Borrelia burgdorferi σ54 is required for mammalian infection and vector transmission but not for tick colonization

Previous studies have shown that a sigma(54)-sigma(S) cascade regulates the expression of a few key lipoproteins in Borrelia burgdorferi, the agent of Lyme disease. Here, we demonstrate that these sigma factors, both together and independently, regulate a much more extensive number of genes and cellular processes. Microarray analyses of sigma(54) and sigma(s) mutant strains identified 305 genes regulated by sigma(54) and 145 regulated by sigma(s), whereas the sigma(54)-sigma(s) regulatory cascade appears to control 48 genes in B. burgdorferi. In silico analyses revealed that nearly 80% of genes with altered expression in the sigma(54) mutant were linked to potential sigma(54)-dependent promoters. Many sigma(54)-regulated genes are expressed in vivo, and through genetic complementation of the mutant, we demonstrated that sigma(54) was required by B. burgdorferi to infect mammals. Surprisingly, sigma(54) mutants were able to infect Ixodes scapularis ticks and be maintained for at least 24 wk after infection, suggesting the sigma(54)-sigma(s) regulatory network was not involved in long-term survival in ticks. However, sigma(54) mutants did not enter the salivary glands during tick feeding, indicating that sigma(54)-regulated genes were involved in the transmission process.