BB PELOTTAVA TAUDINAIHEUTTAJA

[Bb]

Lähettäjä: Soijuv Lähetetty: 19.11.2005 12:22

Arvostetussa lääketieteellisessä julkaisussa Lancetissa oli juuri usean lääkärin/tutkijan kirjoittama artikkeli borrelioosista ja siitä miten se aiheuttaa yhä kasvavia ongelmia. Borrelioosi on paljon monimutkaisempi tauti kuin kliinikot myöntävät. Tutkijat tietävät taudin/bakteerin monimuotoisuuden ja vaikeudet tuhota bakteeria, mutta tieto ei näytä vaikuttavan käytännön hoitoihin. 2 - 4 viikon antibioottihoito saattaa auttaa aivan akuutissa vaiheessa mutta ei pidemmälle edenneeseen tautiin.

Bb käyttää samanlaisia imnuunijärjestelmän "hämäystaktiikoita" kuin mykobakteerit, jotka aiheuttavat tuberkuloosia ja lepraa. Bb käyttää fibrinolyyttistä järjestelmää tunkeutuessaan keskushermostoon, Bb kykenee tunkeutumaan elimistön eri solujen sisälle, jonka vuoksi se on käytännöllisesti katsoen täysin suojassa esim. antibiooteilta, Bb kykenee elämään kuukausia kystamuodossa jne. Näin ollen bakteerin geneettinen monimuotoisuus, intrasellulaarinen sijainti, itsesäätely ja kyky paeta immuunijärjestelmää tekevät siitä pelottavan taudinaiheuttajan.


http://www.thelancet.com/journals/lance ... 5/fulltext

The Lancet 2005; 366:1771

DOI:10.1016/S0140-6736(05)67721-5

Lyme disease: scratching the surface

Steven E Phillips, Nick S Harris, Richard Horowitz, Lorraine Johnson and Raphael B Stricker email address <rstricker@usmamed.com>

The excellent Comment by Ulrike Munderloh and Timothy Kurtti (Sept 17, p 962)1 describes the complex life cycle of Borrelia burgdorferi, the spirochaetal agent of Lyme disease, as it traffics between tick and mammalian hosts. The Comment highlights a growing problem with Lyme disease: while what is known about the basic science of this tick-borne illness becomes more complex, the clinical science remains relatively simplistic and uninformed.2 This divergence has produced a disconnection between the recognition of B burgdorferi as one of the most invasive and elusive bacteria known to man, and the clinical perception that Lyme disease is ?hard to catch and easy to cure?.

Bb:ssä on vähintään132 toimivaa geeniä, 21 plasmidia (enemmän muin missään muussa tunnetussa bakteerissa)
The complexity of the Lyme disease spirochaete goes beyond the features described by Munderloh and Kurtti. With more than 1500 gene sequences, B burgdorferi contains at least 132 functioning genes; by comparison, the spirochaetal agent of syphilis, Treponema pallidum, contains only 22 such genes.2 Furthermore, the Lyme disease spirochaete contains 21 plasmids (nine circular and 12 linear).2 This is by far the largest number of plasmids found in any known bacterium, and the large number of plasmid genes is thought to provide a rapid response system that allows the spirochaete to cycle efficiently between ticks and mammals.3 Gene exchange and plasmid transfers among Borrelia strains can also increase the pathogenicity of the organism.3
In the mammalian milieu, B burgdorferi uses the host fibrinolytic system to penetrate the blood-brain barrier and gain access to the central nervous system. The Lyme disease spirochaete contains a secretory mechanism for porin, adhesin, and haemolysin proteins, and these secreted products can contribute to the invasive properties of the organism.4 The spirochaete can enter cells such as fibroblasts, synovial cells, endothelial cells, and macrophages. In these cells, it becomes functionally resistant to treatment, partly due to ?camouflage? proteins produced by itself or adsorbed from the cell, and partly due to altered morphology as the spirochaete assumes a non-replicating cyst form.
The immune evasion strategy used by B burgdorferi is similar to strategies used by the mycobacterial agents that cause chronic infections such as tuberculosis or leprosy.2

These organisms also exist as non-replicating cyst forms that can be ?resuscitated? by autocrine cytokine-like factors after lying dormant for months. B burgdorferi has been shown to use luxS, an autoinducer gene used by other bacteria, to regulate replication.5 It is the first time that this autoinducer gene has been identified in a spirochaete. Thus the combination of genetic complexity, intracellular localisation, immune evasion, and autoregulation makes the Lyme disease spirochaete a formidable infectious agent.

By contrast with the complex basic science of B burgdorferi outlined above, a popular clinical notion is that Lyme disease can be cured with 2?4 weeks of antibiotics. Although this might be true of promptly treated acute B burgdorferi infection, chronic infection that allows the spirochaete's complex pathophysiological mechanisms to unfold can result in tenacious tissue invasion that is extremely difficult to eradicate. Understanding the pathophysiological complexity of this organism should help to improve our clinical approach to Lyme disease.

We declare that we have no conflict of interest.
References

1. Munderloh UG, Kurtti TJ. The ABCs of Lyme disease spirochaetes in ticks. Lancet 2005; 366: 962-964. Full Text | PDF (41 KB) | CrossRef

2. Stricker RB, Lautin A, Burrascano JJ. Lyme disease: point/counterpoint. Expert Rev Anti Infect Ther 2005; 3: 155-165.

3. Qiu WG, Schutzer SE, Bruno JF, et al. Genetic exchange and plasmid transfers in Borrelia burgdorferi sensu stricto revealed by three-way genome comparisons and multilocus sequence typing. Proc Natl Acad Sci USA 2004; 101: 14150-14155. MEDLINE | CrossRef

4. Cluss RG, Silverman DA, Stafford TR. Extracellular secretion of the Borrelia burgdorferi Oms28 porin and Bgp, a glycosaminoglycan binding protein. Infect Immun 2004; 72: 6279-6286. MEDLINE | CrossRef

5. Stevenson B, von Lackum K, Wattier RL, McAlister JD, Miller JC, Babb K. Quorum sensing by the Lyme disease spirochete. Microbes Infect 2003; 5: 991-997. MEDLINE | CrossRef

[Bb]

Lähettäjä: Sar_Ani Lähetetty: 23.11.2005 13:26

Uusi mielenkiintoinen tutkimus puolalaisilta!

Useat (mm. suomalaiset) tutkimukset ovat jo osoittaneet, miten borrelia pystyy suojautumaan complementtijärjestelmän hyökkäyksiltä (H-proteiini, jonka se sieppaa isännältään suojautuakseen). Uusi tutkimus paljastaa, että borrelia kantaa ulkokuorellaan myös scialic acidia, mikä puolestaan suojelee sitä puolustusjärjestelmän toisenlaiselta hyökkäykseltä, lecitin pathway.

Uusi puolalainen tutkimus:


1: Folia Microbiol (Praha). 2005;50(3):229-38. Related Articles, Links

Lectin-binding characteristics of a lyme borreliosis spirochete Borrelia burgdorferi sensu stricto.

Vancova M, Nebesarova J, Grubhoffer L.

Faculty of Biological Sciences, University of South Bohemia, Ceske Budejovice, Czechia.

Borrelial glycoconjugates were localized by labeled lectins on ultrathin cryosections and on surfaces of intact negatively stained bacteria. Protein-saccharide complexes in these glycoconjugates were partially characterized by means of enzyme deglycosylation and mild alkali pretreatment of cryosections. The results of labeling were examined by transmission electron microscopy. Statistically evaluated results (relative labeling index, chi2 test) of gold labeling indicated that surfaces of Borrelia burgdorferi strain B31 and external (outer) membrane vesicles (MVs) were covered with glycoconjugates containing O-glycosidically linked N-acetyl-D-galactosamine (GalNAc) and N-glycosidically linked N-acetyl-D-glucosamine (GlcNAc). The presence of N-linked GalNAc, sialic acid, mannose and fucose on the surfaces of outer membranes and MVs was probably due to an adherence of BSK-H medium components, especially rabbit serum, to Borrelia surfaces.

PMID: 16295662 [PubMed - in process]

Hieman vanhempi, samoilla jäljillä:


Zentralbl Bakteriol. 1992 Apr;276(4):473-80. Related
Articles, Links

Characterization of Borrelia burgdorferi glycoconjugates and surface carbohydrates.

Hulinska D, Volf P, Grubhoffer L.

Institute of Hygiene and Epidemiology, Prague.

Borrelia burgdorferi glycoconjugates with different oligosaccharide structures were characterized by a blotting technique with peroxidase- abelled lectins. The localization of surface carbohydrates was studied using electron microscopy with lectin-gold complexes. A high-mannose glycan structure was detected in 83 kDa glycoprotein (major extracellular protein); at least four carbohydrates (glucose or mannose, galactose, N-acetylgalactosamine and N-acetylglucosamine) were present in other Borrelia glycoconjugates.

N-acetylneuraminic (sialic) acid was detected on the Borrelia surface. Two sialidases with different specificities were used in an attempt to cleave off the Borrelia N-acetylneuraminic acid. The attempt was successful by using Vibrio cholerae sialidase which has a broad substrate specificity, while the mumps-virus sialidase with restricted substrate specificity had no effect. Endogenous activity of N-acetylneuraminidase was not demonstrated in B. burgdorferi K 5 and B 31 strains.

PMID: 1611204 [PubMed - indexed for MEDLINE]

MBL:n osuudesta puolustuksessa tiedetään toistaiseksi melko vähän.


1: Scand J Immunol. 2004 Jul-Aug;60(1-2):23-9. Related Articles, Links

The potential role of mannan-binding lectin in the clearance of self-components including immune complexes.

Saevarsdottir S, Vikingsdottir T, Valdimarsson H.

Department of Immunology, Landspitali-University Hospital, Hringbraut, 101 Reyjavik, Iceland.

Mannan-binding lectin (MBL) is a pattern recognition receptor in the innate immune system. It recognizes certain sugar residues arranged in a pattern that enables MBL to bind with sufficient strength. Such sugar patterns are common on the surface of many microorganisms, and MBL has therefore been considered to be an agent that can discriminate between self and nonself. There is, however, increasing evidence supporting that MBL, like many membrane-bound C-type lectin-like receptors, also helps to dispose of various outworn or abnormal body components. Most self-components are protected with sialic acid or galactose that disrupt the pattern of the sugars that MBL can bind, but MBL may be significantly involved in the elimination of self-components that have lost these protective terminal residues. The role of MBL in the clearance of invading pathogens has previously been thoroughly reviewed. Here, we review some findings that support the notion that MBL may contribute to noninflammatory removal of immune complexes and abnormal cells by the reticuloendothelial system. Defects in this clearance mechanism may cause an accumulation of potentially dangerous self-components, thereby increasing the likelihood of chronic inflammation and autoimmunity.

Publication Types:
* Review
* Review, Tutorial

PMID: 15238070 [PubMed - indexed for MEDLINE]