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Transcript
Micro Chapter 27: Chlamydiae: Genital, Ocular, and Respiratory Pathogens Chlamydia are obligate intracellular pathogens - 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” - 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 - 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 - 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 - Most common cause of preventable blindness in the world 70-90% of adults have been, or are infected with chlamydophila pneumonia - 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 - 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 - - - - - - 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 - 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: - - - 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 - - - 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 - 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 - 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