- The advance of molecular biology the techniques like PCR, Southern blotting, gene cloning and DNA sequencing provided a good understanding of many infectious disease and genetics of other organisms.
OBLIGATE AND FACULTATIVE
INTRACELLULAR PATHOGENS
Intracellular pathogens are can be divided into two grouped :
- obligate intracellular or facultative intracellular . Obligate intracellular pathogens are those organisms that they lost their ability to live outside the host cell example for these group is all viruses , protozoa and bacteria such as Chlamydia and Rickettsia spp.
- Facultative intracellular pathogens are those organisms that can retain their ability to replicate outside their hosts , such as so many pathogenic bacteria and fungi.
- There are a suggestion that a loss in one gene differentiated between obligate and facultative pathogens which accompanies association of hosts and dependence.
- The distinguish between obligate and facultative pathogens can be done through their acquisition means in which obligate pathogens can be acquired only from other hosts , while facultative pathogens can be acquired from either other hosts or directly from environment.
- The relation ship of obligate intracellular pathogens to their hosts are dependent , in such way that they adapted to escape from host response mechanism , but when response of host mechanism occurs the microbial disease will cause by the disruption of that relation ship.
- There are varied relation ship between facultative intracellular pathogens to their hosts , some cause disease in a minority of hosts that infected which is related to transmission of infection , while others no needs for virulence of the hosts in their replication and survival.
Chlamydia and Reckittsia
Two obligate intracellular pathogens :
Chlamydia
Chlamydia are small obligate intracellular parasites , Gram Negative, ATP parasite bacteria. That contains DNA, RNA and ribosome which allows them to make their own proteins and nucleic acids, they have inner and outer membrane with lipopolysaccharide but not peptidoglycan in it.
There are three species which cause disease to human :
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C. trachomatis : which cause trachoma , Conjunctivitis , urogenital infections , lymphogranuloma venereum and pneumonia .
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C. pneumoniae : which cause pneumonia , bronchitis and sinusitis
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C. psittaci : which cause pneumonia
Chlamydia has two forms of phase :
- Elementary bodies (EB) : Extracellular form
- Reticulate bodies (RB) : Intracellular form
Table 1 . The difference between EB and RB can be explained as the following:
Life cycle of Chlamydia is between 48 – 50 hrs :
Figure 1. Developmental cycle of Chlamydia ( Beatty et al. 1994b)
Chlamydia have a unique two phase in developmental cycle : Extracellular within which infection to host cell occurs , is called elementary body ( EB ) , and Intracellular, within which replication inside the host cell occurs , is called reticulate body ( RB ).
The infection starts when EB attaches to host cell membrane , then it gets inside the cell by receptor-mediated endocytosis or parasite-specified phagocytosis , and when its inside the cell it will be surrounded by intracellular vacuole which protect them from lysosomal fusion and destruction .
Then EBs is differentiate into active RBs by using host cell energy and nutrition. Then RBs start binary fission for several rounds then it transform back into EBs, which is released to surrounded environment by exocytosis or host cell lysis.
Pathogenesis
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Chlamydial species infect different types of cells , C. pneumoniae infects and multiply inside human smooth muscle cells , endothelial cells , Monocytes /macrophages and lymphocytes in vitro. Chlamydia pneumonia spreads through mice system such as lung , spleen and macrophages. (Kaukoranta-Tolvanen et al. 1994, Gaydos et al. 1996, Fryer et al. 1997, Airenne et al. 1999, Haranaga et al. 2001).
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Reinfection with Chlamydia in the same host is common because the defense mechanism cannot provide protection from reinfection , in other word the defense mechanism in a host is unable to eradicate it. (Ward 1995).
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There is typicall association between chronic upper genital tract infection with an enhanced immune reaction (Peeling & Mabey 1999)..
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Serum antibodies and T-cell responses to some Chlamydial infection such as pelvic inflammatory disease , blinding trachoma ..etc (reviewed in Kinnunen et al. 2001).
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both chlamydial and human Hsp60 proteins are localized in atherosclerotic plaque macrophages (Kol et al. 1998)
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Chlamydia pneumonia induce oxidation of LDL in monocytes which result in cell foam formation . (Kalayoglu et al. 1999).
Figure 2: shows the Chlamydial infection : pathogenesis
{ Epicellular: Mycoplasmataceae and obligate intracellular bacteria:
Iren Budai MD , Semmelweis University }
Table 2. Acute and chronic diseases associated with C. pneumonia
Diagnosis
There are several laboratory diagnosis technique for detecting Chlamydia pneumonia which is shown in the table below.
Table 3. Laboratory methods for diagnosing C. pneumoniae infection
Treatment :
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. Azithromycin and clarithromycin , they both have highly activity against Chlamydia invitro. (Agacfidan et al. 1993, Welsh et al. 1996).
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fluoroquinolones and ketolides (Roblin & Hammerschlag 1998, Strigl et al. 2000, Miyashita et al. 2001a, Miyashita et al. 2002).
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Ampicillin and Penicillin , they not destroy the organism , they only prevent the growth of it(Kuo et al. 1995).
Rickettsia
Rickettsiae are small obligate intracellular , Gram Negative , coccobacilli , aerobic parasites of host cells. They will be inside cytoplasm or nucleus of the cell that they invade . their replication is by binary fission , they have G-ve cell wall with No Flagella .They have very small genome size which about 1.0 – 1.5 million base.
Figure 3. Taxonomic classification of the order Rickettsiales
{ © 2008 Kenneth Todar University of Wisconsin-Madison Department of Bacteriology}
Table 4. showing different type of disease cause by different species of Rickettsia
Life cycle of Rickettsia
The first step in Rickettsia pathogenesis is adhesion to the host cell when its inoculated to the skin by the bite of ticks or from the feces of flease to the damaged skin. As soon as it penetrate the skin it will be moved into blood stream which then infect the vascular endothelial cell . The adhesion occurs through the protein A at the outer membrane of Rickettsia this has been shown by blocking adhesion throught antibody to outer membrane proten A .
Then the second step will be Invasion of host cells , which is occurs by phagocyting Rickettsia by the cells , once its phagocuted it will move to the cytoplasm .
Then it will multiply and disrupt the host cell by lysing cell wall and release .This is occurs in Typhus group rickettsiae , while in Spotted fever group rickettsiae they do not lyse the cell wall , they release to outside the cell by stimulating polymerization of actin tails that derived from host cell which pass them through protoplasm to the membrane tips from which they emerge.
Diagnosis
There is no laboratory assay for rapid detection on early Rocky Mountain spotted fever .
Serologic assay is frequently used for confirmation of the Rocky Mountain spotted fever , the standard serological test which is use for detection of Rocky Mountain spotted fever is The indirect immunofluorescence assay (IFA) .
Immunostaining is another method which is use for diagnosis of Rocky Mountain spotted fever , this can be done by taking aswap from the rash of infected patient before starting therapy or within the first 48 hrs of starting therapy . The sensitivity of this test is only 70% in the laboratories that’s it cannot detect the agent always because Rickettsiae are distributed focally in lesions.
Treatment
- Tetracycline for the first 4- 5 days
- Doxycycline :100 mg every 12 hours for adults and for children is 4 mg/kg .
Reference:
- Annu. Rev. Microbiol. 2008. 62:19–33
- Evolution of Intracellular Pathogens by NESLi2 on 10/12/08.
- Experiments in Molecular Biology By Zachary F. Burton, Jon Masato Kaguni
A hitchhiker’s guide to cell biology: exploitation of host-cell
- functions by intracellular pathogens’ By Susanne M Rafelski and Julie A Theriot
- MOBILE DNA IN OBLIGATE INTRACELLULAR BACTERIA By Seth R. Bordenstein* and William S. Reznikoff*
- http://askabiologist.asu.edu / Guruatma "Ji" Khalsa, M.N.S.
- Chlamydia pneumoniae infection, inflammation and heat shock protein 60 immunity in asthma and coronary heart disease
- Prev Chapter 2. Review of the literature
- Murray et al. Medical Microbiology, 3rd Ed., Chapter 44
-
By Kenneth Todar University of Wisconsin-Madison Department of Bacteriology
- Epicellular: Mycoplasmataceae and obligate intracellular bacteria:Chlamydiaceae, Rickettsiaceae,Anaplasmataceae, Coxiellaceae By Iren Budai MD
Semmelweis University , Institute of Medical Microbiology
