Experimental selection of long-term intracellular mycobacteria

VÁZQUEZ CL; LERNER TR; KASMAPOUR B; PEI G; GRONOW A; BIANCO MV; BLANCO FC; BLECK CK; GEFFERS R; BIGI F; ABRAHAM WR; GUTIERREZ M

CELLULAR MICROBIOLOGY (PRINT)

WILEY-BLACKWELL PUBLISHING, INC

Año: 2014 p. 1 - 10

1462-5814

Abstract Some intracellular bacteria are known to cause long-term infections that last decades without compromising the viability of the host. Although of critical importance, the adaptations that intracellular bacteria undergo during this long process of residence in a host cell environment remain obscure. Here, we report a novel experimental approach to study the adaptations of mycobacteria imposed by a long-term intracellular lifestyle. Selected Mycobacterium bovis BCG through continuous culture in macrophages underwent an adaptation process leading to impaired phenolic glycolipids (PGL) synthesis, improved usage of glucose as a carbon source and accumulation of neutral lipids. These changes correlated with increased survival of mycobacteria in macrophages and mice during re-infection and also with the specific expression of stress- and survival-related genes. Our findings identify bacterial traits implicated in the establishment of long-term cellular infections and represent a tool for understanding the physiological states and the environment that bacteria face living in fluctuating intracellular environments.