11 + 12. Emerging bacterial infections Flashcards
what is an emerging infection?
an infection that is newly appeared in a population or previously existed but rapidly increasing in incidence or geographic range
what is a re-emerging infection?
infections that existed in the past but are now rapidly increasing in incidence or geographical or human host range
what are some misconceptions about infectious diseases?
that the period where they would be interesting or a problem is over and they are not worth research
what are some things that decrease the incidence of infectious diseases?
better housing
safer food and water
improved healthcare and immunisations
improved hygiene
better education
why are disease death rates slowly increasing again?
HIV and other diseases
what increases the incidence of emerging infectious diseases?
society getting older
more leisure time and travel
changes in technology
industrial food production
International travel
Complacency in public health and lack of funding
pathogens changing and adapting
what is tularaemia?
a bacteria disease classically associated with contact with infected animals or arthropod vectors
what are the different manifestations of tularaemia?
skin - lesions and flu like symptoms
ingestion - contaminated meat
inhalation - aerosol, 30% fatal
where is tularaemia normally found?
sub arctic northern hemisphere in remote areas
what type of infection is tularaemia?
zoonotic
where is tularaemia found that it was not previously thought?
in the southern hemisphere where it as differentiated into a number of branches
what bacteria causes tularaemia?
Francisella Tularensis
what is Francisella tularensis?
small
gram-negative
coccobacillus
intracellular pathogen
why is Francisella tularensis hard to culture?
normally intracellular so needs lots of supplements to be cultured
what is the natural reservoir of Francisella tularensis?
thought to rodents but they suffer so cannot be a reservoir
thought to be a protozoa amoeba
why does Francisella tularensis have a degraded genome?
intracellular so relies on host cells for most functions
why is the Francisella tularensis genome degraded?
10% of coding genes are non functional
insertion sequences
deletions
frameshifts
what functions can Francisella tularensis not do?
cannot Assimilate sulphur so cannot make cysteine
cannot make valine, isoleucine, theanine
what is the GC content of Francisella tularensis’s genome?
low GC content
how does Francisella tularensis change macrophage uptake mechanisms?
altered uptake of bacteria using pseudopod loops
altered uptake affects the next stages of degradation
what macrophage mechanism does Francisella tularensis inhibit?
the Reactive oxygen species burst which affects enzyme activation
what is the Francisella tularensis pathogenicity island?
a part of the genome with different GC content that massively contributes to pathogenicity
each genome can contain more then 1 copy
what does the Francisella tularensis pathogenicity island encode?
20 genes that encode a type 6 secretion system
what is a type 6 secretion system ?
a delivery system that injects effector proteins into host cells to disrupt phagocytosis
what is IgIC?
part of the type 6 secretion system
what does IgIC do?
it plays a massive role in inducing apoptosis in cells
why can lactate dehydrogenase be used as a marker for apoptosis?
it is released on cell death
why does tularaemia have potential to be a biological weapon?
very very transmissible
thought to have used in Stalingrad invasion
what is bacillus anthracis?
large
gram-positive rods that associate in chains
form vegetative spores
why are vegetative spores dangerous?
allows for long periods of surivial
aerosol infection
easy to store and distribute
where is anthrax endemic?
Central Asia and USA
several African countries
associated with the soil
does anthrax have outbreaks?
natural sporadic outbreaks
what are the 3 types of anthrax infection?
Cutaneous skin infection
ingestion
Inhalation - the most serious and fatal
contact with spores and bacteria
Cutaneous anthrax
associated with lesions and oedema in infected areas
antibiotic treatment is effective if given quickly
how does anthrax infect cells?
disable innate macrophage response using lethal and edema factor
what type of toxin is lethal and edema factor?
AB toxins
7 protective antigen subunits that bind and are taken up by the macrophage
LF/EF bind to the subunits and enter the macrophage
forms a channel to excrete the toxins into the cytosol
what does edema factor do?
is an adenyl cyclase
causes water efflux and swelling (edema)
what does lethal factor do?
a Zn Metal-protease
3 domains - protective antigen binding, substrate recognition and catalytic portion
degrades Mitogen-Activated Protein (MAP) kinase kinase
what do MAP kinase kinases do?
Involved in a signalling phosphorylation cascade to induce changes in gene expression
how does lethal factor target MAP kinase kinases?
on multiple kinase kinases there is a specific sequence for the enzymes to bind to
what else does lethal factor do?
cytoskeletal rearrangements in non macrophage cells
Why should melioidosis be considered a high burden neglected tropical disease?
its burden is under-recognised and cases are under-reported due to non-specific symptoms
who are most likely to be infected with melioidosis?
Agricultural workers in SE Asia to be exposed and have repeated contact
US soldiers bought it to the west in the Vietnam war
what is the melioidosis burden?
165,000 cases a year
89,000 deaths
both are very under reported
endemic in 45 countries
high mortality ~40%
what causes melioidosis?
Saprophyte B. pseudomallei
where are most melioidosis cases reported?
Thailand so we get most data from here
why is melioidosis a problem?
not much investment compared to similar diseases like Dengue
where geographically are melioidosis cases mostly located?
large clusters in SE asia and Thailand
Northern Australia
South America
these have similar environments and soil conditions
why do we find B. pseudomallei in south america?
same strains and genomes as Africa
starting to appear after the slave trade
what is the main way melioidosis spreads through SE asia?
spreads along and around the Mekong river
why is melioidosis an emerging disease?
anthropogenic spread
Environmental dispersal
increased susceptible population
type 2 diabetes increasing
antibiotic resistance
why is increasing type 2 diabetes a problem for melioidosis?
it is a risk factor for melioidosis and massive increases the risk of death from melioidosis
when was melioidosis first discovered?
1911 in Malaysia by army doctor Whitmore
how does melioidosis manifest?
skin lesions
with abscesses on the skin, liver, lungs, spleen
how do you get infected with melioidosis?
mainly farmer worker through the skin in like cuts and scraps
why is melioidosis called the great mimicker?
it can manifest in a number of ways and causes a fever which is very common for tropical diseases
what is prognosis for lung melioidosis?
1/3 dead after a month
1/2 dead after a year
what is latent melioidosis?
Asymptomatic and latent form can go undetected for decades
the longest example is 29 years
lesions in the lungs
only positive cultures when very sick
what is Burkholderia pseudomallei?
gram-negative rods lone or in clumps
complex so several different species associated with the disease
what are Burkholderiae in general?
gram-negative, motile, aerobic, non-spore forming
plant pathogens and opportunistic human pathogen
Facultative intracellular parasite
large genomes but split into 2 chromosomes
how is B. pseudomallei active in the cytoplasm?
manipulate the actin cytoskeleton
induce fusion between infected cells and new cells
forms distinct multinucleated giant cells
why is the formation of multinucleated giant cells important for B. pseudomallei pathogenesis?
crucial for the ability to form abscesses
but different from TB as not surrounded by T cells
what is the difference between B. pseudomallei abscesses and other disease abscesses?
the abscess is caused by the pathogen not the immune system
how does B. pseudomallei subvert macrophage function?
B. pseudomallei triggers low levels of IFNb so less ROS are generated
resist degradative enzymes in the phagosome
where is B. pseudomallei taken into in non phagocytic cells?
the cytoplasm
how does B. pseudomallei escape the complement?
using a polysaccharide capsule the membrane attack complex cannot reach the binding sites or binds far away to cause damage
what are the 2 secretion systems B. pseudomallei has?
type 3 SS to escape endosome
type 6 SS for cell fusion
what are secretion systems used for?
to take material from the cytoplasm of the bacteria through the host membrane and into the host cell
how can we prove type 6 SS causes cell fusion?
use Flucytosine to block the type 6 SS and we don’t see any cell fusion or multinucleated giant cells form
how does B. pseudomallei use BimA to move around the cell?
for actin motility and remodelling of the cytoskeleton
actin is used to push the bacteria around the cell (comet tails)
this is important for multinucleated cell formation
what treatments are available for B. pseudomallei?
IV ceftazidime (b-lactam) 10-14 days
Extended treatment possible
meropenem reserve agent
oral trimethoprim or sulfamethoxazole
how are B. pseudomallei intrinsically resistant to many antibiotics?
membrane bound efflux pumps to remove antibiotics before they cause damage
modified pores in membranes to prevent antibiotic entry
B-lactamase enzymes like PenA
how can B. pseudomallei acquire resistance?
mutations and plasmids
