Mechanisms of latency in Mycobacterium tuberculosis

Parrish, Nikki; Dick, James D.; Bishai, William R.

doi:10.1016/s0966-842x(98)01216-5

Cited by 410 publications

(319 citation statements)

References 32 publications

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“…As the immune system begins to fail, latent infection can be reactivated, leading to the development of active TB, frequently several decades after initial infection. Reactivation can be induced by various factors, all of which compromise the immune system's efficacy, such as HIV co-infection, malnutrition, aging, drug use, cancer, diabetes, chronic renal insufficiency and immunosuppressive drug therapy (Parrish et al 1998).…”

Section: Tuberculosis Latency and Reactivationmentioning

confidence: 99%

The resumption of consumption: a review on tuberculosis

Ruffino-Netto

Basso

Santos

2006

Mem. Inst. Oswaldo Cruz

166

135

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Section: Tuberculosis Latency and Reactivationmentioning

confidence: 99%

The resumption of consumption: a review on tuberculosis

Ruffino-Netto

Basso

Santos

2006

Mem. Inst. Oswaldo Cruz

166

135

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“…The latent bacilli can persist in a somewhat ill-defined physiological state in pulmonary and extrapulmonary lesions for years after infection (30). These bacilli are opportunistic and can reactivate themselves when the host is immunocompromised.…”

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confidence: 99%

High Intracellular Level of Guanosine Tetraphosphate in Mycobacterium smegmatis Changes the Morphology of the Bacterium

2000

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Almost one-third of the world population today harbors the tubercle bacillus asymptomatically. It is postulated that the morphology and staining pattern of the long-term persistors are different from those of actively growing culture. Interestingly, it has been found that the morphology and staining pattern of the starved in vitro population of mycobacteria is similar to the persistors obtained from the lung lesions. In order to delineate the biochemical characteristics of starved mycobacteria, Mycobacteria smegmatis was grown in 0.2% glucose as a sole carbon source along with an enriched culture in 2% glucose. Accumulation of the stringent factor guanosine tetraphosphate (ppGpp) with a concomitant change in morphology was observed for M. smegmatis under carbon-deprived conditions. In addition, M. smegmatis assumed a coccoid morphology when ppGpp was ectopically produced by overexpressing Escherichia coli relA, even in an enriched medium. The Mycobacterium tuberculosis relA and spoT homologue, when induced in M. smegmatis, also resulted in the overproduction of ppGpp with a change in the bacterium's growth characteristics.Mycobacteria have emerged as a major threat to humankind, for as many as one-third of the world's population (1.7 billion) harbors the tubercle bacillus asymptomatically (18). The latent bacilli can persist in a somewhat ill-defined physiological state in pulmonary and extrapulmonary lesions for years after infection (30). These bacilli are opportunistic and can reactivate themselves when the host is immunocompromised. To add to the misery, persistors require prolonged therapy, and Mycobacterium bovis BCG vaccination has little effect in blocking reactivation of the bacteria. Hence, for improved control of tuberculosis, it is imperative to develop effective drugs to cease the propagation and persistence of these latent bacilli. This will be greatly facilitated by a better understanding of the physiological state of these latent bacteria. Although several in vitro models suggest low extracellular concentrations of oxygen to be an important cause for mycobacterial dormancy (8,10,42), the effect of this state on cellular metabolism is not clear.It has been shown that the morphology and staining pattern of an in vitro culture of mycobacteria differ from those of persistors which are obtained from the lung lesion and are chromophobic to the conventional acid-fast staining (25, 26). The former is an acid-fast and long rod-shaped bacillus, as opposed to the latter, which is non-acid fast and granular. However, these persistors can be stained after oxidizing the cell surface with periodic acid. In yet another important observation, it has been shown that the morphology and staining pattern of such persistors can be obtained in vitro by starving the Mycobacterium tuberculosis, Mycobacterium kansasii, or Mycobacterium pheli cultures on agar plates without any nutrients (26). This key observation suggests that the natural persistors may be physiologically similar to bacteria in nutritionally starved cultu...

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“…Se estima que individuos con infección latente y sin factores de riesgo asociados tienen 2 a 23% de riesgo de desarrollar en toda su vida una reactivación a largo plazo de la TB. Por el contrario, individuos co-infectados con HIV o inmuno deprimidos, por otra causa, tienen un riesgo de 5 a10% anual de reactivación 12 .…”

Section: Mycobacterium Tuberculosisunclassified

Factores de virulencia de Mycobacterium tuberculosis

Maulén¹

2011

Rev. méd. Chile

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Situación mundial de la tuberculosisM ycobacterium tuberculosis (Mtb), agente etiológico de la tuberculosis (TB) humana, causa anualmente alrededor de tres millones de muertes e infecta de manera latente entre uno y dos billones de personas. El resurgimiento mundial de la TB se atribuye al aumento de la migración internacional, fallas en los sistemas de salud público, inefi cacia de la vacuna BCG, la pobreza de ciertos países de África, Asia y Améri-ca Latina, la baja sensibilidad de los métodos de diagnóstico, pero por sobre todo a la pandemia VIH/SIDA 1,2 . Se estima que 4% de los casos corresponden a Mtb resistentes a más de una droga antituberculosa (MDR-TB), condición difícil de tratar, costosa y no siempre curable. En el caso de cepas ultra resistentes (MDXR-TB) prácticamente no hay opción de tratamiento. Más aun, las drogas disponibles son inefi caces para el tratamiento de individuos infectados de manera latente [3][4][5][6] . La Organización Mundial de la Salud reporta que la carga mundial de TB está disminuyendo. Se espera que tres regiones alcancen en el 2015 las metas mundiales. No obstante, se estima que 37% de los casos incidentes de TB no está siendo tratado en programa DOTS (Directly observed therapy short-course), que 96% de los casos MDR-TB no está siendo diagnosticados y tratados, que la mayoría de los casos TB-VIH-positivos desconocen que lo son, y que la mayoría de los casos TB-VIH-positivos, que lo saben, no tiene acceso a farmacoterapia 2 . En Chile, la endemia ha evolucionado favorablemente con una tendencia declinante de la morbilidad, lo que permite pensar en un importante progreso hacia la eliminación de la TB. Sin embargo, la extrema variabilidad entre regiones es una de las características epidemiológicas relevantes de la situación actual y de los problemas que se deberán superar para avanzar hacia la fase de "eliminación avanzada" 7 .Las actuales medidas mundiales de control de la TB no han sido sufi cientes para interrumpir la

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Mechanisms of latency in Mycobacterium tuberculosis

Cited by 410 publications

References 32 publications

The resumption of consumption: a review on tuberculosis

The resumption of consumption: a review on tuberculosis

High Intracellular Level of Guanosine Tetraphosphate in Mycobacterium smegmatis Changes the Morphology of the Bacterium

Factores de virulencia de Mycobacterium tuberculosis

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