Highly resistant Burkholderia pseudomallei small colony variants isolated in vitro and in experimental melioidosis

Burkholderia pseudomallei is the causative agent of melioidosis, a disease in which treatment failures and relapses are common. This study reports on slow growing B. pseudomallei 'small colony variants' (SCVs), isolated eithe r in vitro after exposure to ceftazidime, ciprofloxacin or gentamicin or fr om the spleen and liver in a mouse model of melioidosis after treatment wit h ceftazidime. Interestingly, SCVs isolated by either method or antimicrobi al agent showed a significant increase in the minimal inhibitory concentrat ions of various unrelated classes of antimicrobial agents. B. pseudomallei SCVs did not differ from their parental strains in standard biochemical pro files, nor by pulsed field gel electrophoresis or electron microscopy. Alth ough the SCV phenotype was stable throughout numerous passages on antibioti c-free solid media, revertants with the parental colony morphology and, mos t importantly, with the parental susceptibility pattern occurred. These rev ertants led to rapid overgrowth of SCVs in liquid media without added antib iotics. Future studies will have to determine the clinical relevance of B. pseudomallei SCVs especially in treatment failure and relapse of infection.