Influence of iron deprivation on virulence traits of mycobacteria

ABSTRACT Novel strategies to combat the ever increasing burden of drug resistance in Mycobacterium tuberculosis (MTB) causing tuberculosis (TB) remains a global concern. The ability of MTB to sense and adapt to restricted iron conditions in the hostile environment is essential for their survival and confers the basis of their success as dreadful pathogen. The striking and clinically relevant virulence trait of MTB is its ability to form biofilms and adhere to the host cells. The present study elucidated the effect of iron deprivation on biofilm formation and cell adherence of Mycobacterium smegmatis, a non-pathogenic surrogate of MTB. Firstly, we showed that iron deprivation leads to enhanced cell sedimentation rate and altered colony morphology depicting alterations in cell surface envelope properties. We explored that biofilm formation and cell adherence to polystyrene surface as well as human oral epithelial cells were considerably reduced under iron deprivation both in presence of 2,2 BP (iron chelator) and siderophore mutant Δ011-14 strain. We further investigated that the potency of three first line anti-TB drugs (Isoniazid, Ethambutol, Rifampicin) to inhibit both biofilm formation and cell adhesion were enhanced under iron deprivation in contrast to the drugs when tested alone. Taken together, by virtue of the indispensability of iron for functional virulence traits in mycobacteria, iron deprivation strategies could be further exploited against this notorious human pathogen to explore novel drug targets.

Influence of iron deprivation on virulence traits of mycobacteria.

Novel strategies to combat the ever increasing burden of drug resistance in Mycobacterium tuberculosis (MTB) causing tuberculosis (TB) remains a global concern. The ability of MTB to sense and adapt to restricted iron conditions in the hostile environment is essential for their survival and confers the basis of their success as dreadful pathogen. The striking and clinically relevant virulence trait of MTB is its ability to form biofilms and adhere to the host cells. The present study elucidated the effect of iron deprivation on biofilm formation and cell adherence of Mycobacterium smegmatis, a non-pathogenic surrogate of MTB. Firstly, we showed that iron deprivation leads to enhanced cell sedimentation rate and altered colony morphology depicting alterations in cell surface envelope properties. We explored that biofilm formation and cell adherence to polystyrene surface as well as human oral epithelial cells were considerably reduced under iron deprivation both in presence of 2,2 BP (iron chelator) and siderophore mutant Δ011-14 strain. We further investigated that the potency of three first line anti-TB drugs (Isoniazid, Ethambutol, Rifampicin) to inhibit both biofilm formation and cell adhesion were enhanced under iron deprivation in contrast to the drugs when tested alone. Taken together, by virtue of the indispensability of iron for functional virulence traits in mycobacteria, iron deprivation strategies could be further exploited against this notorious human pathogen to explore novel drug targets.

Características clínicas y sociodemográficas de los casos con tuberculosis resistente en el municipio de Armenia, Quindío (Colombia) / Clinical and socio-demographic characteristics of tuberculosis with antimicrobial resistance in Armenia, Quindio (Colombia)

Objetivo: Analizar los factores sociodemográficos y clínicos de los pacientes con diagnóstico de tuberculosis resistente en el municipio de Armenia durante el período 2006-2009. Métodos: Se realizó un estudio descriptivo y retrospectivo con base en la notificación de pacientes con tuberculosis resistentes durante el período de estudio. Los datos fueron tomados de los registros consignados en las fichas de notificación y las tarjetas individuales de tratamiento categoría IV. Resultados: Entre 2006 y 2009, 678 pacientes ingresaron en el programa de control de la tuberculosis. De ellos, 14 casos (2,0%) fueron resistentes al menos a un medicamento, y entre estos, 7 (50%) fueron multirresistentes. El 21% estuvo asociado a infección por virus de la inmunodeficiencia humana. La tasa de fallecimientos en pacientes con tuberculosis con farmacorresistencia múltiple fue del 71%. Se encontró amplificación de la resistencia en 2 casos, quienes presentaron deterioro en el estado de salud y deceso. Conclusión: La situación en Armenia de resistencia a antituberculosos es de proporción similar a la del resto del país. Se encontraron factores de riesgo conocidos en los casos de resistencia (coinfección con virus de la inmunodeficiencia humana, farmacodependencia, abandono social) en la mayoría de casos, pero también de resistencia primaria y sin factores de riesgo con farmacorresistencia múltiple y una alta mortalidad, lo que llama la atención para mejorar la vigilancia y el control de los casos en tratamiento en la ciudad.

Objective: To analyze the socio-demographic and clinical diagnosis of patients with resistant tuberculosis in the municipality of Armenia in the period 2006-2009. Methods: We performed a retrospective descriptive study based on the notification of patients with resistant tuberculosis during the study period, data were taken from registrations under notification forms and individual treatment cards category IV. Results: 678 patients were admitted to the program of tuberculosis control between 2006 and 2009, 14 cases (2,0%) were resistant to at least one drug and from these cases 7 were multidrug resistant (MDR). In 21% of cases there was co-infection with HIV. The death rate in patients with MDR-TB was 71%. Amplification in resistance was observed in two cases which lead to further deterioration in the health status and death. Conclusion: Armenia has levels of resistance to anti tuberculosis drugs similar to the reported in the rest of Colombia. We found factors already know to be associated with resistance (drug addiction, social abandon, HIV co infection) but there were also cases without these factors and with primary MDR and high mortality, therefore is urgent to improve the public health measures for cases under treatment in this city.