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Chlamydia & Mycoplasma
Lecture 46 (Wed 09.23.09)
31
Medical
Professional
09/23/2009

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Cards

Term
what are some general characteristics of chlamydia?
Definition
  • gram negative
  • obligate intracellular
  • unique developmental cycle
  • ubiquitous/small size
Term

describe the intracellular developmental cycle of chlamydia.

Definition
  • the dense, infectious spore-like EBs are taken up in vacuoles ("inclusion") and enter the cytosol of infected cell
  • after internalization, EB differentiates into larger, less dense RB
    • nucleoid reorganizes into disperse config with permeable outer membrane allowing for nutrient uptake
  • RB is metabolically active, multiplies intracellularly by binary fission; actively transports metabolites/precursors from cytosol of infected cell; multiplies while in contact with membranous vacuole wall
  • late differentiation occurs 20-40hrs post infection when late expressed genes mediate outer membrane rigidification and condensation of chromosomal DNA
  • fully mature condensation may have 100s-1000 EB; also may be >1 inclusion per cell; inclusions may be lobar
  • cycle over when inclusion and host cell lyse and the progeny EB go on to infect neighboring cells in the same host or are transmitted to a new host
Term

at any given time inside an inclusion, are bodies at the same stage of differentiation?

Definition

no. there is asynchronous differentiation.  during late stage differentiation in the mature inclusion there are many EBs and fewer RBs that have yet to convert to EBs.

Term

describe some of the major differences between EB vs RB

Definition
  • EB
    • smaller diameter
    • denser; compact DNA with histones
    • late stage of differentiation
    • strong cell wall (cysteine rich, lots of disulfides)
    • no metabolism, no replication
  • RB
    • opposite of the above
    • made to replicate!!
    • not infectious
    • larger, less dense
    • pleitrophic cell walls (more diversity)
    • highly infectious
Term
briefly describe chlamydia genomics
Definition
  • small genome (1-1.2million base pairs) that is highly conserved among species (800/1000 genes shared)
  • low G+C (~40%)
  • no repeat sequences
  • one of the easiest genomes for sequencing
  • shattered dogmas:
    • chlamydia can make some ATP
    • chlamydia have peptidoglycan
Term

what are some important chlamydia virulence factors?

Definition
  • non specific adherence
  • tryptophan synthase
  • Type III secretion: molecular "syringes" that inject virulence factors directly into the cytosol of infected cells
  • cytotoxins related to clostridial cytotoxins
Term
how does severe disease result from chlamydia infection?
Definition
  • primary infection is usually localized to the site of infection; frequently asymptomatic or a mild nuisance; usually easily treated with broad spectrum antibiotics
  • pathology results from inflammatory response (infected host cells release chemokines and proinflammatory cytokines that provoke inflamm cascade)
  • severe disease from chronic infection & disease sequelae from extensive tissue remodeling and scarring, usually years post-primary infection, and at site remote from that of the initial one
Term

what serovars cause the primary infection in trachoma?

Definition
  • serovars: A, B, C
  • trachoma: world's leading cause of blindness
  • primary infection:
    • inclusion conjunctivitis (starts in babies w/in weeks of birth; spread from siblings or house flies)
  • then more chronically (in teenage yrs):
    • follicular conjunctivitis
  • corneal inflammation and scarring in adult years leads to:
    • pannus (scarring & neovascularization)
    • contraction of conjuctiva leads to in-turned eyelashes
    • continuous corneal abrasions from eyelashes leads to
      • trichiasis (corneal scarring)
      • blindness (in mid to late adulthood)
Term

in what populations does inclusion conjunctivitis develop?

Definition
  • infants: during passage through infected birth canal, demonstrating that serovars predominant in one tissue can infect another tissue type/site
  • adults: with genital infection or infected partners
Term

what are two potential chlamydial infections of the newborn?

Definition
  1. ophthalmia neonatorum
    • incubation: 5-12 days post-natal
    • hospitals require antibiotic eyedrops immediately after delivery
  2. pneumonia syndrome of newborn
    • incubation: 3-16 weeks
    • interstitial pneumonitis
    • chronic, if untreated
Term

what is treatment for chlamydial infections of the newborn?

Definition
  • erythromycin base 50mg/kg/day for 14 days
  • macrolides, less data but probably equally effective
Term
what serovars are responsible for chlamydial STI?
Definition

predominantly caused by serovars D-K

 

  • most common bacterial STI in US
  • 10% sexually active population is infected
  • highest incidence in adolescents
  • most often asymptomatic or mild, hence it being unreported or untreated
  • men = reservoirs
Term
how may chlamydia present in men?
Definition
  • non-gonococcal urethritis (NGU)
  • epididymitis
  • men are more often asymptomatic, thusly functioning as reservoirs for bacteria
Term
how may chlamydia present in women?
Definition
  • urethritis
  • cervicitis (majority asymptomatic)
  • salpingitis
  • pelvic inflammatory disease (PID)
  • possible sequelae include:
    • infertility
    • life-threatening ectopic pregnancy
Term

what are some sequelae of chronic C.pneumoniae infection?

Definition
  • chronic bronchitis
  • asthma
  • exacerbation of COPD
Term

what are some sequelae of *disseminated* chronic C.pneumoniae infection?

Definition
  • reactive arthritis
  • abdominal aortic aneurysm
  • stroke
  • MS, alzheimer disease
  • strongest association with artherosclerosis
Term

what is the relationship between CVD and C.pneumoniae?

Definition
  • viable C.pneumoniae has been found in atherosclerotic plaque of CHD patients
  • large antibiotic intervention studies aimed to demonstrate a causal role of C.pneumoniae infection in the devt of CHD=  in humans INCONCLUSIVE
  • animal models (mice, rabbits) show C.pneumoniae does contribute to devt of atherosclerotic plaques and that it can be recovered in pure culture from diseased arteries
Term

how is diagnosis and treatment of C.pneumoniae handled?

Definition
  • diagnosis
    • not usually attempted because organism if fragile and difficult to culture
  • treatment
    • doxycycline or erythromycin for at least 10 - 14 days
    • quinolones (ie: levofloxacin)
  • no vaccine
Term

what strain of chlamydia is an occupational hazard to people exposed to exotic birds, poultry farm workers, and BGE engineers & what is the treatment?

Definition
  • avian Chlamydia psittaci

psittacosis (ornithosis): zoonotic infection caused by C.psittaci EBs in feces of infected animals

 

flu-like illness --> severe pneumonia-like syndrome

 

treatment: DOXYCYCLINE, TETRACYCLINE

 

30-95% infection rate in pigeons in Sarajevo, chicken in Beijing

 

outbreaks in "foie gras" duck farms in France, poultry in Germany

Term
what is mycoplasma?
Definition
  • wall-less pleiomorphic bacteria, evolved from Gram-positive by mutational loss
  • able to grow outside of host cell
  • broad group, few pathogenic to humans
  • fastidious organisms, difficult to manipulate in vitro
Term

what species of Mycoplasma cause disease in humans?

Definition

 

  •    Mycoplasma pneumoniae
  •   Mycoplasma hominis
  •   Mycoplasma genitalium
  •   Mycoplasma fermentens
  • Ureaplasma urealyticum

 

Term

what cellular characteristics led to mycoplasma's being mistaken for a virus?

Definition
  • small size and plasticity of mycoplasma (since it doesnt have a cell wall) allow these to pass through verrrry  small pores
  • "filtrability" along w/ poor biochemical and electron microscopy data led to their wrong characterisation as viruses
  • also- they are difficult to manipulate in vitro (complex nutritional requirements), grow at slow rates (2-8 hour generation time), and usually yield tiny colonies on agar that are visible in 3-10 days
Term

how do mycoplasmas replicate and what is their colony morphology?

Definition

1) binary fission to form chains

 

or

 

2) cell elongation to eventually split into multiple cells

 

colony morphology: "fried egg" for most mycoplasmas; an important exception is M.pneumoniae, which forms mulberry colonies

Term

what are some potential mycoplasma virulence determinants?

Definition
  • hemolysins
    • alpha or beta
    • M.pneumoniae makes beta
    • all other human mycoplasmas make alpha
  • surface structures
    • attachment organelles (M.pneumoniae) that mediate attachment to the surface of ciliated epithelial cells of resp. tract
  • capsule
    • some species make polysaccharide capsule that may be involved in attachment or may have toxic effects
Term

primary, atypical pneumonia may be of multiple etiologies. name some causative agents.

Definition
  • Legionella pneumophila
  • adenovirus
  • influenza A and B viruses
  • parainfluenza type 3
  • RSV
  • M.pneumoniae *** only agent causing primary atypical pneumonia that is associated with cold aglutinins
Term

what is the epidemiology and clinical presentation of M.pneumoniae?

Definition
  • 2 million cases/yr in US
  • leading cause of pneumonia in school-age children and young adults
  • clinical presentation:
    • persistant dry cough
    • "scratchy" sore throat
    • malaise
    • low fever
    • community acquired
    • frequently referred to as "walking pneumonia"
  • diagnose via serology and PCR
Term

what are the beneficial and deleterious immune responses in M.pneumoniae infection?

Definition

beneficial

  • early on IgM Abs
  • later in infection IgG Abs
  • no long lasting protection (IgM, IgG)
  • IgA in resp secretions and CMI play a role in host resistance

deleterious

  • 1/2 half pts develop "cold agglutinins": IgM Abs agglutinate RBCs at 4 degrees C, but not at 37 degrees C
  • these IgM are specific to one host RBC antigen thats on surface of 97% folks' RBCs
  • theory: during infection some RBC Ags damaged, self recognition is lost, and so they are readily attacked by IgMs --> autoimmune response
  • human brain glycolipids cross-react with Abs to M.pneumoniae --> CNS complications

 

Term
how is M.pneumoniae diagnosed?
Definition
  • round mulberry colonies
  • serology is method of choice
    • cold agglutinins (old test, poor sensitivity)
    • IgG or IgM by ELISA
  • culturing is SLOW (~20 days) and requires a complex isolation medium
Term
how is M.pneumoniae treated?
Definition
  • doxycycline
  • ciproflaxin
  • erythromycin
  • azithromycin
  • levoflaxin

no vaccine

Term

what mycoplasma are present in the genital tract of a large proportion of sexually active adults?

Definition

M. hominis, M. genitalium & U. urealyticum

even present in the absence of disease, and so must usually behave as part of normal flora; on rarer occasions they appear to be part of the etiology of PID along w/other pathogens

Term

HIV grows better in vitro when host cells are already infected with what species of Mycoplasma?

Definition

M. fermentans or M. penetrans
why? potential possibilities for this finding are:
-mycoplasma are opportunistic infections themselves
-mycoplasma infection enhaces HIV virulence as in in vitro experiments
-AIDS-associated mycoplasma are pathogenic in their own right

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