Detection of Mycoplasmas in Patients with Amyotrophic Lateral Sclerosis

Constantino Gil, Alma Aurora Sánchez González, Isidro Lecona León, Antonio Rivera, Rayo Santellán Olea, Lilia Cedillo

Centro de Investigaciones en Ciencias Microbiológicas, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Edificio 103J, Ciudad Universitaria, Col. San Manuel, Puebla Pue, México.
Escuela de Biología, Benemérita Universidad Autónoma de Puebla, Edificio 112A Ciudad Universitaria, Col. San Manuel, Puebla Pue, México.
Servicio de Neurología, Centro Médico Nacional Manuel ávila Camacho, IMSS, Puebla, México.

DOI: 10.4236/aim.2014.411077                

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a progressive degenerative disease of the motor neurons and the cause is unknown. Diverse factors such as genetic defects, nutritional deficiencies, head trauma, environmental toxin, autoimmune responses and viral and bacterial infections are involved. Mycoplasmas have been implicated as causal agents of different illnesses in human. The purpose of this study was to investigate the presence of mycoplasmas in the bloodstream of patients with ALS. Patients with ALS and healthy individuals were included in the study. A blood sample was taken in tubes with or without anticoagulant. Mycoplasmas were detected by culture or direct PCR, and the presence of antibodies IgM and IgG against LAMPs of these microorganisms by Western blot. Cultures for aerobic facultative bacteria were also done. Blood samples from 13 patients and 44 healthy individuals were screened. All blood cultures for non-fermentative mycoplasmas and aerobic facultative bacteria were negative. Cultures for fermentative mycoplasmas were considered positive after identification of mycoplasmal DNA by PCR. Mycoplasma sp. was detected by culture or direct PCR in 6/13 (46%) patients and in 4/44 (9%) of healthy individuals. M. fermentans was detected by PCR using specific primers in six patients and in two healthy individuals. IgM against LAMPs of M. fermentans were detected in 6/13 (46%) blood samples from patients and in 13/44 (30%) from healthy individuals, while. IgG was detected in 4/13 (31%) patients and in 3/44 (7%) healthy individuals. The results of this study show that mycoplasmas cause a systemic infection and could play a role in the origin or progression of the ALS.

Keywords

Amyotrophic Lateral Sclerosis, Mycoplasmas, Immune Response

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Hardiman, O., van den Berg, H.L. and Kiernan, C.M. (2011) Clinical Diagnosis and Management of Amyotrophic Lateral Sclerosis. Nature Reviews Neurology, 7, 639-649. http://dx.doi.org/10.1038/nrneurol.2011.153
[2]	Miller, R.G., Gelinas, D. and O’Connor, P. (2005) Amyotrophic Lateral Sclerosis. American Academy of Neurology, New York.
[3]	Brooks, B.R., Miller, R.G., Swash, M. and Munsat, T.L. (2000) El Escorial Revisited: Revised Criteria for the Diagnosis of Amyotrophic Lateral Sclerosis. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders, 1, 293-299. http://dx.doi.org/10.1080/146608200300079536
[4]	Kiernan, C.M., Vucic, S., Cheah, C.B., Turner, R.M., Eisen, A., Hardiman, O., Burrell, R.J. and Zoing, C.M. (2011) Amyotrophic Lateral Sclerosis. Lancet, 377, 942-955. http://dx.doi.org/10.1016/S0140-6736(10)61156-7
[5]	Pasinelli, P. and Brown, H.R. (2006) Molecular Biology of Amyotrophic Lateral Sclerosis: Insights from Genetics. Nature Reviews Neuroscience, 7, 710-723. http://dx.doi.org/10.1038/nrn1971
[6]	Cassell, G.H. and Cole, B.C. (1981) Mycoplasmas as Agents of Human Diseases. The New England Journal of Medicine, 304, 80-89. http://dx.doi.org/10.1056/NEJM198101083040204
[7]	Nicolson, L.G. (2007) Systemic Intracellular Bacterial Infection (Mycoplasma, Chlamydia, Borrelia Species) in Neurodegenerative (MS, ALS) and Behavioural Disorders (ADS). I Infectious Diseases Newsletter, 1-9.
[8]	Nicolson, L.G. (2008) Chronic Bacterial and Viral Infections in Neurodegenerative and Neurobehavioral Diseases. LabMedicine, 39, 291-299.
[9]	Starakis, I., Panos, G., Koutras, A. and Mazokopakis, E.E. (2011) Pathogens and Chronic or Long-Term Neurologic Disorders. Cardiovascular & Haematological Disorders-Drug Targets, 11, 40-52. http://dx.doi.org/10.2174/187152911795945123
[10]	Sidhu, K.M., Rashidbaigi, A., Testa, D. and Liao, M.J. (1995) Competitor Internal Standards for Quantitative Detection of Mycoplasmal DNA. FEMS Microbiology Letters, 128, 207-212. http://dx.doi.org/10.1111/j.1574-6968.1995.tb07524.x
[11]	Wang, R.Y., Hu, W.S., Dawson, M.S., Shinh, J.W. and Lo, S.C. (1992) Selective Detection of Mycoplasma fermentans by Polymerase Chain Reaction and by Using a Nucleotide Sequence within the Insertion Sequence-Like Element. Journal of Clinical Microbiology, 30, 245-248.
[12]	Bernet, C., Garret, M., De Barbeyrac, B., Bebera, C. and Bonnet, J. (1989) Detection of Mycoplasma pneumoniae by Using the Polymerase Chain Reaction. Journal of Clinical Microbiology, 27, 2492-2496.
[13]	Baseman, B.J. and Tully, G.J. (1997) Mycoplasmas: Sophisticated, Re-Emerging, and Burdened by Their Notoriety. Emerging Infectious Diseases, 3, 21-32.
[14]	Flores, L.J., Ordonez, G. and Pineda, B. (2004) Determinación de infecciones sistémicas por Mycoplasma en pacientes con esclerosis lateral amiotrófica clínicamente definida. Archivos de Neurociencias, 9, 195-201.
[15]	Nicolson, G.L., Nasralla, M., Haier, J. and Pomfret, J. (2002) High Frequency of Systemic Mycoplasmal Infections in Gulf War Veterans and Civilians with Amyotrophic Lateral Sclerosis (ALS). Journal of Clinical Neuroscience, 9, 525-529. http://dx.doi.org/10.1054/jocn.2001.1075
[16]	Chambaud, I., Wróblewski, H. and Blanchard, A. (1999) Interaction between Mycoplasma Lipoprotein and the Host Immune System. Trends in Microbiology, 7, 493-499. http://dx.doi.org/10.1016/S0966-842X(99)01641-8
[17]	Browning, G.F., Marenda, M.S., Noormohammadi, A.H. and Markham, P.F. (2011) The Central Role of Lipoproteins in the Pathogenesis of Mycoplasmoses. Veterinary Microbiology, 153, 44-50. http://dx.doi.org/10.1016/j.vetmic.2011.05.031
[18]	Balish, M.R. and Krause, D.C. (2002) Cythaderence and the Cytoskeleton. In: Razin, S. and Herrmann, R., Eds., Molecular Biology and Pathogenecity of Mycoplasmas, Kluwer Academic Plenum Publisher, New York, 491-518.
[19]	Mcgeer, P.L. and Mcgeer, E.G. (2002) Inflammatory Processes in Amyotrophic Lateral Sclerosis. Muscle & Nerve, 26, 459-470. http://dx.doi.org/10.1002/mus.10191