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Obligate intracellular bacteria - Coggle Diagram
Obligate intracellular bacteria
Introduction
Common features
depend strictly on the host cell for replication and survival
mostly small reduced genomes
pass a developmental cycle
different forms (infectious- non-replicating; non-infectious-replicating)
Infection cycle
adherence
invasion + inclusion
differentiation
replication or persistance
re-differentation
lysis
adherence
Chlamydia trachomatis
-> Trachona, conjunctivitis, urogental infection
Chlamydia pneumoniae
-> Respiratory tract infection
Chlamydia psittaci
-> "Psittacosis/Ornitosis": atypical pneumonia
Richettsia prowazekii
-> Typhus fever
Anaplasma phagocytophilum
-> Human granulocytic anaplasmosis and tick-borne fever
Ehrlichia chaffeensis
-> Human monocytic ehrlichiosis
Coxiella burnetii
-> Acute Q-fever (pneumonia), chronic Q-fever (endocarditis)
Mycobacterium leprae
-> Leprosy
Chlamydiales
Intracellular niche
for development of elementary bodies and reticulate bodies + generation of progeny
tasks: 1) preventing the maturation and fusion with lysosome 2) facilitaing the acquisition of nutrients 3) protecting the bacteria from intracellular immune surveillance auch as autophagy
inclusion modified by inclusion membrane proteins (Incs): class of proteins secreted by the T3SS
C. trachomatis
Metabolic adaptation
import amino acids from the host cell for protein biosynthesis
import host cell-provided glucose 6-phosphate for cell wall biosynthesis
Ala, Asp & Glu made
de novo
probably using dicarboxylates from citrate cycle of host cell
central carbon metabolism
Glu-6-P/Glycogen -> ATP
Glu-6-P -> cell wall
ATP -> Membran potential
AS -> Protein cell wall
Lipid -> Membrane
selectively take up glutamine
Cell division in
Chlamydia
no FtsZ required for binary fission most bacteria use for cell division
division by a polarized cell division process similar to budding process
transient PG ring following constriction at the septum
take up glutamine for PG biosynthesis in axenic culture
transform to reticulate bodies in axenic culture if glutamine is present
Serotype A-C: Trachoma, 140 million people affected, 2.5 million blind people, endemic in Africa, Asia, and SouthAmerica
Serotype D-K: Sexual transmitted disease (cervicitis, urethritis, PID), 131 million new patients per year, Reactive Arthritis (Reiter Syndrom), Conjunctivitis (“Swimming-pool“ and new-borns), Atypical pneumonia in newborns
Serotypes L1-L3: Lymphogranuloma venerum
Increased risk of co-infection with HIV and/or Neisseria
Association to cervix and ovarian cancer
Diseases associated with A-C
Trachoma: severe kerato conjunctivitis
5-7 days post infection severe conjunctivitis
Formation of typical follicles at inner side of the upper eye lid
Trichiasis – damage of the cornea and blindness
Risk factor for cervix and ovarian cancer?
Epidemiological evidence
Persist for long times without causing symptoms
Induce DNA damage
Manipulate oncogenic signaling
Desconstruction of cell wall
free-living bacteria such as
E.coli
are wrapped by a shape determining PG(peptidoglycan) sacculus for osmotic stabilization and synthesis of septal PG protects dividing cells against lysis
minimal PG strucutre only needed at certain times and location to facilitate cell division and control immune modulation
Protochlamydia
: structure of septal PG unknown
Waddlia
: circular structure of PG
Chlamydia
: narrow PG ring transiently formed during cell division
Host pathogen interactions
downregulation of major tumor supressor p53 induced by
Chlamydia
infection
stabilization of p53 severely impairs chlamydial development
degradation of p53 unleashes the pentose phosphate pathway for metabolic support
G6PD expression overcomes the DNA damage response and rescues chlamydial growth
Subversion of cell autonomous defense
Chlamydia secrete the deubiquitinase Cdu1 into the inclusion membrane
Cdu1 deubiquitinates the inclusion membrane during infection
Cdu1 protects against cell-autonomous host defense
Subversion of cellular innate immune defence: neutrophils
CPAF
: chlamydial protease-like activity factor -> serine protease, conserved within Chlamydiales
secreted 24h(?) post infection
Neutrophils the first line of immune defence
FPR2 present on the surface of neutrophils is targeted by CPAF
dampens G-protein-coupled receptor signalling -> preventing downstream activation of neutrophils + enabling pathogen survival
C. pneumoniae
High prevalence (Age 20: 60 %; age 60: >90% seropositiv)
Atypical pneumonia
Arteriosclerosis
Juvenile asthma
Associated with atherosclerosis?
C. pneumoniae replicate in epithelial cells (a) and persist in monocytes and macrophages (b)
C. psittaci
Cause of psittacosis: Life threatening pneumonia
Transmitted by contact with birds (feces or secretions)
Bacteria can survive outside the cells for several weeks
Biosafety L3 organism
Rickettsia
The pathogen
Gram-negative, obligate intracellular, pleomorphic rods
Arthropod (tick, flea, louse) and vertebrate host
•
Rickettsia rickettsii
(Rocky Mountain spotted fever (RMSF)
•
Rickettsia conorii
(Mediterranean spotted fever)
•
Rickettsia prowazekii
(epidemic typhus)
•
Rickettsia typhi
(murine typhus)
•
Orientia tsutsugamushi
(scrub typhus)
Disease
Rickettsia rickettsii
Rocky Mountains spotted fever:
Highly lethal; headache, fever, myalgia, nausea and vomiting early in the illness; if untreated, systemic infection, multiorgan failure, encephalitis, interstitial pneumonia, non-cardiogenic pulmonary oedema and adult respiratory distress syndrome. In severe cases, hypovolaemia and hypotensive shock result in acute renal failure
R. prowazekii
Epidemic typhus:
Fever, headache, mental confusion and rash;
Can cause latent infection: Brill-Zinsser disease – mild form of typhus
Life cycle of tick.borne Rickettsiae
Uninfected tick feed on infected rodents -> infected larval tick or infected nymphal tick
infected larval tick feed on uninfected rodents
infected nymphal tick -> tick moults, trans-stadial maintenance -> infected female adult tick
infected female adult tick infects human or -> transovarial transmission to infected eggs becoming infected larval tick
Host cell interactions
Rickettsiae enter host via skin or mucosa
Invade endothelial cells
Escape phagosome with the help of hemolysin and phospholipase
Spread from cell to cell or by rupture of the cell
Cells damage causes disruption of tight junctions vascular permeability
Anaplasma/Erlichia
Gram-negative obligate intracellular bacteria
Order Rickettsiales
Transmitted between mammals by blood-sucking ticks
Replicate inside mammalian white blood cells and tick salivary-gland and midgut cells
Diseases
Anaplasma phagocytophilum
: Human granulocytic anaplasmosis (HGA)
Ehrlichia chaffeensis
: Human monocytic ehrlichiosis (HMA)
Symptoms: Fever, headache, myalgia, anorexia, chills, leukopenia
Strongly increasing incidence in USA
Infection cycle
• Wild animals are primary reservoirs
• Domestic animals occasionally serve as secondary reservoirs
• Humans are infected by the bite of infected ticks
Subversion of the host
• No own synthesis of LPS and peptidoglycan: Employ host cholesterol to stabilize membrane
• Anaplasma uses the autophagic pathway to generate niche for replication in Granulocytes
• Anaplasma interferes with apoptosis signaling
Coxiella
Cause of Q-fever
Organism isolated from patients (Burnet and Freeman) also found in ticks (Davis and Cox)
Large and diverse zoonotic reservoir: arthropods, birds, fish, variety of wild and domestic mammals; most frequent in sheep, cattle and goats
Infection by contact with infected animals or directly by inhalation of pathogen
-containing dust or tick feces - Worldwide occurrence
Disease
Cause of Q-fever: an acute flu-like illness, prolonged high fever, headache, and malaise
About 50% of infections without clinical signs/symptoms of disease.
Atypical pneumonia, severe headache, hepatitis
Rare: chronic disease (endocarditis)
Bioweapon category B select agent because: aerosol transmission, a low infectious does, and the debilitating nature of acute Q fever
C. burnetti
The pathogen
Polymorphic, small (0.3-0.7 µM) gramnegative bacterium
Very large genome of ~2 Mb
Biphasic developmental cycle:
-Nonreplicative small cell variants (SCV)
-Metabolically active, replicative large cell variants (LCV)
May form spores
Placenta usually heavily infected
Replicate in macrophages, free-living amoebae and in gut epithelium of ticks
Mycobacterium leprae
Leprosy is known since ancient times (Egypt, India, East-Asia)
Today: main regions India, Indonesia, Burma, also Brazil, Nepal, Mozambique
About 220.000 leprosy patients worldwide
Close contact with infected person (only other reservoir Armadillo); highly enriched in mother’s milk
Can be grown in the footpad of mice
Disease
Massive damage of nerves
Lepromatous form
:
most severe form
missing cellular immune reaction
full replication of pathogen in macrophages
systemic spread and severe skin lesions
Tuberculoid form
:
less severe without systemic spread
immune reaction and control of bacterial replication
Sometimes severe nerve damage
Tropism to nerve cells with Schwann's sheath leads to loss of neurons
Pain and heat insensitivity
Severe injury, but no pain
Secondary infections lead to necrosis and loss of infected tissue
The pathogen
Acid resistant rod, 1-5 µm
Typical mycobacterial cell wall (waxes, mycolic acids)
Replicate in macrophages and in Schwann cells