Borrelia burgdorferi sigma super(54) is required for mammalian infection and vector transmission but not for tick colonization

Previous studies have shown that a sigma super(54)- sigma super(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 super(54) and sigma super(S) mutant strains identified 305 genes regulated by sigma super(54) and 145 regulated by sigma super(S) sub(,) whereas the sigma super(54)- sigma super(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 super(54) mutant were linked to potential sigma super(54)-dependent promoters. Many sigma super(54)-regulated genes are expressed in vivo, and through genetic complementation of the mutant, we demonstrated that sigma super(54) was required by B. burgdorferi to infect mammals. Surprisingly, sigma super(54) mutants were able to infect Ixodes scapularis ticks and be maintained for at least 24 wk after infection, suggesting the sigma super(54)- sigma super(S) regulatory network was not involved in long-term survival in ticks. However, sigma super(54) mutants did not enter the salivary glands during tick feeding, indicating that sigma super(54)-regulated genes were involved in the transmission process.