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Background  Many gram-negative bacterial pathogens employ Type III secretion systems (T3SS) to inject effector proteins into host cells in infectious processes.    Methodology/Principal Findings  By screening a transposon mutant library of  P. aeruginosa , we found that mutation of  spuDEFGH , which encode a major spermidine uptake system, abolished the expression of the  exsCEBA  operon that codes for key T3SS regulators under inducing conditions (low calcium). Whole genome microarray analysis revealed that inactivation of the spermidine uptake system significantly decreased the transcriptional expression of most, if not all, T3SS genes. Consistently, the spermidine uptake mutants showed decreased expression of the T3SS genes in responding to host cell extract and attenuated cytotoxicity. Furthermore, exogenous addition of spermidine to the wild type strain PAO1 enhanced the expression of  exsCEBA  and also the effector protein genes.    Conclusion/Significance  Cumulatively, these data have depicted a novel spermidine transporter-dependent signaling pathway, which appears to play an essential role in modulation of T3SS expression in  P. aeruginosa .

Modulation of Bacterial Type III Secretion System by a Spermidine Transporter Dependent Signaling Pathway