Reservoirs and vectors Reservoirs Animal, soil, water etc - source of infection. Vectors Arthropods, especially fleas, ticks, and mosquitoes Mechanical vectors Insects carry pathogens on feet Biological vectors Pathogen replicates in vector

Microbes: Portals of entry 1)Skin: Most microbes are not able to penetrate intact skin Some fungi infect skin 2) Mucous membranes Respiratory tract: eg. Influenza virus Gastrointerstinal tract: eg. Cholera Urogenital tract: HIV Eye (conjunctiva): eg. adenovirus

Microbes: Portals of entry 3) Parenteral (Blood-borne) route: Microbe is deposited below the skin into the tissue Eg. Blood transfusion, insect bite, tatooing (eg. HIV) 4) Vertical transmission: Transmission from mother to child (eg. HIV)

What are bacteria ?

Bacterial Structure Chromosome: DNA material of the cell Cell wall: Composed of peptidoglycan the cell wall maintains the overall shape of a bacterial cell Cell membrane: Lining the inside of the cell wall it provides a boundary for the contents of the cell and a barrier to substances entering and leaving. Cytoplasm: Describes the inside of the cell and the contents

Bacterial Shapes There are 3 different shapes of bacteria Spirals (Campylobacter) Rods (Lactobacillus) Balls or cocci (Staphylococcus) Bacteria with flagella are motile

Gram stain Diff. in cell wall 1884: Hans Christian Gram; he developed this method to better visualize bacteria All bacteria may be classified as Gram positive and Gram negative

Classification of bacteria Shape Motility Gram stain Other property (eg.aerobic /ananerobic)

Mechanisms of bacterial pathogenicity

Portals of entry Penetration or evasion of host defenses Damage to host cells Portal of exit Number of invading microbes Adherence Virulence factors Microbial mechanism of pathogenicity

(1) Adherence Adherence (attachment) is often an essential step in bacterial pathogenesis or infection, required for colonizing a new host – Adhesion - Process by which microorganisms attach themselves to cells. Requires the participation of two factors: a receptor and an ligand – Microbial adherence to a eukaryotic cell or tissue surface involves complementary chemical interactions between the host cell or tissue surface and the bacterial surface.

(1) Adherence Adhesions/ligands bind to receptors on host cells – Fimbriae/ pili Escherichia coli Neisseria gonorrhoeae – M protein Streptococcuspyogenes – Glycocalyx Streptococcus mutans

Adherence examples M protein: Group A Streptococcus Pili /fimbriae: E.Coli / N. gonorrhoeae

Why is adherence important ? Ability to colonize and cause disease Ability to adhere determines the host specificity Potential drug target

(2)Formation of bacterial biofilms Quorum sensing: ability to sense population density and alter gene expression

Examples of biofilms Dental plaques

Biofilms outside the body Biofilm mats on stagnant water Biofilm mats on rocks – Yellowstone national park

What triggers biofilm formation ? Bacterial attachment to surfaces Nutritional depletion Sub-inhibitory concentrations of antibiotics A critical population density of bacteria

How do biofilms help bacteria ? Protection from immune repsonse Protection from antibiotics Help tide over periods of low nutrition Microbial chatter (communication)

Biofilms: Why do they matter ? Key mechanism in bacterial pathogenesis Important part of food chain Major cause of corrosion of metal pipes

(3) Bacterial capsule Some bacteria have a polysaccharide layer outside the cellwall called capsule Helps in attachment Helps evade host defences  Streptococcus pneumoniae  Haemophilus influenzae  Bacillus anthracis

How does the capsule help bacteria evade host defences ? Prevent complement binding and phagocytosis Escape TLR recognitionAllows survival inside phagocytosis Capsulated bacteria

Capsule inhibits phagocytosis

Capsule allows survival inside phagocytes Capsule may help resist digestion by lysosomal emzymes

Capsules allow escape of TLR recognition (TLR) No immune response

Capsules contribute to pathogenesis

(4) Bacterial cell wall Outer layer Peptidoglycan (sugars and aminoacids) The cell wall may carry some surface proteins

Mycolic acid in cellwall helps resists lysosomal digestion Mycolic acid in the cell wall resists digestion by lysosomal enzymes Mycolic acid in the cell wall Eg. Mycobacterium tuberculosis, Mycobacterium leprae

Proteins on the cell wall help evade phagocytosis Phagocytosis Immune response X Disease X Phagocytosis X Immune response Disease

(5) Bacterial enzymes (a)Coagulase and kinase (b)Hyaluronidase and collagenase (c)IgA protease

(a) Coagulase and kinase Inhibits phagocytosis Immune response – no access Antibiotics not effective Eg. Staphylococcus aureus – skin infections Strains that do not produce coagulase are not pathogenic

(b) Hyaluronidase and collagenase Digestion of connective tissues and Invasion of tissues Hyaluronidase: is present in Staphylococcus aureus (Skin infections) and Streptococcus pyogenes (Sore throat) Collagenase: is present in Clostridium perfringens (gas gangrene)

(c) IgA protease An enzyme that can degrade IgA antibodies Eg. Haemophilus influenza – causes respiratory tract infection / meningitis Help negotiate mucosal defenses.

(6) Membrane ruffling Invasins : proteins expressed on the cell surface of various pathogens that alter actin filaments of host cell cytoskeleton, allowing microbes to enter cells.