A nonswarming mutant of Proteus mirabilis lacks the Lrp global transcriptional regulator

Abstract

Proteus swarming is the rapid cyclical population migration across surfaces by elongated cells that hyperexpress flagellar and virulence genes. The mini-Tn5 transposon mutant mns2 was isolated as a tight nonswarming mutant that did not elongate or upregulate flagellar and hemolysin genes. Individual cell motility was retained but was reduced. The transposon had inserted in the gene encoding the global transcriptional regulator Lrp (leucine-responsive regulatory protein), expression of which was upregulated in differentiating swarm cells. Swarming was restored to the lrp mutant by artificial overexpression of the flhDC flagellar regulatory master operon. Lrp may be a key component in generating or relaying signals that are required for flagellation and swarming, possibly acting through the flhDC operon.Swarming migration in Proteus mirabilis involves the coordinate differentiation of short motile vegetative cells with a few peritrichous flagella into multinucleate, aseptate swarm cells of up to 40-fold vegetative cell length and with a more than 50-fold greater density of surface flagella. Swarm cells migrate rapidly away from the colony as multicellular rafts until they pause (consolidate) and undergo some dedifferentiation. Cycles of differentiation and consolidation follow, generating a macroscopic pattern of concentric rings or terraces (1). Swarming is suggested to play a role in urinary tract colonization by Proteus mirabilis (4, 6), and hyperexpression of fliC and other flagellar genes is paralleled by the coordinate upregulation of virulence genes, e.g., hpmBA encoding hemolysin toxin (3).In contrast to differentiation among other bacteria, swarming appears not to be a starvation response but is rather stimulated by high growth rates (29) and is probably influenced by multiple environmental signals, such as cell density and the presence of amino acids and possibly peptides (5, 23, 38). Characterization of swarming-defective Proteus transposon mutants has indicated the involvement of a substantial number of genes involved in differentiation and subsequent population migration (2,9,10,23,(25)(26)(27). Both hyperflagellation and a surface polysaccharide are needed for translocation (26), and the nonswarming mutants lacking the flagellar proteins FlhA and FlgN have confirmed that cell elongation and upregulation of flagellar and virulence genes are mechanistically coupled (25)(26)(27). Artificial overproduction of the flagellar regulatory master operon flhDC in Serratia and Proteus cells induces elongation and hyperflagellation, suggesting that it could be a primary site for swarm cell induction (19,22), but no regulatory component has been identified that specifically couples physiological or environmental signals to swarm cell changes in gene expression. We report a mini-Tn5Cm mutant of P. mirabilis that is unable to swarm and show that the mutation interrupts the lrp gene encoding a global regulator, the leucine-responsive regulatory protein. MATERIALS AND METHODSMutagenesis and assays of swarming, motilit...

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Three New Regulators of Swarming inVibrio parahaemolyticus

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