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
(No Transcript)
21
(No Transcript)
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