibit infection lungs prevent
infection
Stomach acidity
Blood and
(pH 2) inhibits lymph
microbial growth proteins inhibit
microbial
growth

Normal flora Rapid pH

compete with change
pathogens in inhibits
the gut and microbial
on the skin growth

Epithelial
cells
throughout
the body
have tight
junctions
that
Flushing of urinary inhibit
tract prevents pathogen
infection invasion and
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infection
Figure 23.25
 23.12 Risk Factors for Infection

Compromised host
One or more resistance mechanisms are inactive

The probability of infection is increased

Age is an important factor

Very young and very old individuals are more susceptible

Stress can predispose a healthy individual to disease

Diet plays a role in host susceptibility to infection

Certain genetic conditions can compromise a host

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