Proteome Analysis of Borrelia burgdorferi Response to Environmental Change

Abstract

We examined global changes in protein expression in the B31 strain of Borrelia burgdorferi, in response to two environmental cues (pH and temperature) chosen for their reported similarity to those encountered at different stages of the organism's life cycle. Multidimensional nano-liquid chromatographic separations coupled with tandem mass spectrometry were used to examine the array of proteins (i.e., the proteome) of B. burgdorferi for different pH and temperature culture conditions. Changes in pH and temperature elicited in vitro adaptations of this spirochete known to cause Lyme disease and led to alterations in protein expression that are associated with increased microbial pathogenesis. We identified 1,031 proteins that represent 59% of the annotated genome of B. burgdorferi and elucidated a core proteome of 414 proteins that were present in all environmental conditions investigated. Observed changes in protein abundances indicated varied replicon usage, as well as proteome functional distributions between the in vitro cell culture conditions. Surprisingly, the pH and temperature conditions that mimicked B. burgdorferi residing in the gut of a fed tick showed a marked reduction in protein diversity. Additionally, the results provide us with leading candidates for exploring how B. burgdorferi adapts to and is able to survive in a wide variety of environmental conditions and lay a foundation for planned in situ studies of B. burgdorferi isolated from the tick midgut and infected animals.

Altered Murine Tissue Colonization by Borrelia burgdorferi following Targeted Deletion of Linear Plasmid 17-Carried Genes

“…Using targeted plasmid deletion, the majority of this plasmid has been shown not to be required for viability in the noninfectious strain B31-A; however, a role for lp17 during infectivity or persistence has not been evaluated in an infectious background. Recently, many of the genes on lp17 have been shown to undergo changes in expression under culture conditions that mimic either the tick vector or the mammalian host (1,9,38,42,58). Further studies using mutant strains lacking alternative sigma factors involved in regulating the expression of host-specific genes showed similar alterations in the expression levels of lp17-borne genes (7,11,43,44,49).…”

Outer Membrane Proteins BB0405 and BB0406 Are Immunogenic, but Only BB0405 Is Required for Borrelia burgdorferi Infection

“…Previous studies also revealed that bb0405, but not bb0406, is upregulated by temperature and by conditions that mimic the transmission of B. burgdorferi from feeding ticks to the mammalian host (52). Consistent with the notion that the BB0405 and BB0406 proteins are differentially expressed during infection, a recent Borrelia burgdorferi global proteome analysis showed that BB0405 and BB0406 are variably expressed in different environments (53). Data from those previous studies, combined with the observation that BB0406 antibodies develop much later during infection than do BB0405 antibodies, strongly suggest that BB0405 and BB0406 are cotranscribed but not coexpressed during infection.…”

Enhanced Adhesion and OspC Protein Synthesis of the Lyme Disease Spirochete Borrelia Burgdorferi Cultivated in a Host-Derived Tissue Co-Culture System

“…Information acquired from different culture conditions indicated that systemic adaptations of the proteome occur as B. burgdorferi moves from one environment to another. A significant increase in the abundance of many outer surface exposed proteins (OspC, LA7, P66, P83 and P35 antigens) was observed in this study (10). The aim of our study was to investigate the influence of host tissues on the infection process, especially adherence of pathogenic or non-pathogenic B. burgdorferi, with emphasis on the synthesis of OspA and OspC.…”