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

What was studied?

This study tested how the magnesium transporter MgtE in Pseudomonas aeruginosa controls virulence by regulating type III secretion system (T3SS) gene expression. The authors treated the T3SS as the key “acute infection” weapon and asked why mgtE expression suppresses T3SS transcription. They specifically examined whether MgtE acts through extrinsic regulatory networks that control synthesis of ExsA, the master T3SS transcription factor, rather than through the intrinsic ExsD/ExsC/ExsE control switch that responds to secretion conditions.

Who was studied?

The study examined bacterial strains and regulatory circuits, not human participants. It used Pseudomonas aeruginosa strains PA103 and PA14 with reporter constructs that read out T3SS transcription and translation, along with targeted mutants in key regulators such as gacA, gacS, and rsmY/rsmZ. The work also used engineered strains that uncoupled native exsCEBA transcription from ExsA autoregulation so the team could isolate posttranscriptional effects on ExsA.

What were the most important findings?

The authors showed that MgtE suppresses T3SS gene expression by blocking ExsA translation, not by reducing exsA transcription or destabilizing exsA mRNA. When they forced constitutive exsCEBA transcription, mgtE expression still reduced ExsA-dependent reporter output, which placed the effect after transcription. Translational reporters pinpointed the effect as exsA-specific within the exsCEBA operon: mgtE repressed the exsA fusion but did not reduce exsC, exsE, or exsB translation, and exsA transcript levels actually increased with mgtE expression, which argues strongly for translational repression rather than mRNA loss. Mechanistically, mgtE increased transcription of the small RNAs rsmY and rsmZ by about twofold or more, and this increase required the GacAS two-component system because the effect disappeared in gacA or gacS mutants.

What are the greatest implications of this study?

This study supports magnesium-linked regulation as an anti-virulence control point in a major opportunistic pathogen. It suggests that environmental cues associated with infection settings, including low magnesium and antibiotic exposure that increase mgtE expression, can push P. aeruginosa to “fine-tune” T3SS output rather than keep it fully on, which matters for how the organism balances acute damage versus persistence. Clinically, the results elevate the GacAS–RsmY/Z network and ExsA translation control as actionable targets: interventions that mimic MgtE’s downstream signaling could reduce toxin injection without selecting as strongly for classic resistance because they do not aim to kill the bacteria.