Resistance to phagocyte killing is an important virulence factor in mycobacteria. Dictyostelium has been used to study the interaction between phagocytes and bacteria, given its similarity to the @entity1 macrophage. Here, we investigated the genes responsible for virulence to Dictyostelium by screening 1728 transposon mutants of the @entity15539 NTUH-M6094 strain. A total of 30 mutants that permissive for Dictyostelium growth were identified. These mutants revealed interruptions in 20 distinct loci. Of the 20 loci, six genes (losA, mmar_2318, mmar_2319, wecE, mmar_2323 and mmar_2353) were located in the lipooligosaccharide (LOS) synthesis cluster. LOS are antigenic glycolipids and the core LOS structure from LOS-I to LOS-IV have been reported to exist in @entity15539 . Two-dimensional thin-layer chromatography (2D-TLC) glycolipid profiles revealed that deletion of mmar_2318 or mmar_2319 resulted in the accumulation of @entity942 of LOS-IV. Deletion and complementation of mmar_2318 or mmar_2319 confirmed that these genes both contributed to virulence toward Dictyostelium but not entry and replication inside Dictyostelium. Co-incubation with a @entity19 macrophage cell line J774a.1 or @entity4515 -induced @entity1 monocytic cell line @entity1357 demonstrated that mmar_2318 or mmar_2319 deletion mutant could grow in macrophages, and their initial entry rate was not affected in J774a.1 but significantly increased in @entity1357 . In conclusion, although mmar_2319 has been reported to involve LOS biosynthesis in a previous study, we identified a new gene, mmar_2318 that is also involved in the biosynthesis of LOS. Deletion of mmar_2318 or mmar_2319 both exhibits reduction of virulence toward Dictyostelium and increased entry into @entity1357 cells.

XXXX mmar_2318 and mmar_2319 are Responsible for Lipooligosaccharide Biosynthesis and Virulence Toward Dictyostelium.

@entity1 :: ('9606', 'Species') :: ['mammalian', 'human'] @entity1357 :: ('2736', 'Gene') :: ['THP-1'] @entity19 :: ('10090', 'Species') :: ['murine'] @entity4515 :: ('CHEBI:60755', 'Chemical') :: ['PMA'] @entity15539 :: ('1781', 'Species') :: ['Mycobacterium marinum', 'M. marinum'] @entity942 :: ('MESH:D003677', 'Disease') :: ['LOS-III and deficiency']
@entity15539 :: (1781,Species) :: ['Mycobacterium marinum']
