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Bacterial Interactions with Host

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Bacterial Interactions with Host Medical Microbiology SBM 2044 When describing the interaction between host and microbes, analogies to war are common, as in ... – PowerPoint PPT presentation

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Title: Bacterial Interactions with Host


1
Bacterial Interactions with Host
  • Medical Microbiology
  • SBM 2044

2
  • When describing the interaction between host and
    microbes, analogies to war are common, as in
    references to a microbial attack or invasion
    repelled by host defense systems.
  • In reality what drives microbes is not aggression
    but survival and reproduction. To succeed, many
    microbes have evolved the ability to persist in
    the body, only incidentally causing disease

3
Pathogenesis
  • The pathogenesis of bacterial infection includes
    initiation of the infectious process and the
    mechanisms that lead to the development of signs
    and symptoms of disease.
  • Infectious process
  • Once in the body, bacteria must attach or adhere
    to host cells, usually epithelial cells
  • After establishment, the bacteria multiply and
    spread directly through tissues or via the
    lymphatic system to the bloodstream.
  • E.g. S. pneumoniae

4
Microbial survival
  • To survive, microbes must do the following
  • Avoid being washed away (colonize the surfaces of
    host cells)
  • Find a nutritionally compatible niche
  • Survive the constitutive and induced defenses
  • Transfer to a new host

5
MCQ True or False?
  • Microorganisms are the worst pathogens if they
    produce asymptomatic infection, rather than death
    of the host. (T/F ?)
  • Why?
  • False. Because pathogens that normally live in
    people enhance the possibility of transmission
    from one person to another.

6
Surface colonization
  • Once the bacteria enter the body of the host,
    they must adhere to cells or a tissue surface
  • avoid being wash away
  • compete with resident flora for adherence sites
  • Complex interactions
  • net surface charge
  • surface hydrophobicity
  • binding molecules on bacteria (ligands, adhesins)
    and host cell receptors

7
Overview of interactions with host surfaces
  • Nonspecific adhesion
  • Specific
  • adhesion
  • overall, surface interactions
  • entrapment in mucin

gt 50 nm
10 20 nm
lt 2 nm
lt 1.0 nm
Hydrophobic interactions
Specific interactions
Electrostatic repulsion
Van der Walls
Weak attractive
adhesin
receptor
Weak long-range attractive
easily disrupted
Very strong irreversible
Repulsion reduced by (a) high ionic strength (b)
small diameter
8
Nonspecific adhesion
  • Weakly adhering bacteria - easily removed by
  • physical shear forces or washing
  • May allow colonisation of surfaces not subject
    to
  • strong physical/washing forces (e.g. skin,
    vagina)
  • Not sufficient to colonise e.g. urinary tract,
    small
  • intestine, etc

9
Specific adhesion
EPEC adhering to an intestinal epithelial cells
Bordetella pertussis on to ciliated tracheal cell
10
Specific adhesion
The receptor specific molecule on host surface
The adhesin specific molecule on bacterial cell
surface
Carbohydrate part of a glycolipid or glycoprotein
Usually
A surface protein (often lectins)
Others e.g. LTA in Gram
  • Specificity analogous to enzyme-substrate
    specificity

11
Types of bacterial adhesins
  • Individual protein molecules protruding from OM
    of
  • Gram-neg. bacteria, or cell-wall of
    Gram-pos. bact.
  • protrude for distances ranging from lt 10 - 20
    nm,
  • up to ca.100nm (some Gram-pos. fibrillar
    adhesins)

Example
Streptococcus pyogenes M proteins
  • Physical reasons why locating adhesins further
    away
  • from bacterial cell-surface facilitate
    contacts with
  • receptors on mammalian cells

12
Bacterial Fimbriae
  • Specialized, multimeric, adhesive appendages
  • protruding several microns - much further
    than
  • individual surface proteins.

OM
IM
13
Fimbriae on surface of a human ETEC strain
  • Strains may express gt 1 distinct type of
    fimbriae,
  • with different receptor specificities

CS3 thin, flexible
CS1
14
Adhesin-Receptor specificity
  • First noted in late 1950s
  • A particular soluble sugar, but not others,
    inhibited
  • adhesion of E. coli to cells (rbc adhesion
    model )

Specific adhesin
Specific receptor
  • By mimicking critical part of the specific
    receptor,
  • inhibitor blocked receptor-binding site of
    adhesin
  • Type I pili First E. coli adhesin identified
  • MSHA mannose-sensitive haemagglutination

15
Other bacterial species
  • Wide variety of adhesins both fimbrial
    afimbrial (e.g. invasin that recognises
    integrins)
  • Some incorporate information on
    receptor-specificity
  • in name
  • Staphylococcus aureus Fibronectin-binding
    proteins
  • Sialoprotein-binding protein
  • Streptococcus pyogenes Fibronectin-binding
    proteins
  • Collagen-binding protein
  • Others first named for various reasons only
  • later discovered to act (also) as adhesins.
  • Streptococcus pyogenes M proteins
  • Neisseria gonorrhoeae Opa proteins

16
Consequences of adhesion
1. Organism colonizes surface e.g. normal flora
2. Pathogen colonizes surface and secretes toxins
Examples
Vibrio cholerae Enterotoxigenic E. coli (ETEC)
  • Damage due mainly to action of secreted toxins
  • Damage often localized (e.g. cholera), but if
    toxin
  • absorbed efficiently (e.g. diphtheria), may
    be
  • systemic (i.e. throughout body)

17
Consequences of adhesion
3. Colonize surface and form a biofilm
  • In contrast to localised colonies, some
    pathogens
  • can form a spreading surface layer a
    BIOFILM
  • bacteria encased in a polysaccharide slime that
    aids
  • attachment and protects bacteria.
  • Simple biofilm comprises a single species
  • Staphylococcus epidermidis
  • biofilm on a catheters

18
Complex Biofilms
  • Comprise multiple species
  • Bacterial co-aggregation
  • Some species produce polysaccharides, trapping
    others

Example Dental plaque
19
Finding a Compatible Niche
  • Nutritious plasma contains sugars, vitamins and
    minerals
  • but bacteria grow sparsely on fresh plasma in a
    test tube
  • plasma lack free iron
  • Bacteria adapt by
  • use polymeric form of iron
  • siderophores which are specific for ferric iron
  • scavenging intracellular iron i.e. haemolysing
  • Specific nutrients only in certain body tissues
  • streptococci use sucrose in the mouth

20
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21
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22
Evading the Consitutive/Induced Defenses
  • The host possess
  • First line defense
  • Second line defense
  • How do microbial agents overcome these defenses?

23
Defending against complement
  • Microbes must prevent complement activation
  • Masking surface components (i.e. LPS, teichoic
    acids) that activate alternative pathway ?
    secreting capsules to cover up
  • Incorporate sialic acid into their capsular
    polysaccharides e.g. gonococci
  • Coating with circulating IgA meningococci
  • Binding of C3b with viral envelope glycoprotein
    such as in herpes simplex virus
  • Prevent access of MAC to its target, the
    bacterial outer membrane Salmonella and E. coli
    with long O-antigen polysaccharide chain

24
Avoiding phagocytosis
  • Many bacterial pathogens are rapidly killed once
    they are ingested by polymorphs or macrophages
  • But some pathogens are able to multiply within
    host cells, by shielding with normal host
    components on their surfaces

25
Avoiding phagocytosis
  • Inhibiting phagocyte recruitment and function
  • Bordetella pertussis inhibit neutrophil motility
    and chemotaxis toxin production
  • Group A streptococci produce C5a peptidase
    inactivates the chemotactic products

26
Avoiding phagocytosis
  • Microbial killing of phagocytes
  • Leukocidins kill neutrophils and macrophages
    pseudomonads, staphylococci, group A
    streptococci, clostridia
  • shigellae kills phagocytic cells
  • Escaping ingestion
  • capsules
  • reduce opsonization e.g. staphylococci protein A
    binds to IgG by the wrong end, the Fc region

27
How microbes survive inside phagocytes?
  • Inhibition of lysosome fusion with phagosomes
  • Escapes into the cytoplasm
  • shigellae, Listeria monocytogenes and the
    rickettsiae cross the membrane of the phagocytic
    vesicle and the phagosome to enter cytoplasm,
    hence protected from lysozymes
  • L. monocytogenes secretes a pore-forming toxin,
    listeriolysin

28
How microbes survive inside phagocytes?
  • Resistance to lysosomal enzymes
  • Leishmania have resistant cell surfaces and can
    withstand acidic environment
  • Inhibition of the phagocytes oxidative pathway
  • Legionella inhibit the hexose-monophosphate shunt
    and oxygen consumption in neutrophils, thus
    reducing the free radicals respiratory burst
  • staphylococci produce catalase that breaks down
    the H2O2

29
Intracellular life
  • Obligatory for viruses, but not bacteria.
  • Advantages? Protected from antibodies, and from
    some antimicrobial drugs
  • Intracellular microorganisms must be able to
  • Penetrate
  • Survive host cell defenses
  • Transmit to other cells

30
  • Penetration
  • Easy with phagocytes
  • For non-phagocytic cells, penetration must be
    induced by microbial activities
  • bind to specific receptors and send signals
  • Surviving host cell defenses
  • Transmission to other cells
  • upon lysis of the host cells, transmission
    through blood or body fluids
  • viruses spread by cell fusing with uninfected
    adjacent cells ? formation of syncytia and
    multinucleated giant cells
  • use of host cytoskeleton to spread e.g.
    Shigella, L. monocytogenes induce polymerization
    of actin at one of their ends

31
Subverting the immune responses
  • Immunosuppression
  • infectious agents may suppress the hosts immune
    responses. HIV infects the CD4 T-helper
    lymphocytes which lead to the collapse of the
    immune system.
  • tuberculosis was more common during the measles
    outbreak
  • Diversion of lymphocyte function superantigens
  • excessive stimulation of immune cells in a
    nonproductive way e.g. toxins secreted by
    streptococci are superantigens that cause
    misdirection of the immune response

32
Subverting the immune responses
  • Masquerading by changing antigenic coats
  • Trypanosomes
  • Trypanosoma brucei cause sleeping sickness
  • covered with thick protein coat called variable
    surface glycoprotein
  • have several hundred genes that encode various
    antigens, but only ONE is expressed at a time
  • Gonococci
  • periodic changes in pilin, protein of its pili
  • Influenza viruses
  • antigenic changes emerge gradually in a
    population of viruses over an epidemic season

33
Subverting the immune responses
  • Proteolysis of antibodies
  • extracellular proteases inactivate secretory IgA
    e.g. in gonococci, meningococci and Haemophilus
    influenzae
  • staphylokinase cleaves host plasminogen into
    plasmin at the bacterial cell surface
  • Viral latency
  • Herpes infection
  • herpes virus pass from one cell to another
    through cytoplasmic bridges
  • viruses do not proliferate within cells
  • other pathogens, Helicobacter pylori which
    causes gastric ulcers and Mycobacterium
    tuberculosis also maintain chronic associations
    with the host

34
Transmission of infection
  • Infectious agents are carried into a new host
    through food, aerosols, sexual contact, wound or
    soil
  • Many microbes differentiate into a transit form,
    to survive the environment
  • Chlamydiae elementary body
  • Clinical manifestation of disease by
    microorganisms often promote transmission e.g.
  • Vibrio cholerae, E. coli and Shigella cause
    diarrhoea intestinal contents secretion
  • M. tuberculosis induce coughing dispersal via
    aerosols
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