Genomic rearrangements in the flagellin genes of Proteus mirabilis

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Abstract
Molecular analyses have revealed that Proteus mirabilis possesses two genes, flaA and flaB, that are homologous to each other and to flagellin genes of many other species. Both swimmer and swarmer cells transcribe flaA, but not flaB. FlaA− mutants are non‐motile and do not differentiate showing the essential role of flaA in swarmer cell differentiation and behaviour. At a low frequency, motile, differentiation‐proficient revertants have been found in FlaA− populations. These revertants produce an antigenically and biochemically distinct flagellin protein. The revertant flagellin is the result of a genetic fusion between highly homologous regions of flaA and flaB that places the active flaA promoter and the 5′ coding region of flaA adjacent to previously silent regions of flaB generating a hybrid flagellin protein. Analysis of the flaA–flaB region of two such revertants reveals that a portion of this locus has undergone a rearrangement and deletion event that is unique to each revertant. Using a polymerase chain reaction (PCR) to amplify the flaA–flaB locus from wild‐type swimmer cells, swarmer cells and cells obtained after urinary tract infection, we uncover at least six general classes of rearrangements between flaA and flaB. Each class of rearrangement occurs within one of nine domains of homology between flaA and flaB. Rearrangement of flaA and flaB results in a hybrid flagellin protein of nearly identical size and biochemical properties, suggesting a concerted mechanism may be involved in this process. The data also reveal that the frequency and distribution of flaAB rearrangements is predicated on environmental conditions. Thus, rearrangement between flaA and flaB may be a significant virulence component of P. mirabilis in urinary tract infections.