Trypanosoma cruzi trans-sialidase as a new therapeutic tool in the treatment of chronic inflammatory diseases: possible action against mycoplasma and chlamydia

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Abstract

The present paper proposes a new therapy using Trypanosoma cruzi trans-sialidase to treat diseases with unclear pathogenesis that present in common chronic inflammation and fibrosis. This hypothesis is based on recent findings that co-infection with mycoplasma and chlamydia is present in many of these diseases and that this enzyme was capable to eliminate or decrease the co-infection from the host. We identified that mycoplasmas and chlamydias are present in atherosclerosis, aortic valve stenosis, dilated cardiomyopathy, chronic chagasic myocarditis and cancer. We hypothetized that mycoplasmal infection may induce immunodepression in the host, favoring proliferation of pre-existent chlamydial infection and that elimination of mycoplasma would lead to improvement of the immune system resistance and the control of chlamydial proliferation. Mycoplasma has a particular parasitic relationship with host cells, involving strong adherence of their membranes, making it extremely difficult to eradicate mycoplasmal infection from the host. A new therapeutic approach is suggested using one or more agents that prevent or inhibit the adherence of mycoplasma to host cell membranes by removing sialic acid residues and preventing oxidation of the cells. The use of a neuraminidase enzyme, particularly the T. cruzi trans-sialidase enzyme, associated with treatment using anti-oxidating agents is proposed. Preliminary experimental animal and laboratory tests showed good results. The proposal that trans-sialidase from T. cruzi is efficient in combating co-infection of mycoplasma and chlamydia is based, at least in part, on the observation that chagasic patients suffering from T. cruzi infection present less mycoplasma and chlamydia infection in their tissues. Also, a lower incidence of the diseases above described to be related to mycoplasma infection is observed in chagasic patients. It is also hypothesized that co-infection with mycoplasma and chlamydia may induce oxidation of the host cells. Anti-oxidants such as those present in plant extracts may also be used in the treatment. Other diseases such as chronic hepatitis, glomerulonephritis, Multiple Sclerosis, Alzheimer's Syndrome and idiopathic encephalitis are other examples of chronic diseases where mycoplasma and chlamydia might be present, as they have the characteristics of unknown etiology, persistent chronic inflammation and fibrosis.

Section snippets

A possible role for co-infection with mycoplasma and chlamydia in the pathogenesis of chronic inflammatory diseases

Many chronic degenerative, autoimmune and neoplasic diseases have been shown to possess related factors in the mechanisms of lesion that are common such as: chronic inflammation, fibrosis, increase of free radicals (oxidation) [1], [2], [3], lack of NO production, increase of NFκB and TNF [4], [5], and increase of LDL in the serum. Diseases apparently having no relationship such as Alzheimer Syndrome, Multiple Sclerosis, “mad cow disease”, cancers, atherosclerosis, idiopathic arthritis,

Relationship between co-infection with Mycoplasma pneumoniae and Chlamydia pneumoniae versus inflammation and atherosclerotic plaque vulnerability [23]

Vulnerable atherosclerotic plaques are rich in oxidized lipids and in foam cells [24], which have a fundamental role in development of inflammation, rupture and thrombosis of the plaque [25]. We detected large quantities of Mycoplasma pneumoniae (MP) and Chlamydia pneumoniae (CP) in atheromas of coronary arteries, much greater than the numbers found in stable ones [26], [27]. This may be not surprising as mycoplasma is the only bacterium that needs cholesterol for survival and proliferation [28]

The role of sialic acid in mycoplasmal virulence

Mycoplasmas do not possess an external cell wall. They adhere to the external surface of the host cell via strong association with the cell membrane. Apparently, attachment to the host cell is the first step in colonization of target tissues and seems to be a requirement for infection [39].

Interference in this first step may be fundamental in the control of mycoplasma infection, since current antibiotics show low effectiveness in this regard as they neither prevent attachment, nor remove the

Final considerations

The present work is a summary of recent findings from our lab that strongly suggest that mycoplasma and chlamydia participate in the pathogenesis of certain chronic inflammatory diseases and that the use of T. cruzi trans-sialidase may be effective as a new therapeutic approach for the treatment of these diseases. The use of anti-oxidants as for example extract from plants is also useful in controlling of such-co-infection.

Other diseases such as chronic hepatitis, glomerulonephritis, the

References (49)

  • J.S. Ross et al.

    Atherosclerosis and cancer. Common molecular pathways of disease development and progression

    Ann. NY Acad. Sci.

    (2001)
  • G. Valen et al.

    Nuclear factor kappa-B and the heart

    J. Am. Coll. Cardiol.

    (2001)
  • G.C. Giles et al.

    Androgenic alopecia and prostate cancer: findings from an Australian case-control study

    Cancer Epidemiol. Biomarkers Prev.

    (2002)
  • C. Wolfson et al.

    Bacterial infection as a cause of multiple sclerosis

    Lancet

    (2002)
  • J. Danesh et al.

    Chronic infection with Helicobacter pylori, Chlamydia pneumoniae, or cytomegalovirus: population-based study of coronary heart disease

    Heart

    (1999)
  • D.G. Haegert

    The initiation of multiple sclerosis: a new infectious hypothesis

    Med. Hypoth.

    (2003)
  • A. Ricco

    Prion: toxic or infectious agent

    Med. Hypoth.

    (2003)
  • G. Zanusso et al.

    Detection of pathologic prion protein in the olfactory epithelium in sporadic Creuzfeldt–Jacob disease

    N. Engl. J. Med.

    (2003)
  • A.P. Burke et al.

    Elevated C-reactive protein values and atherosclerosis in sudden coronary death. Association with different pathologies

    Circulation

    (2002)
  • B. Fuhrman et al.

    Flavonoids protect LDL from oxidation and attenuate atherosclerosis

    Curr. Opin. Lipidol.

    (2001)
  • M. Almagor et al.

    Role of superoxide anion in host cell injury induced by M. pneumoniae infection. A study in normal and trisomy 21 cells

    J. Clin. Invest.

    (1984)
  • G. Ben-Menachem et al.

    The thiodoxin reductase system of mycoplasmas

    Microbiology

    (1997)
  • A. Blanchard et al.

    AIDS-associated mycoplasmas

    Annu. Rev. Microbiol.

    (1994)
  • O. Grau et al.

    Association of Mycoplasma penetrans with human immunodeficiency virus infection

    J. Infect Dis.

    (1995)

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