Mycobacterium leprae's Infective Capacity Is Associated with Activation of Genes Involved in PGL-I Biosynthesis in a Schwann Cells Infection Model.

Peripheral nerves and Schwann cells (SCs) are privileged and protected sites for initial colonization, survival, and spread of leprosy bacillus. Mycobacterium leprae strains that survive multidrug therapy show a metabolic inactivation that subsequently induces the recurrence of typical clinical manifestations of leprosy. Furthermore, the role of the cell wall phenolic glycolipid I (PGL-I) in the M. leprae internalization in SCs and the pathogenicity of M. leprae have been extensively known. This study assessed the infectivity in SCs of recurrent and non-recurrent M. leprae and their possible correlation with the genes involved in the PGL-I biosynthesis. The initial infectivity of non-recurrent strains in SCs was greater (27%) than a recurrent strain (6.5%). In addition, as the trials progressed, the infectivity of the recurrent and non-recurrent strains increased 2.5- and 2.0-fold, respectively; however, the maximum infectivity was displayed by non-recurrent strains at 12 days post-infection. On the other hand, qRT-PCR experiments showed that the transcription of key genes involved in PGL-I biosynthesis in non-recurrent strains was higher and faster (Day 3) than observed in the recurrent strain (Day 7). Thus, the results indicate that the capacity of PGL-I production is diminished in the recurrent strain, possibly affecting the infective capacity of these strains previously subjected to multidrug therapy. The present work opens the need to address more extensive and in-depth studies of the analysis of markers in the clinical isolates that indicate a possible future recurrence.

Detección molecular de sífilis gestacional y congénita / Molecular detection of gestational and congenital syphilis

Objetivo: estandarizar una qPCR para la determinación de T. pallidum en muestras de suero de pacientes con sífilis gestacional y congénita. Materiales y métodos: se optimizó una qPCR con sonda para la amplificación del gen TpN47 en muestras de suero, se evaluó la sensibilidad, especificidad y eficiencia analítica de la técnica. Se comparó con pruebas serológicas (VDRL y TPPA) y se calculó índice de concordancia Kappa. Resultados: la qPCR mostró un límite de detección de 0.113 femtogramos, especificidad analítica del 100% y fidelidad de 104%. Se evidenció correlación optima en la prueba, sugerida por un r2 de 0.99 y un valor p <0,0001 de la qPCR. Se observó acuerdo entre las pruebas serológicas y moleculares. Conclusiones: se desarrolló una herramienta molecular prometedora con buena sensibilidad, óptima especificidad analítica y gran potencial diagnóstico para la detección y hallazgo de T. pallidum subsp. pallidum, a través de la amplificación del gen TpN47 en muestras clínicas de pacientes con diagnóstico presuntivo de sífilis gestacional y congénita.

Objective: to evaluate a qPCR to detect T.pallidum in serum samples from patients with gestational and congenital syphilis. Methodology: qPCR with probe was optimized for the amplification of the TpN47 gene in serum samples, the sensitivity, specificity and analytical efficiency of the technique were evaluated. It was compared with the serological tests (VDRL and TPPA) and the Kappa concordance index was calculated. Results: the qPCR showed a detection limit of 0.113 femtograms, an analytical specificity of 100% and an accuracy of 104%. Optimal correlation was evidenced in the test, suggested by an r2 of 0.99 and a p value <0.0001 of the qPCR. An agreement was observed between serological and molecular tests. Conclusion: a promising molecular tool was developed with good sensitivity, excellent analytical specificity and great diagnostic potential for the detection and finding of T. pallidum subsp. pallidum, through the amplification of the TpN47 gene in serum from patients with gestational and congenital syphilis.

Mycobacterium leprae's evolution and environmental adaptation.

Leprosy is an ancient disease caused by the acid-fast bacillus Mycobacterium leprae, also known as Hansen's bacillus. M. leprae is an obligate intracellular microorganism with a marked Schwann cell tropism and is the only human pathogen capable of invading the superficial peripheral nerves. The transmission mechanism of M. leprae is not fully understood; however, the nasal mucosa is accepted as main route of M. leprae entry to the human host. The complete sequencing and the comparative genome analysis show that M. leprae underwent a genome reductive evolution process, as result of lifestyle change and adaptation to different environments; some of lost genes are homologous to those of host cells. Thus, M. leprae reduced its genome size to 3.3 Mbp, contributing to obtain the lowest GC content (approximately 58%) among mycobacteria. The M. leprae genome contains 1614 open reading frames coding for functional proteins, and 1310 pseudogenes corresponding to 41% of the genome, approximately. Comparative analyses to different microorganisms showed that M. leprae possesses the highest content of pseudogenes among pathogenic and non-pathogenic bacteria and archaea. The pathogen adaptation into host cells, as the Schwann cells, brought about the reduction of the genome and induced multiple gene inactivation. The present review highlights the characteristics of genome's reductive evolution that M. leprae experiences in the genetic aspects compared with other pathogens. The possible mechanisms of pseudogenes formation are discussed.

La Lepra: una enfermedad vigente / Leprosy: an ongoing disease

El libro resalta que la lepra continúa siendo una enfermedad presente en Colombia y que aún constituye un problema de salud pública importante por los costos sociales, económicos y de sufrimiento humano que conlleva. Sabiendo que la literatura sobre el tema es escasa en nuestro medio, este libro surge como una herramienta de consulta creada para médicos y otros profesionales de salud, con la certeza de que es preciso mejorar la oportunidad del diagnóstico. Siendo fundamental que, durante su proceso formativo, todos los profesionales de la salud adquieran conocimientos sobre dicha enfermedad, que cada día se hace más visible por sus secuelas y diagnóstico tardío.

The book highlights the fact that leprosy continues to be a disease present in Colombia and that it is still a major public health problem due to the social, economic and human suffering costs it entails. Knowing that the literature on the subject is scarce in our country, this book is intended as a reference tool for doctors and other health professionals, in the knowledge that it is necessary to improve the timeliness of diagnosis. It is essential that, during their training process, all health professionals acquire knowledge about this disease, which is becoming more and more visible every day due to its sequelae and late diagnosis.