Pseudomonas aeruginosa Magnesium Transporter MgtE Inhibits Type III Secretion System Gene Expression by Stimulating rsmYZ Transcription

Abstract

causes numerous acute and chronic opportunistic infections in humans. One of its most formidable weapons is a type III secretion system (T3SS), which injects powerful toxins directly into host cells. The toxins lead to cell dysfunction and, ultimately, cell death. Identification of regulatory pathways that control T3SS gene expression may lead to the discovery of novel therapeutics to treat infections. In a previous study, we found that expression of the magnesium transporter gene inhibits T3SS gene transcription. MgtE-dependent inhibition appeared to interfere with the synthesis or function of the master T3SS transcriptional activator ExsA, although the exact mechanism was unclear. We now demonstrate that expression acts through the GacAS two-component system to activate and transcription. This event ultimately leads to inhibition of translation. This inhibitory effect is specific to as translation of other genes in the operon is not inhibited by Moreover, our data reveal that MgtE acts solely through this pathway to regulate T3SS gene transcription. Our study reveals an important mechanism that may allow to fine-tune T3SS activity in response to certain environmental stimuli. The type III secretion system (T3SS) is a critical virulence factor utilized by numerous Gram-negative bacteria, including , to intoxicate and kill host cells. Elucidating T3SS regulatory mechanisms may uncover targets for novel anti- therapeutics and provide deeper understanding of bacterial pathogenesis. We previously found that the magnesium transporter MgtE inhibits T3SS gene transcription in In this study, we describe the mechanism of MgtE-dependent inhibition of the T3SS. Our report also illustrates how MgtE might respond to environmental cues, such as magnesium levels, to fine-tune T3SS gene expression.

RsmV, a Small Noncoding Regulatory RNA in Pseudomonas aeruginosa That Sequesters RsmA and RsmF from Target mRNAs

“…MvaT, a H-NS like protein, binds AϩT-rich regions of DNA and silences rsmZ transcription, while BswR, a transcriptional regulator, counteracts negative regulation of rsmZ by MvaT (24,42). Recently, MgtE, a magnesium transporter, was shown to alter rsmY and rsmZ transcription, though a mechanism of action is yet to be defined (43).…”

RsmV a small non-coding regulatory RNA in Pseudomonas aeruginosa that sequesters RsmA and RsmF from target mRNAs

“…MvaT, a H-NS like protein, binds A+T rich regions of DNA and silences rsmZ transcription, while BswR, a transcriptional regulator, counteracts negative regulation of rsmZ by MvaT (20, 21). Recently, MgtE, a magnesium transporter, was shown to alter rsmY and rsmZ transcription, yet a mechanism of action is yet to be defined (25).…”

Small Noncoding Regulatory RNAs from Pseudomonas aeruginosa and Burkholderia cepacia Complex

“…RsmA appears to control T3SS gene expression by increasing exsA translation through an undetermined mechanism. ExsA is the master transcription factor of all T3SS genes [73]. So, RsmA regulates the switching from planktonic (acute infection) to biofilm (chronic infection) phenotype.…”

“…MgtE, a magnesium transporter, was demonstrated to play a role in the inhibition of the T3SS transcriptional activator ExsA. The negative regulation is mediated by expression of RsmY and RsmZ, most likely though the TCS GacA/GacS [73]. The polynucleotide phosphorylase (PNPase), which is involved in the regulation of multiple virulence factors like T3SS, T6SS and pili biosynthesis, plays an important role in RsmY/Z stability.…”