Mycobacterium marinum, a relatively rapid-growing fish and human pathogen,
has become an important model for the investigation of mycobacterial pathog
enesis. Al. marinum is closely related to the Mycobacterium tuberculosis co
mplex and causes a disease in fish and amphibians with pathology similar to
tuberculosis. We have developed an in vitro model for the study of M. mari
num virulence mechanisms using the carp monocytic cell line CLC (carp leuko
cyte culture). We found that fish monocytes can differentiate between patho
genic and nonpathogenic mycobacterial species. Interestingly, M. marinum en
ters fish monocytes at a 40- to 60-fold-higher rate than Mycobacterium smeg
matis. In addition, M. marinum survives and replicates in fish monocytes wh
ile M. smegmatis is killed. We also found that M. marinum inhibits lysosoma
l fusion in fish monocytes, indicating that these cells may be used to diss
ect the mechanisms of intracellular trafficking in mycobacteria. We conclud
e from these observations that monocytic cells from fish, a natural host fo
r Al. marinum, provide an extremely valuable model for the identification a
nd characterization of mycobacterial virulence determinants in the laborato
ry.