BMS2052 Lecture Notes - Lecture 4: Myositis, Siderophore, Apoptosis
30 May 2018
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Week 2. Mechanisms of Bacterial Pathogenesis
MECHANISMS OF BACTERIAL PATHOGENESIS I
• Lower respiratory tract infections are the 3rd leading cause of death worldwide
• Some bacteria are exclusively pathogenic (virulent/aggressive) and are found only associated
with disease eg. M. tuberculosis
• Some have pathogenic and non-pathogenic strains eg. E.coli or Shigella
• Microbes can colonise all exposed human/animal surfaces
Normal body sites:
o Eye
o Outer ear
o Skin
o URT/nasopharynx
o GIT
o Genital tract (females – vaginal)
o Urogenital tract (males – distal urethra)
Presence of microbes outside these niches indicates an infection
• Normal flora:
o Acquired shortly after birth
o Changes continuously through life
o Helps protect us from disease by:
Competing with invaders for space and nutrients – including pathogens and
other normal flora
Producing compounds that kill or inhibit other bacteria – i.e. lowering pH so that
othe ateia at go
Keeping each other in check eg. Lactobacillus in healthy vagina keeps it acidic
and keeps other bacteria at bay
o Aids digestion
o Produces vitamins (B12 and K)
o Maintain acidic vagina
o Boost immunity (antigenic stimulation)
o Regulate body weight – by how you metabolise fats and glucose
find more resources at oneclass.com
find more resources at oneclass.com
o Opportunistic infections can occur when there is a breakdown of normal microbiota (eg.
antibiotic use of reduced immunity)
o HAI (hospital acquired infections) occur when normal microbiota is transferred to or
between healthy compromised individuals (especially patients)
• Pathogen: organism able to cause disease
• Pathogenicity: measure of the ability of an organism to cause disease (virulence)
-how much of it do you need to be affected
• Virulence factor: factors required by the microorganism that enable it to cause disease
• Bacteria/microbes exist along a continuum from commensal to pathogen
• Pathogenesis is determined by the interaction of the pathogen with the host and vary depending
on:
o Particular pathogen i.e. vibrio cholera only infects humans
o Particular host i.e. salmonella enterica causes severe typhoid fever in humans but not
mice
o Host microbiota i.e. C.difficile doest oall ause ha util i the pesee of
antibiotics
• The oe health oept eogises that the health of humans is connected to the health of
animals and the environment
-6 out of every 10 infectious diseases in humans are spread from animals
• Why do pathogens cause disease?
o Pathogens express virulence determinants (factors) not expressed by commensal
organisms
o Virulence factors mediate:
Colonisation
Adhesion
Anti-phagocytic action/immune evasion mechanisms
Tissue damage
find more resources at oneclass.com
find more resources at oneclass.com
• Kohs postulates: 4 iteia desig to estalish ausatie elatioship etee a ioogais
and a disease
Postulate 1
o Microbe must be present in every case of the disease
o Limitation: no host factors are taken into account i.e. carrier states or
oppotuisti ifetios if it at oeoe host the it at ause
infection)
o Virulence gene is always found in strains with a particular virulence
phenotype
Postulate 2
o Microbe must be isolated from the diseased host and grown in pure culture
o Liitatio: ephasis o ailit to ultue the ogais ut a at e
cultured eg. chlamydia is hard to isolate
o Gene should be expressed in the host
Postulate 3
o Disease must (should) be reproduced when a pure culture is introduced
onto a healthy (susceptible) host
o Limitation: organisms can lose virulence/pathogenicity during laboratory
culture
o Mutation/inactivation of that particular gene abolishes/reduces the
virulence phenotype
Postulate 4
o Microbe must be recoverable from an experimentally-infected host
o Limitation: disease may not require the organism to infect the host eg.
toxins although this is rare
o Reintroduction of the gene reconstitutes the virulence phenotype
Postulate 5
(new)
o Effective therapeutic or preventative measures should eliminate disease
o Limitation: requires a stable/susceptible animal model
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Normal body sites: eye, outer ear, skin, urt/nasopharynx, git, genital tract (females vaginal, urogenital tract (males distal urethra) Presence of microbes outside these niches indicates an infection: normal flora, acquired shortly after birth, changes continuously through life, helps protect us from disease by: Competing with invaders for space and nutrients including pathogens and other normal flora. Producing compounds that kill or inhibit other bacteria i. e. lowering ph so that othe(cid:396) (cid:271)a(cid:272)te(cid:396)ia (cid:272)a(cid:374)(cid:859)t g(cid:396)o(cid:449) 6 out of every 10 infectious diseases in humans are spread from animals: why do pathogens cause disease, pathogens express virulence determinants (factors) not expressed by commensal organisms, virulence factors mediate: Tissue damage: ko(cid:272)h(cid:859)s postulates: 4 (cid:272)(cid:396)ite(cid:396)ia desig(cid:374) to esta(cid:271)lish (cid:272)ausati(cid:448)e (cid:396)elatio(cid:374)ship (cid:271)et(cid:449)ee(cid:374) a (cid:373)i(cid:272)(cid:396)oo(cid:396)ga(cid:374)is(cid:373) and a disease. Postulate 2: microbe must be isolated from the diseased host and grown in pure culture, li(cid:373)itatio(cid:374): e(cid:373)phasis o(cid:374) a(cid:271)ilit(cid:455) to (cid:272)ultu(cid:396)e the o(cid:396)ga(cid:374)is(cid:373) (cid:271)ut (cid:373)a(cid:374) (cid:272)a(cid:374)(cid:859)t (cid:271)e cultured eg. chlamydia is hard to isolate.
