Medical Bacteriology Flashcards
Types of pathogens?
- opportunistic
- primary pathogen
define Opportunistic
normally non-pathogenic but can cause disease when opportunity arises
define Primary pathogen
can cause disease in a host regardless of host immune or the resident microbiota
To be a successful pathogen, you must…
Gain entry to the host
Access nutrients from the host to multiply
Evade host defences
Escape and colonise new host environments
define virulence
the ability to cause disease.
what is an example of high virulence?
Highly virulent: Streptococcus pneumoniae
- Just a few cells can establish an infection
what is an example of low virulence?
Lower virulence: Salmonella typhimurium
- 1000+ cells must be ingested to establish infection
- Infection results in a self-limiting gastroenteritis in humans.
define virulence factor
any aspect of a pathogenic microorganism that enables it to give rise to disease.
define virulence gene
gene in a pathogenic microorganism which is responsible for its ability to cause disease.
define virulence plasmid
bacterial plasmid that carries genes, e.g. toxin genes, that render its bacterial host pathogenic
Some bacterial pathogens are successful due to
secretion of toxins
Some bacterial pathogens are successful due to secretion of toxins – these include
Clostridium tetani which infects wounds from soil – it is slow growing but is virulent because of the release of a toxin.
Some pathogens succeed by dividing and
overwhelming the host by their invasiveness (e.g. S. pneumoniae which evades host defences by means of encapsulating its cell with a polysaccharide capsule).
Virulence factors can include
molecules that allow bacteria to avoid detection or factors that have an effect on the host allowing easier growth or access to nutrients
Streptococcus pyogenes produces
streptokinase
Streptococcus pyogenes produces streptokinase which dissolves
blood clots
Streptococcus pyogenes produces streptokinase which dissolves blood clots – enabling the bacteria to
bypass the clotting system which normally limits infection
Hyaluronidases that break down the extracellular matrix allowing
greater access to nutritents.
Some of the best characterised virulence factors are
toxins that act upon cells (e.g. Murine toxin in plague).
two kinds of immunity in your body:
innate
adaptive
what does innate immunity provide protection against?
Protection against infection by fixed, relatively non-specific defence mechanisms
innaate immunity is
non specific
innate immunity examples
- Anatomical barriers (e.g. epithelium, mucus, tears, lysozyme)
- Inflammatory response
- Complement (works with adaptive immune response)
- Leukocytes: white blood cells
the inflammatory response recruits
defence cells to the area
whats complement?
Cascade of proteins which destroy targeted cells
examples of leukocytes (white blood cells)?
- natural killer cells, mast cells, eosinophils, basophils
- macrophages, neutrophils, dendritic cells, T helper cells
what is the adaptive immune response?
Selective response mounted by immune system in which specific antibodies/cytotoxic cells are produced against an antigen recognised as foreign to the body.
adaptive immune response results in
long-lived and specific immunity against the pathogen.
vaccinrd exploit
the adaptive immune response.
After phagocytosis defence cells present antigens from the pathogenic bacteria at
the cell surface in association with major histocompatibility complex proteins (MHC) class II
After phagocytosis defence cells present antigens from the pathogenic bacteria at the cell surface in association with major histocompatibility complex proteins (MHC) class II and migrate to
the lymph node where it will interact with cells directing the adaptive immune response.
Complement aids in
the removal of bacteria
Complement aids in the removal of bacteria. One pathway is
to form of membrane attack complexes in bacterial membranes, punching them open.
Complement aids in the removal of bacteria. One pathway is to form of membrane attack complexes in bacterial membranes, punching them open.
Additionally fragments …
… signal to immune cells and act as signals to macrophages to phagocytose bacteria
The complement system can be activated by either
the adaptive immune response (by associating with antibody/antigen complexes on the surface of bacteria or by the recognition of bacterial wall components.
Invasive pathogens are generally
encapsuklated
Bacteria with capsules are more likely to
evade detection because their PAMPs are hidden (cloaked).
Host macrophages recognise
PAMPS
what are pamps
pathogen associated molecular patterns
exampels of pamps
lipopolysaccharide and flagellin
Bacteria evade detection by:
1) Invisibility
2) Provide a moving target
3) Mimicry
whats invisibility of bacteria?
Mask potential PAMPs under a capsule.
describe the moving targets of bacteria?
have variable external components which change regularly. Many capsule components are unique to particular strains and consist of a multiplicity of different repeating sugar moieties
what is mimicry?
some bacteria (eg Group A Streptococcus) express glycoproteins that are identical to human cell glycoproteins (e.g. hyaluronan)
To invade or attack host cells, bacteria need to
attach to them.
Adhesion works via
recognition between proteins either at the tips of pili or within the cell wall and glycoproteins or glycans on the host cell surface
define endotoxins
integral components of bacterial cells, usually only released during damage.
Lipid A is an
endotoxin: induces host fever and other responses.
a high dose of endotoxin initiates
septic shock
Endotoxins: integral components of bacterial cells, usually only released during damage.
Remember lipopolysaccharide?
Lipid A is an endotoxin: induces host fever and other responses.
High dose: initiates septic shock.
Triggers…
… cascade of cytokines which damage host tissues.
exotoxin secreted by
bacteria
exotoxins may be specific or
general
Diptheria is a
toxin-mediated infectious disease. AB toxin causes inhibition of protein synthesis.
Secretion systems of various types:
-Release enzymes
-Assist host cell invasion
-Some inject components into host cells, changing their responses.
Type III secretion systems rely on …
proteins similar to those forming the base of the flagellum – proteins are secreted through the pore via a ‘needle’ into a target cell
Type IV secretion systems are derived from
pilus proteins.
cholera is tradmitted by
vibrio cholerae
how is cholera transmitted
infection is transmitted via water contaminated by a sufferer or through shellfish
cholera causes
epidemics and has been responsible for many millions of deaths
whats the mode of action of Cholera toxin? [FULL]
- The AB exotoxin binds to gut epithelial receptor (GM1)
- Subunit A is internalised by endocytosis and activates G protein.
- G protein activates adenylyl cyclase (AC). Converts ATP to cAMP (a signalling protein).
- cAMP stimulates cystic fibrosis transmembrane conductance regulator pathway which makes the cell lose Cl- ions.
- Osmotic diarrhoea.
in the cholera toxin - mode of action, what does the AB exotoxin bind to?
gut epithelial receptor (GM1)
in the cholera toxin - mode of action, subunit A is internalised by…
… endocytosis and activates G protein
G protein activates
adenylyl cyclase (AC)
G protein activates adenylyl cyclase (AC). Converts …
… ATP to cAMP (a signalling protein).
cAMP stimulates …
… cystic fibrosis transmembrane conductance regulator pathway which makes the cell lose Cl- ions.
whAT is the secretion of V. cholerae ?
harpoon-like type VI secretion System
Adjacent cells –
punctured, toxic effector proteins delivered
what are the clusters of Vibrio choleraegenomes ?
Aux clusters 1, 2, and 4
Aux clusters 1, 2, and 4 share a
canonical hcp, vgrG, tap, effector, immunity gene organization
what is Hcp ?
Hemolysin-coregulated protein hexamers
Secreted VgrG proteins interact with …
… toxic proteins (called effectors) to aid in their delivery.
what is vertical gene transfer?
from parent to offspring
goes down the generations
what is horizontal gene transfer (HGT) ?
- Acquisition of genes by one species from another species.
- Can be called “lateral gene transfer”
- Gene goes “sideways”
- Common in bacteria (rare in eukaryotes)
what are the three mechanisms of horizontal gene transfer?
- Transformation
- Conjugation
- Transduction
whats transformation ?
DNA enters bacterial cell
whats conjugation?
bacterial equivalent of sex: conjugation tube forms between two cells and genetic material is exchanged.
whats transduction ?
genets transferred by carriage as part of bacteriophage
what are Pathogenicity islands?
Many virulence genes in compact distinct genomic (islands) (10-200kbp)
how are pathogenicity islands aquired?
Acquired by HGT
pathogenicity islands have a different G+C% content than
bacterial chromosome
many pathogens have which population structure?
Many pathogens have clonal population structure
1 clone may be responsible for widespread disease
Examples of pathogenicity island contents…
Iron uptake systems
Adhesins
Pore-forming toxins
Superantigens
Secreted lipases and proteases
Proteins transported by type I, III, IV and I secretion systems
Antibiotic resistance
Escherichia coli commensal bacterium, most strains..
… harmless
what strain of e.coli is harmless?
Escherichia coli commensal bacterium
Escherichia coli commensal bacterium assists with…
… food metabolism
Some strains of Escherichia coli commensal bacterium have acquired…
… genes by horizontal gene transfer, transforming into pathogens
Five categories of diarrheagenic E. coli recognised by
serotyping
Many virulence factors are derived from
bacteriophages, plasmids or transposons.
what are transposons?
DNA sequences that possess the property of inserting themselves elsewhere on the chromosomes by a process called transposition.
where do transposition occur?
Occur in prokaryotic and eukaryotic genomes.
the simplest bacterial insertion sequences carry only
gene necessary for their own transposition.
Larger transposons carry
other genes, e.g. antibiotic resistance.
what is Yersinia pestis ?
Gram-negative, facultative aerobe. Rod shaped, encapsulated.
what family does Yersinia pestis belong to?
Family Enterobacteriaceae
Yersinia pestis causes…
… Plague/the black death
the black death killed?
Killed up to 40% of population.
when was black death?
1347-1351 in Europe.
the black death caused…
… bleeding under the skin and necrosis - hence “black death”.
the plague caused infection in 3 forms…
1) Bubonic
2) Septicemic
3) Pneumonic
bubonic plague effects?
infects lymph nodes causing them to swell into buboes. 70% mortality.
Septicemic in the
blood stream
Pneumonic: inhaled or reach lungs via
lymph or bloodstream
Pneumonic: inhaled or reach lungs via lymph or bloodstream. Few symptoms before
large amounts of bloody sputum.
pneumonic plague spreads from
person to person in the pneumonic stage
how is plague treated?
Treatable by antibiotics, e.g. streptomycin or gentamicin injection. Prompt treatment: 5% mortality.
Septicemic and pneumonic onset speed
so rapid that antibiotics are usually too late
Fleas circumvent the
skin barrier
Plasminogen activator function?
removes blood clots, allows infection to spread. Encoded on virulence plasmid.
Adhesin (YadBC) encoded on
chromosome
Type III secretion system for
Yop proteins
type III seceretion syste, inkjected into
host cells.
some Type III secretion system form…
… protein-lipoprotein complexes in cell wall to inhibit phagocytosis
Virulent strains secrete
Murine toxin
what is Murine toxin ?
a lethal respiratory inhibitor in mice, which also causes systemic shock and liver damage.
Yop proteins secreted into …
… human target cells (e.g. macrophages) disrupt normal cellular activity and result in cell death
Plague is still endemic in
some areas, especially drier regions
plague is enzootic in
rodent populations
- Intermediate host: fleas
- Some rats carry chronic infections
when was plague imported to the united states?
Imported to United states in 1900s.
If rodent population crashes in urban setting, fleas can
switch hosts and transmit to humans.
Plague control?
- Good sanitary control
- Control rodent populations in urban centres.
- Monitoring and prompt response:
- Treatment
- Quarantine of exposed individuals
Colonisations of commensal bacteria starts after
birth
Colonisations of commensal bacteria starts after birth and includes
the skin, oral cavity, upper respiratory tract and gastrointestinal tract.
what do commensal nbacteria inhabit?
Inhabit mucosal and epidermal surfaces in humans, in the normal, non disease state
Microbiome plays an important role in
defence against pathogens.
what do microbiome act on?
Act on the host’s immune system to induce protective responses that prevent colonisation and invasion by pathogens
the microbiome can directly …
… inhibit the growth of respiratory pathogens for example by producing antimicrobial products/signals and competing for nutrients and adhesion sites
Microbiome refers to the
micro-organisms in a particular habitat
how many microorganisms in the gut microbiota ?
Approximately 100 trillion micro-organisms (most of them bacteria, but also viruses, fungi, and protozoa) exist in the human gastrointestinal tract
Microbiome can influence …
… host’s fitness, phenotype, and health.
describe the Association between reduced diversity and disease.
Higher bacterial diversity = Indicator of Healthy Gut
Lower bacterial diversity = Reported in GI disease (IBD, Crohn’s)
human commensal bacteria in the mouth?
Mouth – Streptococcal spp.
human commensal bacteria in the stomach?
Gram +ve, Proteobacteria, Actinobacteria
human commensal bacteria in the small intestine
small intestine – Fusiform anaerobes
human commensal bacteria in the large intestine?
E. coli (facultative anaerobe), Clostridium, Bacteroides, Gram +ves, methanogens.
what is C. diff ?
a capsule-shaped bacterium that causes inflammation of the colon - colitis
what does c.diff produce?
produces two toxins - A and B
C. difficile that causes diseases is found…
… in the feces
spores can survive for
long periods in the environment (surfaces in a room)
spores can survive for long periods in the environment (surfaces in a room) and be spread by …
… hands that touch conatimnated surfaces
how is c. diff transmitted?
person to person fecal-orally
is c.diff gram + or - ?
gram positive
is c diff aerobic or anaerobic ?
anaerobic
c diff is a commensal flora of
human intestines (2-5%)
c diff still has
pathogenicity
c. diff is extremely
antibiotic resistant
the c. diff genome consists of..
… a circular chromosome and a circular plasmid
c. diff is [..] forming
spore forming
what does c. diff stand for?
Clostridioides difficile
c diff is a bacterium whihc causes…
… an infection of th elarge intestine (colon)
c. diff infections symptoms?
Symptoms can range from diarrhoea to life-threatening colon damage.
illness frlom c diff typically after
use of antiboitoc medications
Illness from C. difficile typically after use of antibiotic medications - which
remove the commensal bacteria which keep C. difficile in check.
C.difficile can also secrete …
…proline-based cyclic dipeptides that can inhibit gut bacteria, including commensal Clostridium species, maintaining its dominance.
who does c. diff commonly affect?
Commonly affects adults in hospital / long term care. Costly to health services.
Certain medical conditions or procedures may
make you more susceptible to a C. difficile infection
c diff sometimes cant be treated with
antibiotics
c diff sometimes cant be treated with antibiotics - cases of people with…
… recurrent / refractory disease
what is The Microbiome Treatment Centre (University of Birmingham) ?
First UK Medicines & Healthcare products Regulatory Agency licensed facility, providing FMT for clinical trials and for the treatment of patients with recurrent and refractory
Clostridium difficile infection.
