Afghanistan (1977) Bahmian Buddha before its destruction.

Father of Oral Biology - Dutch glassmaker Antony van Leeuwenhoek discovered the first microbes in the mouth and recorded the diversity of these organisms.

Mixed communities. The mouth contains a vast number of microbial inhabitants of all different shapes and sizes.

BACTERIAL PATHOGENESIS 1. General aspects of infection 2. Transmission 3. Attachment to host surfaces 4. Invasion and inflammation 5. Toxin production 6. Mechanism for escaping host defenses

BACTERIAL PATHOGENESIS 1. An endemic infection is constantly present at a low level in a specific population (e.g. endemic malaria in some African countries). 2. An infection is an epidemic if it occurs much more frequently then usual (e.g. an epidemic of influenza in Winter). 3. An infection is a pandemic if it has a worldwide distribution (e.g. HIV infection).

BACTERIAL PATHOGENESIS Infection may imply: 1. Colonization 2. Multiplication 3. Invasion 4. Persistence of a pathogen on or within a host Infection disease - an infection that causes significant damage to the host The major mechanisms by which pathogenic bacteria cause disease : Invasiveness - the ability to invade tissues Toxigenesis - the ability to produce toxins

Symptomatic - producing symptoms. Unapparent or subclinical - a rise in antibody titer (hepatitis B and C) or isolating the organism. Latent state (e.g. recurrent herpes after primary HSV infection). Chronic carrier - the organisms continue to grow, with or without symptoms (e.g. Salmonella typhi (typhoid) can survive and multiply in the gall bladder; HBV and HCV can survive in hepatocytes after the acute phase). Chronic carriers are an important source of infection. BACTERIAL PATHOGENESIS

Virulence factors To cause a disease microbial pathogens must: 1. Enter a host - invade 2. Find a unique niche and adhere or colonize 3. Avoid or subvert the host's normal defenses 4. Multiply in that setting BACTERIAL PATHOGENESIS

BACTERIAL STRUCTURE

TRANSMISSION 1.Most infections are exogenous in origin - transmission from external sources. 2.Others are endogenous in origin caused by members of the normal flora, (e.g. uropathogenic Escherichia coli). 3. Opportunistic infections. Bacteria or fungi cause disease only in immunocompromised individuals (HIV infection, malignancies, immunosuppressive therapy).

TRANSMISSION Respiratory tract - inhalation - the airborne route. Gastrointestinal tract - ingestion - fecal contamination of food and water. Skin and genital tract - inoculation - by sexual contact, contaminated needles, skin contact, blood transfusions or biting insects. Congenital infections (transplacental) (mother-to-child) Zoonoses - animals are reservoirs of bacteria.

BACTERIAL PATHOGENESIS 1. General aspects of infection 2. Transmission 3. Attachment to host surfaces 4. Invasion and inflammation 5. Toxin production 6. Mechanism for escaping host defenses

The first step in the infective process. Bacteria and fungi have specialized structures or produce substances that facilitate their attachment to the surface of cells or prostheses (e.g. dentures, artificial heart valves). Mutants that lack these mechanisms are often non-pathogenic. Pili (fimbriae) of Neisseria gonorrhoeae and E. coli mediate their attachment to the urinary tract epithelium; Glycocalyx - extracellular polysaccharide of Streptococcus mutans - attachment to enamel surfaces. Teichoic acids - the outer layer of the Gram-positive cell wall in Staphylococci - attachment to mucosal cells. Attachment (adherence) to host surfaces

EXTERNAL STRUCTURES Pili (fimbriae) Filamentous proteins (hair-like structures) on the surface of bacterial cells, composed of protein called pilin. Mediate attachment to receptors on human cells e.g. Neisseria gonorrhoeae. Type 1 fimbriae in Enterobacteria (E.coli) which binds specifically to mannose terminated glycoproteins on eukaryotic cell surfaces.

EXTERNAL STRUCTURES Pili (fimbriae) Oral Streptococci

EXTERNAL STRUCTURES FLAGELLA Composed of helically coiled protein subunits called flagellin. MOTILITY for bacteria and CHEMOTAXIS toward nutrients. Pathogenesis of urinary tract infections by uropathogenic E. coli. Identification of Salmonella species.

(a shadow-cast electron micrograph) FLAGELLA E. coli

BACTERIAL BIOFILM A complex structured community of microbial cells that is irreversibly attached to a surface and enclosed in a self-produced, primarily polysaccharide matrix. Biofilm-associated organisms differ from planktonic (freely suspended) organisms with respect to the genes that are transcribed. Biofilms may form on a wide variety of surfaces: living tissues, indwelling medical devices, water lines, etc. Dental plaque is an example of a biofilm. The extracellular polymeric matrix protects the biofilm-associated bacteria from host defenses and antibiotics.

Staphyloccocal biofilm on the surface of medical device

BACTERIAL PATHOGENESIS 1. General aspects of infection 2. Transmission 3. Attachment to host surfaces 4. Invasion and inflammation 5. Toxin production 6. Mechanism for escaping host defenses

INVASION and INFLAMMATION 1. Collagenase and hyaluronidase Degradation of collagen and hyaluronic acid, spread of bacteria through connective tissue (Streptococcus pyogenes). 2. Coagulase - Staphylococcus aureus, the formation of a fibrin clot from fibrinogen. 3. Immunoglobulin A (IgA) protease degrades IgA on mucosal surfaces, attachment of N. gonorrhoeae, Haemophilus influenzae and Strep. pneumoniae to mucous membranes. 4. Leucocidins, destroy neutrophiles and macrophages; the periodontopathic organism Actinobacillus actinomycetemcomitans possesses this enzyme.

BACTERIAL PATHOGENESIS Virulence factors that limit the ability of the host defense mechanisms, especially phagocytosis: 1.The polysaccharide capsule (Strep. pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Klebsiella pneumoniae, Salmonella typhi) 2.The cell wall proteins of the Gram-positive cocci: M protein of Strep. pneumoniae protein A of Staph. aureus.

BACTERIAL STRUCTURE Motility Attachment Anti - phagocytic Attachment

BACTERIAL PATHOGENESIS Two types of inflammation: pyogenic and granulomatous In pyogenic (pus-producing) inflammation, neutrophiles predominate. The common pyogenic bacteria: Staph. aureus, Strep. pyogenes and Strep. pneumoniae. In granulomatous (granuloma forming) inflammation, macrophages and T cells predominate. The most important organism - Mycobacterium tuberculosis (cell-mediated immune responses).

Pustular impetigo Pyogenic (pus-producing) inflammation - S. aures

BACTERIAL PATHOGENESIS 1. General aspects of infection 2. Transmission 3. Attachment to host surfaces 4. Invasion and inflammation 5. Toxin production 6. Mechanism for escaping host defenses

ENDOTOXINS - the cell wall lipopolysaccharide (LPS) of Gram-negative bacteria (both cocci and bacilli), released when bacterial cell dies. The lipid A portion of LPS is responsible for endotoxin activity. Compare to exotoxins, the toxicity of endotoxin is LOW! Endotoxins cause fever, shock and other generalized symptoms. Toxin production

Exotoxins - Gram-positive and Gram-negative bacteria. Polypeptides (proteins) - genes are located on plasmids or lysogenic bacterial viruses. Two subunits (domains): A subunit ("active" - has inhibitory activity) B subunit (binds to a specific cell surface receptor) Exotoxins are among the most toxic substances known. Exotoxins are good antigens and induce the synthesis of protective antibodies (antitoxins). The toxicity of exotoxin can be neutralized (formaldehyde, acid or heat), and these TOXOIDS are used in vaccines because they retain their antigenicity. Toxin production

Neurotoxins (Tetanus toxin, Diphteria toxin, Botulinum toxin) Enterotoxins - enteric syndromes (diarrhea and/or vomiting) E. coli, Vibrio cholerae, verotoxin (E. coli with the O157:H7 serotype - undercooked hamburgers in fast-food restaurants). Pertussis toxin (Bordetella pertussis) - the whooping cough. Superantigens The toxic shock syndrome toxin (TSST) of Staph. aureus, Staphylococcal food poisoning Streptococcal pyrogenic exotoxins [SPEs] Toxin production

Toxin can be completely responsible for the characteristic symptoms of the disease. EXAMPLES: The food poisoning caused by Staph. aureus or Bacillus cereus. The botulism caused by Clostridium botulinum. The food poisoning caused by toxin occurs much sooner than other forms of gastroenteritis! Bacteria do not need to grow for the symptoms to occur! Toxin production