Burkholderia pseudomallei is a Gram-negative bacterium that causes melioidosis, which can be fatal in humans. Melioidosis is prevalent in the tropical regions of Southeast Asia and Northern Australia. Ecological data have shown that this bacterium can survive as a free-living organism in environmental niches, such as soil and water, as well as a parasite living in host organisms, such as ameba, plants, fungi, and animals. This review provides an overview of the survival and adaptation of B. pseudomallei to stressful conditions induced by hostile environmental factors, such as salinity, oxidation, and iron levels. The adaptation of B. pseudomallei in host cells is also reviewed. The adaptive survival mechanisms of this pathogen mainly involve modulation of gene and protein expression, which could cause alterations in the bacteria's cell membrane, metabolism, and virulence. Understanding the adaptations of this organism to environmental factors provides important insights into the survival and pathogenesis of B. pseudomallei, which may lead to the development of novel strategies for the control, prevention, and treatment of melioidosis in the future.

Serial passage is a problem among many bacterial species, especially those where strains have been stored (banked) for several decades. Prior to banking with an organization such as ATCC, many bacterial strains were passaged for many years, so the characteristics of each strain may be extremely different. This is in addition to any differences in the original host environment. For Burkholderia pseudomallei, the number of serial passages should be carefully defined for each experiment because it undergoes adaptation during the course of serial passages. In the present study, we found that passaged B. pseudomallei fresh clinical isolates and reference strain in Luria-Bertani broth exhibited increased plaque formation, invasion, intracellular replication, Galleria mellonella killing abilities, and cytokine production of host cells. These bacteria also modulated proteomic profiles during in vitro passage. We presume that the modulation of protein expression during in vitro passage caused changes in virulence and immunogenicity phenotypes. Therefore, we emphasize the need for caution regarding the use of data from passaged B. pseudomallei. These findings of phenotypic adaptation during in vitro serial passage can help researchers working on B. pseudomallei and on other species to better understand disparate findings among strains that have been reported for many years. Burkholderia pseudomallei is a Gram-negative facultative intracellular bacterium and the causative agent of melioidosis, a life threatening disease in humans and animals 1-3. Melioidosis is an important health problem due to poor understanding of the disease process, frequency of misdiagnosis, and lack of effective vaccination 4,5. Therefore, B. pseudomallei clinical and laboratory isolates have been extensively used to investigate pathogenic mechanisms of bacteria contributing to the disease. Serial passages are routinely performed to maintain an active culture or expand the bacterial number. Serial passages may influence bacterial adaptation through genotypic and phenotypic alterations. In a closely related organism, Burkholderia mallei, genome alterations (e.g. gene insertions, deletions, and repetitive sequences) were observed during in vitro passage 6. However, minimal information has been published regarding B. pseudomallei adaptation during serial passage. U' Ren et al. examined genomic mutations in B. pseudomallei that was serially passaged in vitro for 10 days; they found that tandem repeat genome mutations occurred, and suggested that these tandem repeat regions may contribute to generation and maintenance of adaptive genomic variation in B. pseudomallei 7. It was suggested that these tandem repeat regions may play role in generating and maintaining adaptive genomic variation in B. pseudomallei 7. It is likely that B. pseudomallei has an unstable genome 7 , which could be beneficial for bacterial adaptation and evolution. In addition, Price et al. characterized tandem repeat genome mutations in B. pseudomallei isolates from multiple body sites...