tRNA modification enzyme MiaB connects environmental cues to activation of Pseudomonas aeruginosa type III secretion
Qiqi Lin1,2,3, Jiahui Huang1,2, Zhiqing Liu1,2
1Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Centre, South China Agricultural University, Guangzhou, China.
Abstract:
Pseudomonas aeruginosa, a major inhabitant of numerous environmental reservoirs, is a momentous opportunistic human pathogen associated with severe infections even death in the patients suffering from immune deficiencies or metabolic diseases. Type III secretion system (T3SS) employed by P. aeruginosa to inject effector proteins into host cells is one of the pivotal virulence factors pertaining to acute infections caused by this pathogen. Previous studies showed that P. aeruginosa T3SS is regulated by various environmental cues such as calcium concentration and the host signal spermidine. However, how T3SS is regulated and expressed particularly under the ever-changing environmental conditions remains largely elusive. In this study, we reported that a tRNA modification enzyme PA3980, designated as MiaB, positively regulated T3SS gene expression in P. aeruginosa and was essential for the induced cytotoxicity of human lung epithelial cells. Further genetic assays revealed that MiaB promoted T3SS gene expression by repressing the LadS-Gac/Rsm signaling pathway and through the T3SS master regulator ExsA. Interestingly, ladS, gacA, rsmY and rsmZ in the LadS-Gac/Rsm signaling pathway seemed potential targets under the independent regulation of MiaB. Moreover, expression of MiaB was found to be induced by the cAMP-dependent global regulator Vfr as well as the spermidine transporter-dependent signaling pathway and thereafter functioned to mediate their regulation on the T3SS gene expression. Together, these results revealed a novel regulatory mechanism for MiaB, with which it integrates different environmental cues to modulate T3SS gene expression in this important bacterial pathogen.
Insights
The tRNA modification enzyme MiaB positively regulates the Type III Secretion System (T3SS) in Pseudomonas aeruginosa, crucial for bacterial virulence. MiaB integrates environmental signals to control T3SS gene expression and cytotoxicity.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Pseudomonas aeruginosa is an opportunistic pathogen causing severe infections.
- The Type III Secretion System (T3SS) is a key virulence factor for P. aeruginosa.
- T3SS regulation by environmental cues like spermidine is known but incompletely understood.
Purpose of the Study:
- To elucidate the regulatory mechanism of T3SS gene expression in P. aeruginosa.
- To identify novel factors involved in T3SS regulation under changing environmental conditions.
Main Methods:
- Genetic assays were used to investigate the role of the tRNA modification enzyme PA3980 (MiaB).
- The study examined MiaB's interaction with the LadS-Gac/Rsm signaling pathway and the ExsA regulator.
- Expression analysis was performed to understand MiaB induction by Vfr and spermidine signaling.
Main Results:
- MiaB was identified as a positive regulator of T3SS gene expression and essential for P. aeruginosa cytotoxicity.
- MiaB represses the LadS-Gac/Rsm pathway and acts through the ExsA regulator to promote T3SS expression.
- MiaB expression is induced by Vfr and spermidine signaling, integrating these cues for T3SS regulation.
Conclusions:
- MiaB represents a novel regulatory mechanism for T3SS in P. aeruginosa.
- MiaB integrates environmental signals to modulate T3SS gene expression, impacting bacterial virulence.
- This finding provides new insights into the pathogenesis of P. aeruginosa infections.
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