Evolution of Burkholderia pseudomallei in Recurrent Melioidosis

Abstract

Burkholderia pseudomallei, the etiologic agent of human melioidosis, is capable of causing severe acute infection with overwhelming septicemia leading to death. A high rate of recurrent disease occurs in adult patients, most often due to recrudescence of the initial infecting strain. Pathogen persistence and evolution during such relapsing infections are not well understood. Bacterial cells present in the primary inoculum and in late infections may differ greatly, as has been observed in chronic disease, or they may be genetically similar. To test these alternative models, we conducted whole-genome comparisons of clonal primary and relapse B. pseudomallei isolates recovered six months to six years apart from four adult Thai patients. We found differences within each of the four pairs, and some, including a 330 Kb deletion, affected substantial portions of the genome. Many of the changes were associated with increased antibiotic resistance. We also found evidence of positive selection for deleterious mutations in a TetR family transcriptional regulator from a set of 107 additional B. pseudomallei strains. As part of the study, we sequenced to base-pair accuracy the genome of B. pseudomallei strain 1026b, the model used for genetic studies of B. pseudomallei pathogenesis and antibiotic resistance. Our findings provide new insights into pathogen evolution during long-term infections and have important implications for the development of intervention strategies to combat recurrent melioidosis.

The Type VI Secretion System Spike Protein VgrG5 Mediates Membrane Fusion during Intercellular Spread by Pseudomallei Group Burkholderia Species

“…VgrG5 is conserved and functionally interchangeable between Burkholderia pseudomallei and near-neighbor species. Sequence comparisons with VgrG5 encoded by the B. pseudomallei reference genome from strain 1026b (40), the parent of Bp340 (36), indicates high levels of conservation with orthologs in other Pseudomallei group Burkholderia species and strains ( Fig. 2A).…”

Correlates of Immune Protection following Cutaneous Immunization with an Attenuated Burkholderia pseudomallei Vaccine

“…B. pseudomallei strain 1026b (Bp1026b) is a clinical isolate from a patient with septicemic melioidosis in Thailand (45,46). Culture stocks were grown overnight in Luria-Bertani broth (LB) (BD Biosciences, San Jose, CA) at 37°C with shaking.…”

Proteomic Analysis of the Burkholderia pseudomallei Type II Secretome Reveals Hydrolytic Enzymes, Novel Proteins, and the Deubiquitinase TssM

“…In a previous study, we genetically characterized the T2SS of B. pseudomallei 1026b and found that two distinct gsp loci were required for the export of protease, phospholipase C (PLC), and lipase activities (21). The 1026b genome was recently completed (22), and the gspD to -N and gspO loci correspond to BP1026B_I0008 to BP1026B_I0016, BP1026B_I0018, BP1026B_I0019, and BP1026B_I0298, respectively. The specific proteins secreted by T2SS in B.…”