Abstract
ABSTRACTIn many bacteria, the FtsH protease and its modulators, HflK and HflC, form a large protein complex that contributes to both membrane protein quality control and regulation of the cellular response to environmental stress. Both activities are crucial to the Lyme disease pathogen Borrelia burgdorferi, which depends on membrane functions, such as motility, protein transport, and cell signaling, to respond to rapid changes in its environment. Using an inducible system, we demonstrate that FtsH production is essential for both mouse and tick infectivity and for in vitro growth of B. burgdorferi. FtsH depletion in B. burgdorferi cells resulted in membrane deformation and cell death. Overproduction of the protease did not have any detectable adverse effects on B. burgdorferi growth in vitro, suggesting that excess FtsH does not proteolytically overwhelm its substrates. In contrast, we did not observe any phenotype for cells lacking the protease modulators HflK and HflC (ΔHflK/C), although we examined morphology, growth rate, growth under stress conditions, and the complete mouse-tick infectious cycle. Our results demonstrate that FtsH provides an essential function in the life cycle of the obligate pathogen B. burgdorferi but that HflK and HflC do not detectably affect FtsH function.
Highlights
In many bacteria, the FtsH protease and its modulators, HflK and HflC, form a large protein complex that contributes to both membrane protein quality control and regulation of the cellular response to environmental stress
B. burgdorferi BB0789, BB0203, and BB0204 are annotated as homologs of E. coli FtsH, HflK, and HflC in the NCBI database [16]
Nutrients, cell density, pH, and temperature all shift between hosts, and many of these cues result in production of different proteins [28,29,30,31,32]
Summary
The FtsH protease and its modulators, HflK and HflC, form a large protein complex that contributes to both membrane protein quality control and regulation of the cellular response to environmental stress Both activities are crucial to the Lyme disease pathogen Borrelia burgdorferi, which depends on membrane functions, such as motility, protein transport, and cell signaling, to respond to rapid changes in its environment. Several reports indicate that HflK/C acts as a negative regulator of membrane substrates, selectively allowing specific membrane proteins access to the active site chamber of FtsH [11, 12, 14] These results are complex and not completely understood, evidence suggests that entry of cytoplasmic substrates into the FtsH protease may occur through a separate process [14]. Unlike FtsH, HflK and HflC are not essential to E. coli and can be inactivated, with the main observable phenotype being a high frequency of lysogenization by phage [12]
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