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Transcript
Micro Chapter 27: Chlamydiae: Genital, Ocular, and Respiratory Pathogens
Chlamydia are obligate intracellular pathogens
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They need to be inside host epithelial cells because they parasitize them and need host ATP
Because of this, chlamydia can’t be growth on media or plates
Chlamydia are “considered gram-negative-like”
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They don’t stain on gram stain, but have the make up of a gram-negative bacteria
o Includes an outer membrane with LPS and a cytoplasmic membrane
o They’re susceptible to β-lactams
Chlamydia trachomatis and chlamydia pneumonia are some of the most common bacteria in the world
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Chlamydia trachomatis is the most common bacterial STI
The leading cause of bacterial blindness is chlamydia
Chlamydia causes half of cases of pelvic inflammatory disease (PID)
Chlamydia types A-K – typical chlamydia STI
Chlamydia types L – lymphogranulosum venerum
Page 294 – he said just know C. trach (don’t worry about which type is which), LGV, and pneumonia
Lymphogranulosum venerum (LGV) – causes a different kind of STI than chlamydia trachomatis
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LGV invades the lymph nodes to cause inguinal adenopathy
It’s more common in Africa, S. America, and Asia
Trachoma - eye disease caused by chlamydia trachomatis types A-C
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Most common cause of preventable blindness in the world
70-90% of adults have been, or are infected with chlamydophila pneumonia
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C. pneumonia can cause respiratory illness and asthma, and also makes the chronic
inflammation of atherosclerosis worse
Chlamydial zoonoses can happen with chlamydophila psittaci, which is spread by parrots
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Illness from chlamydophila psittaci can be called psittacosis or ornithosis
Psittacosis is most common in people in contact with birds
Human-to-human transmission is rare but possible
Chlamydia can be different enough that you can split it into 2 groups: chlamydia (C. trachomatis) and
chlamydophila (C. pneumonia and C. psittaci)
Chlamydia enter us from direct contact with mucous membranes or open skin, so by sex or direct
inoculation into the eye
Chlamydophilia are acquired by breathing them in, through respiratory droplets or aerosols
Spread and multiplication of chlamydia – pics pages 296-297
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2 forms of the chlamydia are needed for infection and disease to happen
o Elementary body – infectious extracellular form
o Reticulate body – noninfectious intracellular multiplying form
Infection happens when the elementary bodies attach to epithelial cells of the conjunctiva,
respiratory, GI, or GU tracts
Next, there’s receptor-mediated endocytosis
Once inside the cell, elementary bodies adjust the endosome membrane to prevent fusion with
lysosomes
Elementary body-containing endosomes of chlamydia trachomatis then fuse with each other to
form one colony called an inclusion
o Chlamydophila pneumonia and psittaci develop independently and form multiple
inclusions in each infected cell
Elementary bodies then convert into reticulate bodies, which start multiplying into progeny
To accommodate the increasing #’s of progeny in the inclusion, chlamydia tell their inclusion
membrane to grab vesicles in the cell carrying sphingomyelin and glycerophospholipids to and
from the golgi
o This allows expansion of the inclusion, and somewhat camoflouges the inclusion
Reticulate bodies get nutrients from the cytoplasm by extending projections from their surface
into the cytoplasm, which act as “drinking straws,” allowing chlamydia to feed from the host
cell without leaving the inclusion
o These “drinking straws” may also inject stuff into the host cytoplasm to control host
functions or defend the chlamydia from the host
Reticulate bodies are osmotically fragile, so they don’t survive outside their inclusion, and can’t
bind to epithelial cells
o So in order to spread infection, the reticulate bodies have to mature back into
elementary bodies, and then they can leave the inclusion
o The signal to cause this may be when the reticulate body detaches from the inclusion
membrane
o Outer membrane proteins get cross linked by many disulfide bonds to provide the
stability elementary bodies need to survive the extracellular environment
Once the elementary body is reformed, the inclusion can either fuse with the cell plasma
membrane to exocytose the chlamydia, or the cell can be starved enough to lead to lysis
Chlamydia trachomatis is then released at the apical cell surface of columnar epithelial cells, to
spread up the upper genital tract
o LGV is instead released at the basal domain into the submucosa, to travel to regional
lymph nodes
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Each chlamydial cycle like this takes 2-3 days
Exposure of a chlamydia-infected cell to IFN-γ causes an altered state in the reticulate body
called persistence
o IFN-γ activates an enzyme to break down chlamydia tryptophan
o Persistence shows an enlarged reticulate body that is still doing processes for
multiplication, but at a much lower rate
o Genes for turning into elementary bodies are not expressed in persistence
o Persistence can still cause a weak chronic inflammation that can still cause long term
issues
Damage from chlamydia:
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Chlamydia trachomatis grows in epithelial cells of the eye and genital mucosa
The infected epithelial cells then release inflammatory mediators and chemokines to trigger
influx of WBCs, eventually leading to cell mediated immunity
The chronic inflammation developing then causes epithelial cell necrosis, fibroblast
proliferation, and eventual scar formation
So damage from chlamydia comes from our immune response to get rid of it
Early stages of chlamydia infection show subtle symptoms or are asymptomatic, making spread
to other people very common
In women, the endocervix can be red and friable with mucus exudate that is less purulent than
that of gonorrhea
In men there can be a small amount of mucus urethral exudate
Chlamydia types D-K are not invasive and don’t penetrate or invade the submucosa, and instead
remain at the lumen surface of the epithelium and spread up the GU tract
Infections in women progress from the cervix (cervicitis) to the endometrium (endometritis),
to the fallopian tubes (salpingitis), to the peritoneum
In men with urethral infection (urethritis), chlamydia can eventually spread to the epididymis
(epididymitis) and prostate (prostatitis), but rarely ever the testicles
1/3 of patients end up getting Reiter syndrome – urethritis, arthritis, and conjunctivitis
o These people usually have HLA-B27
Chronic or repeated infection cause tubal infertility and PID
o These damages are irreversible, even after you remove the chlamydia
o This can put the woman at risk for life-threatening ectopic pregnancy
Infants born vaginally to infected moms can get elementary bodies in their eyes, ears, nose, and
mouth, causing them to develop conjunctivitis, or pneumonia characterized by a chronic
repetitive cough without wheezing
o The pneumonia symptoms show up at 4-11 weeks old, & only has moderate symptoms
o May show tachypnea and rales, but no wheezing
o Half of infected babies have conjunctivitis
LGV from chlamydia trachomatis can enter small breaks in skin and rarely cause a subtle genital
papule or ulcer – these patients are usually asymptomatic
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LGV can also cause rectal ulcers, rectal bleeding, rectal pain, and discharge
LGV can then lead to enlargement and ulcerations of the external genitalia, and lymphatic
obstruction that leads to elephantiasis of the genitalia
Chlamydophilia pneumonia is a common cause of atypical pneumonia
o Chlamydophilia pneumonia elementary bodies are spread by respiratory secretion
o Respiratory infections are usualy mild or asymptomatic
o Symptoms include pharyngitis, laryngitis, bronchitis, sinusitis, otitis media, or
pneumonia
o Chlamydophilia pneumonia infections can lead to asthma or make asthma worse
o Chlamydophilia pneumonia can infect and multiply in epithelial cells, endothelial cells,
monocytes, macrophage, lymphocytes, and cells involved in atherosclerosis
o Chlamydophilia pneumonia can add to coronary artery disease, and atherosclerotic
lesions in these people often have organism in them
 The chlamydophilia pneumonia stimulate inflammatory events that are
consistent with atherosclerosis
Chlamydia trachomatis and chlamydia pneumonia are similar in that the initial infections are
often mild or asymptomatic, & can lead to chronic infections that cause chronic inflammation
o Unlike them, the invasive LGV and chlamydophilia psittaci cause acute and sometimes
life-threatening illness
Inhalation of chlamydophilia psittaci from fecal aerosols of stressed or sick birds will initially
cause an abrupt flu-like illness that can rapidly progress to severe pneumonia
o Rarely, it can lead to hepatitis, endocarditis, and/or encephalitis
The most common way to diagnose chlamydia trachomatis is with nucleic acid amplification tests
(NAATs), like PCR, ligase chain rxn, or transcription-mediated amplification
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NAATs let you be noninvasive, and can work from urine samples
You want to swab mucosal epithelial cells, since the infection is usually intracellular, and
definitely swab discharges
Antimicrobial treatment of chlamydia needs something that is awesome at getting into the cells in a
high concentration for a long time, because chlamydia is intracellular and slow-growing
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Includes macrolides like azithromycin, doxycycline, and erythromycin (when doxycycline is
contraindicated in pregnant women and kids)
Treating won’t affect the elementary bodies, it only effects the metabolizing reticulate bodies
Like gonorrhea, you need to trace down the partners of those infected and test and treat them