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The susceptibility of mobile and cystic forms of Borrelia burgdorferi to tinidazole (TZ) was examined. The minimal bactericidal concentration (MBC) of TZ against the mobile spirochetes was >128 µg/ml at 37°C in micro-oxic atmosphere when incubated for 14 days. TZ significantly reduced the conversion of mobile spirochetes to cystic forms during incubation. The MBC for older (10-months-old) cysts at 37°C in a micro-oxic atmosphere was >0.5 µg/ml, but >0.125 µg/ml for young (1-day-old) cysts. Acridine orange staining, dark-field microscopy and transmission electron microscopy revealed that, when the concentration of TZ was ≥ MBC, the contents of the cysts were partly degraded, core structures did not develop inside the young cysts, and the amount of RNA in these cysts decreased significantly. When cysts were exposed to TZ, both the spirochetal structures and core structures inside the cysts dissolved, and the production of blebs was significantly reduced. These observations may be valuable in the treatment of resistant infections caused by B. burgdorferi, and suggest that a combination of TZ and a macrolide antibiotic could eradicate both cystic and mobile forms of B. burgdorferi. Este estudio examina la susceptibilidad al tinidazol (TZ) de las formas móviles y císticas de Borrelia burgdorferi. La concentración bactericida mínima (CBM) de TZ para las espiroquetas móviles era >128 mg/ml a 37°C en atmosfera microóxica e incubación durante 14 días. El TZ redujo significativamente la conversión de espiroquetas móviles a la forma cística durante la incubación. La CBM para los cistos viejos (de 10 meses) a 37°C y en atmosfera microóxica era >0.5 mg/ml, mientras para los cistos jóvenes (de un día) era >0.125 mg/ml. La tinción con naranja de acridina, la microscopia de campo oscuro, y la microscopia electrónica de transmisión mostraron que cuando la concentración de TZ era ≥MBC el contenido de los cistos se degradaba parcialmente, no se desarrollaban las estructuras nucleares en el interior de los cistos jóvenes, y la cantidad de RNA en dichos cistos disminuía significativamente. Cuando los cistos se exponían a TZ, las estructuras espiroquetales y nucleares de su interior se disolvían, y la producción de vesículas se reducía significativamente. Estas observaciones pueden ser importantes en el tratamiento de infecciones resistentes causadas por B. burgdorferi, y sugieren que la combinación de TZ con un antibiótico macrólido podría erradicar tanto las formas císticas de B. burgdorferi como las móviles. Este estudo examina a susceptibilidade das formas móveis e císticas de Borrelia burgdorferi ao tinidazol (TZ). A mínima concentração bactericida (MCB) de TZ para as espiroquetas móveis foi >128 mg/ml a 37°C em atmosfera microóxica e incubação durante 14 dias. O TZ reduziu significantemente a conversão das espiroquetas móveis à forma cística, durante a incubação. A CBM para os cistos velhos (de 10 meses) a 37°C e em atmosfera microóxica era >0,5 mg/ml, enquanto que para os cistos jovens (de um dia) era >0,125 mg/ml. A coloração com acridina laranja, a microscopia de campo escuro e a microscopia eletrônica de transmissão mostraram que quando a concentração de TZ era ≥CBM o conteúdo dos cistos se degradava parcialmente, não se desenvolviam as estruturas nucleares no interior dos cistos jovens e a sua quantidade de RNA diminuía significantemente. Quando os cistos se expunham a TZ, as estruturas espiroquetais e as nucleares de seu interior se dissolviam e a produção de vesículas se reduzia significantemente. Estas observações podem ser importantes no tratamento de infecções resistentes causadas por B. burgdorferi e sugerem que a combinação de TZ com um antibiótico macrólido poderia erradicar tanto as formas císticas de B. burgdorferi como as móveis.

The susceptibility of mobile and cystic forms of Borrelia burgdorferi to tinidazole (TZ) was examined. The minimal bactericidal concentration (MBC) of TZ against the mobile spirochetes was >128 µg/ml at 37°C in micro-oxic atmosphere when incubated for 14 days. TZ significantly reduced the conversion of mobile spirochetes to cystic forms during incubation. The MBC for older (10-months-old) cysts at 37°C in a micro-oxic atmosphere was >0.5 µg/ml, but >0.125 µg/ml for young (1-day-old) cysts. Acridine orange staining, dark-field microscopy and transmission electron microscopy revealed that, when the concentration of TZ was ≥ MBC, the contents of the cysts were partly degraded, core structures did not develop inside the young cysts, and the amount of RNA in these cysts decreased significantly. When cysts were exposed to TZ, both the spirochetal structures and core structures inside the cysts dissolved, and the production of blebs was significantly reduced. These observations may be valuable in the treatment of resistant infections caused by B. burgdorferi, and suggest that a combination of TZ and a macrolide antibiotic could eradicate both cystic and mobile forms of B. burgdorferi.