27.1 Overview of Human–Microbial Interactions Most microorganisms are benign –Few contribute to...

27.1 Overview of Human–Microbial 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

© 2012 Pearson Education, Inc.


• 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© 2012 Pearson Education, Inc.


• 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


27.2 Normal Microflora of the Skin

• The skin is generally a dry, acid environment that does not support the growth of most microorganisms (Figure 27.2)

• Moist areas (e.g., sweat glands) are readily colonized by gram-positive bacteria and other normal flora of the skin– Composition is influenced by

• Environmental factors (e.g., weather) • Host factors (e.g., age, personal hygiene)


27.3 Normal 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 27.4)


Figure 27.4

Enamel

Dentin

Gingival crevice

Pulp

Gingiva

Alveolar bone

Periodontalmembrane

Bonemarrow

Crown

Root


Figure 27.5



• Extensive growth of oral microorganisms, especially streptococci, results in a thick bacterial layer (dental plaque)

• As plaque continues to develop, anaerobic bacterial species begin to grow


Figure 27.6

Day 1 1436 mm2

Day 10 22,522 mm2


Figure 27.7



• As dental plaque accumulates, the microorganisms produce high concentrations of acid that results in decalcification of the tooth enamel (dental caries)

• The lactic acid bacteria Streptococcus sobrinus and Streptococcus mutans are common agents in dental caries (Figure 27.8)


27.4 Normal Microflora of the Gastrointestinal Tract

• The human gastrointestinal (GI) tract– 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


Figure 27.9

Major bacteria present Organ

Esophagus

Stomach

Smallintestine

Largeintestine

pH 2

Secretion of acid (HCl)Digestion of macromolecules

pH 4–5

Continued digestionAbsorption of monosaccharides,amino acids, fatty acids, water

pH 7

Absorption of bile acids,vitamin B12

Duodenum

Jejunum

Ileum

Colon

Anus

Esophagus

LactobacilliEnterococci

PrevotellaStreptococcusVeillonella

HelicobacterProteobacteriaBacteroidetesActinobacteriaFusobacteria

BacteroidesBifidobacteriumClostridiumEnterobacteriaEnterococcusEscherichiaEubacteriumKlebsiellaLactobacillusMethanobrevibacter (Archaea)PeptococcusPeptostreptococcusProteusRuminococcusStaphylococcusStreptococcus

Major physiologicalprocesses


27.4 Normal 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 is influenced by the composition of the intestinal flora and the diet

• Compounds produced include:– Vitamins

– Gas, organic acids, and odor

– Enzymes


27.5 Normal Microflora of Other Body Regions

• A restricted group of organisms colonizes the upper respiratory tract– Examples: staphylococci, streptococci,

diphtheroid bacilli, and gram-negative cocci

• The lower respiratory tract lacks microflora in healthy individuals


Figure 27.11

Sinuses

Nasopharynx

Pharynx

Oral cavity

Larynx

Trachea

Bronchi

Lungs

Upperrespiratorytract

Lowerrespiratorytract



• Urogenital Tract– 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



• 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

– Lactic acid maintains a local acidic environment


27.6 Measuring Virulence

• Pathogens use various strategies to establish virulence (Figure 27.13)

• Virulence is the relative ability of a pathogen to cause disease



• 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

– 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


Figure 27.14

Number of cells injected per mouse

101 102 103 104 105 106 107

100

80

60

40

20

Pe

rce

nta

ge

of

mic

e k

ille

d

Highly virulentorganism(Streptococcuspneumoniae)

Moderately virulentorganism(Salmonella entericaserovar Typhimurium)



• 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


Figure 27.13

EXPOSUREto pathogens

ADHERENCEto skin or mucosa

INVASIONthrough epithelium

COLONIZATIONand

GROWTHProduction of

virulence factors

TOXICITY:toxin effects arelocal or systemic

INVASIVENESS:further growth atoriginal and distant sites

TISSUEDAMAGE,DISEASE

Further exposure

Further exposure at local sites


27.7 Entry of the Pathogen into the Host – Adherence

• Specific Adherence– A pathogen must usually gain access to host

tissues and multiply before damage can be done

– Bacteria and viruses that initiate infection often adhere specifically to epithelial cells through macromolecular interactions on the surfaces of the pathogen and the host cell (Figure 27.15)


Figure 27.15



• Bacterial adherence can be facilitated by – Extracellular macromolecules that are not

covalently attached to the bacterial cell surface• Examples: slime layer, capsule

– Fimbriae and pili


Figure 27.16


Figure 27.18



• 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



• Pathogen Invasion– Starts at the site of adherence

– May spread throughout the host via the circulatory or lymphatic systems


27.8 Colonization and Infection

• 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


27.9 Invasion

• 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


27.10 Exotoxins

• Exotoxins– Proteins released from the pathogen cell as it

grows

– Three categories:• Cytolytic toxins• AB toxins• Superantigen toxins


27.10 Exotoxins

• Cytolytic toxins– Work by degrading cytoplasmic membrane

integrity, causing cell lysis and death• Toxins that lyse red blood cells are called

hemolysins (Figure 27.19)• Staphylococcal -toxin kills nucleated cells and

lyses erythrocytes (Figure 27.20)


Figure 27.19


Figure 27.20

Cytoplasmicmembrane

-Toxin pore

Out

InInflux of extracellularcomponents

Efflux ofcytoplasmiccomponents


27.10 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 27.21)

• Examples: diphtheria toxin, tetanus toxin, botulinum toxin


Animation: Diphtheria and Cholera ToxinsAnimation: Diphtheria and Cholera Toxins

Figure 27.21

Cytoplasmicmembrane

Diphtheria toxinAmino acid

Ribosome

Diphtheria toxin

Receptorprotein

Out

In

Normal protein synthesis Protein synthesis stops


27.10 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 27.22); tetanus toxin is also an AB protein neurotoxin (Figure 27.23)


Figure 27.22

Excitation signalsfrom the centralnervous system

Muscle

NormalAcetylcholine (A) inducescontraction of muscle fibers

BotulismBotulinum toxin, , blocksrelease of A, inhibiting contraction


Figure 27.23

Inhibitoryinterneuron

Inhibition

Excitation signalsfrom the centralnervous system

Tetanustoxin

Muscle

NormalGlycine (G) release from inhibitoryinterneurons stops acetylcholine(A) release and allows relaxationof muscle

TetanusTetanus toxin binds to inhibitoryinterneurons, preventing releaseof glycine (G) and relaxationof muscle


27.10 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 27.24)


Figure 27.24

Blood Intestinalepithelialcells

GM1

Lumen ofsmall intestine

Normal ion movement, Na from lumen to blood,no net Cl movement

Colonization and toxin production by V. cholerae

Activation of epithelial adenylate cyclase by cholera toxin

Na movement blocked, net Cl movement to lumen

Massive water movement to the lumen; cholera symptoms

CholeratoxinAB form

Vibriocholeraecell

GM1

A subunits

Adenylate cyclase

ATP Cyclic AMP

Choleratoxin Bsubunit


27.11 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

– The presence of endotoxin can be detected by the Limulus amoebocyte lysate (LAL) assay (Figure 27.25)


Figure 27.25


27.1 Overview of Human–Microbial Interactions Most microorganisms are benign –Few contribute to...

Documents

Transcript of 27.1 Overview of Human–Microbial Interactions Most microorganisms are benign –Few contribute to...