Phenotypic consequences of red-white colony type variation in Mycobacterium avium

Mycobacterium avium undergoes reversible morphotypic switching between the virulent transparent colony type and the less virulent opaque colony type. A new morphotypic switch in M. avium, termed red-white, that becomes visibl e when opaque colonies of clinical isolates are grown on agar media contain ing Congo red, was recently described. White opaque (WO) variants were foun d to be more resistant to multiple antibiotics than were red opaque (RO) va riants. The present paper reports that transparent derivatives of RO and WO clones retain the differential Congo red binding properties of their opaqu e parents, indicating that the opaque-transparent switch operates independe ntly of the red-white switch. White transparent variants were more resistan t to clarithromycin and rifampin in vitro, and better able to survive withi n human macrophages, than their red transparent counterparts. Neither red n or white variants were markedly favoured during growth in vitro; however, r ed variants were better able to spread on soft agar (sliding motility), a p otential selective advantage under some environmental circumstances. White- to-red switching was frequently observed in vitro and was accompanied by de creased antibiotic resistance and increased motility. Red-to-white switchin g has yet to be observed in vitro, indicating that the red morphotype is ve ry stable. Significantly, some widely studied laboratory reference strains of M. avium, including strain 2151 and the genome sequence strain 104 are s table red clones. These strains are intrinsically antibiotic resistant and virulent in animal models, but they may not express genes encoding the elev ated levels of antibiotic resistance and intracellular survival observed in white variants.