Cell differentiation of Proteus mirabilis is initiated by glutamine, a specific chemoattractant for swarming cells.
Swarming by Proteus mirabilis involves differentiation of typical short vegetative rods into filamentous hyperflagellated swarm cells which undergo cycles of rapid and co-ordinated population migration across surfaces and exhibit high levels of virulence gene expression. By supplementing a minimal growth medium (MGM) unable to support swarming migration we identified a single amino acid, glutamine, as sufficient to signal initiation of cell differentiation and migration. Bacteria isolated from the migrating edge of colonies grown for 8 h with glutamine as the only amino acid were filamentous and synthesized the characteristic high levels of flagellin and haemolysin. In contrast, addition of the other 19 common amino acids (excluding glutamine) individually or in combination did not initiate differentiation even after 24 h, cells remaining typical vegetative rods with basal levels of haemolysin and flagellin. The glutamine analogue gamma-glutamyl hydroxamate (GH) inhibited swarming but not growth of P. mirabilis on glutamine MGM and transposon mutants defective in glutamine uptake retained their response to glutamine signalling and its inhibition by GH, suggesting that differentiation signalling by glutamine may be transduced independently of the cellular glutamine transport system. Levels of mRNA transcribed from the haemolysin (hpmA) and flagellin (fliC) genes were low in vegetative cells grown on MGM without glutamine or with glutamine and GH, but were specifically increased c. 40-fold during glutamine-dependent differentiation. In liquid glutamine-MGM cultures, differentiation to filamentous hyper-flagellated hyper-haemolytic swarm cells occurred early in the exponential phase of growth, and increased concomitantly with the concentration of glutamine from a 0.1 mM threshold up to 10 mM.(ABSTRACT TRUNCATED AT 250 WORDS)
Cambridge University Department of Pathology, UK.
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D001483:Base Sequence; D001692:Biological Transport; D002454:Cell Differentiation; D002465:Cell Movement / Q000187:drug effects; D002630:Chemotactic Factors / Q000494:pharmacology*; D002633:Chemotaxis / Q000235:genetics; D005408:Flagellin / Q000096:biosynthesis; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology; D005973:Glutamine / Q000494:pharmacology*; D006460:Hemolysin Proteins / Q000096:biosynthesis; D006877:Hydroxamic Acids / Q000494:pharmacology; D008969:Molecular Sequence Data; D011513:Proteus mirabilis / Q000166:cytology / Q000187:drug effects* / Q000472:pathogenicity; D014774:Virulence
D002630:Chemotactic Factors; D005971:Glutamates; D006460:Hemolysin Proteins; D006877:Hydroxamic Acids; D005973:Glutamine; D005408:Flagellin; C001296:L-glutamic acid-gamma-hydrazide; C050614:glutamate-gamma-hydroxamic acid