Instituto Valenciano de Microbiología

Masía El Romeral
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46117 Bétera (Valencia)
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Mycoplasma fermentans: Respiratory and genitourinary infections - Molecular diagnosis (PCR); Species identification (PCR and sequencing).

Information 24-06-2018.

Mycoplasma fermentans is a small Gram negative microorganism with no cell wall that causes respiratory and genitourinary infections in humans. The isolation in culture of this microorganism from clinical samples is difficult, and with the development of molecular techniques (PCR) the presence of M. fermentans has been associated with a large number of diseases, suggesting its involvement in rheumatoid arthritis, and its possible action as cofactor of AIDS, among others. However, these associations are still being studied, and at present, the pathogenicity of this microorganism in humans is not completely known.

Mycoplasmas belong to the Mollicutes class and are the smallest self-replicating eubacteria. They are devoid of cell wall and surrounded only by a plasma membrane. They have a small genome, which varies from 580 to 1380 kbp, and which results in limited metabolic capacities and parasitism. Mycoplasmas can be found as parasites in a wide range of hosts, including humans, animals, insects and plants. In addition, they are frequent contaminants of cell cultures. In humans, some species of Mycoplasma are found as commensal inhabitants, while others are associated with infectious diseases and post-infection pathologies. Most of the known Mycoplasma species are found as parasites on the surface of the membrane. They exhibit strict host and tissue specificities, and depend on adherence to host tissues for subsequent colonization and infection. In addition, some Mycoplasma species penetrate cells and become intracellular residents.

Mycoplasmas can cause chronic infections due to the development of sophisticated mechanisms to evade the immune response by means of molecular mimicry, and to regulate ascending or decreasing cytokine secretion, the expression of adhesion molecules, the expression of transcription factors, apoptotic pathways and the activity of MAP kinases, among others. In addition, different studies strongly support the ability of Mycoplasma to cause or promote oncogenic transformation, and currently, the link between Mycoplasma spp. and cancer is being investigated.

Mycoplasma fermentans is a human pathogen that was isolated for the first time in the 1950s in the urogenital tract of men and women. Although it was initially believed that humans were natural hosts, M. fermentans has also been isolated from genital lesions in sheep. It is an invasive mycoplasma, which colonizes the tissues of the human mucosa of healthy adults and, under certain conditions, can invade host cells thanks to the secretion of the enzyme tyrosine phosphatase, which participates in the process of internalization. It has also been isolated from various tissues and its apparent dissemination depends on the host's defense mechanisms, being more vulnerable the patients with leukemia, AIDS and patients with treatments with immunosuppressive drugs. However, it has been reported that dissemination may also occur in hosts with a competent immune system. The presence of Mycoplasma fermentans has been detected in the pharynx, peripheral blood leukocytes, synovial fluid and urine.

Among the known virulence factors of M. fermentans are organelles for adhesion and cell penetration, the secretion of enzymes such as tyrosine phosphatase, the secretion of exonucleases to destroy the nucleotides of the host cell, and the presence of lethal protein fractions. Also, to evade the immune response of the host and go unnoticed, this mycoplasma makes variations in phase and size in the main antigens and lipoproteins of its membrane surface. In addition, M. fermentans has an immunomodulatory effect on the individual's immune system causing polyclonal activation of immune cells, increased cytotoxicity of T cells, and the induction of expression and secretion of a wide variety of cytokines. Finally and as mentioned, this mycoplasma has intracellular penetration capacity with cytoplasmic and perinuclear distribution in a wide range of human cell types. Likewise, it has been shown that M. fermentans induces the expression of oncogenes.

Mycoplasma fermentans causes respiratory and genitourinary tract infections in men and women, besides producing infectious pathology that affects pregnancy, delivery, fetus and neonate. Interest in this organism has recently increased due to its possible role in the pathogenesis of chronic inflammatory diseases, such as rheumatoid arthritis, chronic fatigue syndrome, fibromyalgia and neurological diseases. This mycoplasma has been detected in the blood and synovial fluid of patients with rheumatoid arthritis and other inflammatory arthritic disorders. In addition, it has been shown that M. fermentans causes a significant inhibition of TNFα-induced apoptosis in human cells in vitro, reinforcing the hypothesis that this microorganism could play a pathogenic role in the development of diseases characterized by altered apoptosis, such as rheumatoid arthritis. However, its relationship with the disease is not completely clear to this day. Other studies also reported the presence of M. fermentans in blood samples from patients with the Gulf War Syndrome and Chronic Fatigue Syndrome, although this last statement has been refuted. Finally, different studies suggest that this organism could be one of the mycoplasmas that could function as a cofactor that accelerates the progression of the human immunodeficiency virus disease. It has been suggested that mycoplasmas may play a role as cofactors in one of the early stages of the life cycle of lentiviruses and promote disease in HIV-infected patients, and M. fermentans has been detected in blood and urine samples from patients with HIV and AIDS. Supporting this theory, in vitro studies have reported that coinfection with M. fermentans significantly increases the ability of HIV-1 to induce cytopathic effects on human T lymphocytes.

The microbiological diagnosis of infections caused by mycoplasmas has always been limited by the very difficult growth of these microorganisms, the lack of commercialized culture media, the absence of rapid diagnostic procedures and the widespread clinical perception that these microorganisms are less important. in the context of infectious diseases. This situation has changed markedly in recent years thanks to the commercialization of culture media, the development of rapid serological diagnostic techniques and, especially, the application of nucleic acid amplification methods, marketed or developed in the laboratory itself. Among the mycoplasmas, M. fermentans is considered a relatively annoying species. This mycoplasma is typically grown in SP4 medium. However, although this species is a common contaminant of cell lines, isolation in culture from clinical material is rare. The role of M. fermentans in human pathology may have been underestimated because culture is performed infrequently in routine laboratories. In recent years, with the application of molecular methods (PCR) for the diagnosis of M. fermentans, this microorganism has been implicated in a variety of clinical conditions in humans, the majority of which are pending confirmation.

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