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.

27.1 Overview of Human–Microbial 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 © 2012 Pearson Education, Inc.

27.1 Overview of Human–Microbial 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 © 2012 Pearson Education, Inc.

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) © 2012 Pearson Education, Inc.

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) © 2012 Pearson Education, Inc.

Crown Root Enamel Dentin Gingival crevice Pulp Gingiva Alveolar bone Figure 27.4 Enamel Dentin Crown Gingival crevice Pulp Gingiva Alveolar bone Periodontal membrane Root Figure 27.4 Section through a tooth. Bone marrow © 2012 Pearson Education, Inc.

Figure 27.5 Figure 27.5 Microcolonies of bacteria. © 2012 Pearson Education, Inc.

27.3 Normal Microflora of the Oral Cavity 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 © 2012 Pearson Education, Inc.

Figure 27.6 Day 1 1436 mm2 Day 10 22,522 mm2 Figure 27.6 Distribution of dental plaque. © 2012 Pearson Education, Inc.

Figure 27.7 Figure 27.7 Dental plaque. © 2012 Pearson Education, Inc.

27.3 Normal Microflora of the Oral Cavity 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) © 2012 Pearson Education, Inc.

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 © 2012 Pearson Education, Inc.

Major bacteria present Organ Major physiological processes Figure 27.9 Esophagus Major bacteria present Organ Major physiological processes Prevotella Esophagus Streptococcus Veillonella Helicobacter pH 2 Secretion of acid (HCl) Digestion of macromolecules Stomach Proteobacteria Bacteroidetes Actinobacteria Fusobacteria Duodenum Enterococci pH 4–5 Continued digestion Absorption of monosaccharides, amino acids, fatty acids, water Lactobacilli Small intestine Jejunum Bacteroides Bifidobacterium Clostridium Ileum Enterobacteria Enterococcus Escherichia Figure 27.9 The human gastrointestinal tract. Eubacterium Large intestine pH 7 Absorption of bile acids, vitamin B12 Klebsiella Colon Lactobacillus Methanobrevibacter (Archaea) Peptococcus Peptostreptococcus Proteus Ruminococcus Anus Staphylococcus Streptococcus © 2012 Pearson Education, Inc.

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 © 2012 Pearson Education, Inc.

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 © 2012 Pearson Education, Inc.

Upper respiratory tract Figure 27.11 Sinuses Nasopharynx Upper respiratory tract Pharynx Oral cavity Larynx Trachea Lower respiratory tract Figure 27.11 The respiratory tract. Bronchi Lungs © 2012 Pearson Education, Inc.

27.5 Normal Microflora of Other Body Regions 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 © 2012 Pearson Education, Inc.

27.5 Normal Microflora of Other Body Regions 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 © 2012 Pearson Education, Inc.

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 © 2012 Pearson Education, Inc.

27.6 Measuring 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 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 © 2012 Pearson Education, Inc.

Highly virulent organism (Streptococcus pneumoniae) Figure 27.14 Highly virulent organism (Streptococcus pneumoniae) Moderately virulent organism (Salmonella enterica serovar Typhimurium) 100 80 Percentage of mice killed 60 40 Figure 27.14 Microbial virulence. 20 101 102 103 104 105 106 107 Number of cells injected per mouse © 2012 Pearson Education, Inc.

27.6 Measuring Virulence Attenuation Toxicity 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 © 2012 Pearson Education, Inc.

Figure 27.13 TOXICITY: toxin effects are local or systemic Further exposure at local sites TOXICITY: toxin effects are local or systemic COLONIZATION and GROWTH Production of virulence factors TISSUE DAMAGE, DISEASE EXPOSURE to pathogens ADHERENCE to skin or mucosa INVASION through epithelium INVASIVENESS: further growth at original and distant sites Further exposure Figure 27.13 Microorganisms and mechanisms of pathogenesis. © 2012 Pearson Education, Inc.

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) © 2012 Pearson Education, Inc.

Figure 27.15 Figure 27.15 Adherence of pathogens to animal tissues. © 2012 Pearson Education, Inc.

27.7 Entry of the Pathogen into the Host – Adherence 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 © 2012 Pearson Education, Inc.

Figure 27.16 Figure 27.16 Bacillus anthracis capsules. © 2012 Pearson Education, Inc.

Figure 27.18 Figure 27.18 Fimbriae. © 2012 Pearson Education, Inc.

27.6 Measuring 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 © 2012 Pearson Education, Inc.

27.7 Entry of the Pathogen into the Host – Adherence Pathogen Invasion Starts at the site of adherence May spread throughout the host via the circulatory or lymphatic systems © 2012 Pearson Education, Inc.

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 © 2012 Pearson Education, Inc.

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 © 2012 Pearson Education, Inc.

27.10 Exotoxins Exotoxins Proteins released from the pathogen cell as it grows Three categories: Cytolytic toxins AB toxins Superantigen toxins © 2012 Pearson Education, Inc.

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 a-toxin kills nucleated cells and lyses erythrocytes (Figure 27.20) © 2012 Pearson Education, Inc.

Figure 27.19 Figure 27.19 Hemolysis. © 2012 Pearson Education, Inc.

Out In Efflux of cytoplasmic components Cytoplasmic membrane Figure 27.20 Efflux of cytoplasmic components Cytoplasmic membrane Out In -Toxin pore Influx of extracellular components Figure 27.20 Staphylococcal -toxin. © 2012 Pearson Education, Inc.

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 Toxins © 2012 Pearson Education, Inc.

Normal protein synthesis Protein synthesis stops Figure 27.21 Diphtheria toxin Cytoplasmic membrane Out In Receptor protein Diphtheria toxin Amino acid Figure 27.21 The action of diphtheria toxin from Corynebacterium diphtheriae. Ribosome Normal protein synthesis Protein synthesis stops © 2012 Pearson Education, Inc.

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) © 2012 Pearson Education, Inc.

Normal Acetylcholine (A) induces contraction of muscle fibers Figure 27.22 Excitation signals from the central nervous system Muscle Figure 27.22 The action of botulinum toxin from Clostridium botulinum. Normal Acetylcholine (A) induces contraction of muscle fibers Botulism Botulinum toxin, , blocks release of A, inhibiting contraction © 2012 Pearson Education, Inc.

Figure 27.23 Inhibitory interneuron Inhibition Tetanus toxin Excitation signals from the central nervous system Muscle Normal Glycine (G) release from inhibitory interneurons stops acetylcholine (A) release and allows relaxation of muscle Figure 27.23 The action of tetanus toxin from Clostridium tetani. Tetanus Tetanus toxin binds to inhibitory interneurons, preventing release of glycine (G) and relaxation of muscle © 2012 Pearson Education, Inc.

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) © 2012 Pearson Education, Inc.

Figure 27.24 Figure 27.24 The action of cholera enterotoxin. Normal ion movement, Na from lumen to blood, no net Cl movement Blood Intestinal epithelial cells Lumen of small intestine GM1 Colonization and toxin production by V. cholerae Cholera toxin AB form GM1 Vibrio cholerae cell Activation of epithelial adenylate cyclase by cholera toxin A subunits Cholera toxin B subunit Adenylate cyclase ATP Cyclic AMP Na movement blocked, net Cl movement to lumen Figure 27.24 The action of cholera enterotoxin. Massive water movement to the lumen; cholera symptoms © 2012 Pearson Education, Inc.

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) © 2012 Pearson Education, Inc.

Figure 27.25 Figure 27.25 Limulus amoebocytes. © 2012 Pearson Education, Inc.