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Updated: Jan 28, 2026

Author Spotlight: Advancements in Understanding and Combatting Shigella Infections
Published on: February 9, 2024
The MFS efflux pump EmrKY contributes to the survival of Shigella within macrophages
Martina Pasqua1, Milena Grossi1, Sara Scinicariello1
1Istituto Pasteur Italia, Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, Rome, Italy.
Abstract:
Efflux pumps are membrane protein complexes conserved in all living organisms. Beyond being involved in antibiotic extrusion in several bacteria, efflux pumps are emerging as relevant players in pathogen-host interactions. We have investigated on the possible role of the efflux pump network in Shigella flexneri, the etiological agent of bacillary dysentery. We have found that S. flexneri has retained 14 of the 20 pumps characterized in Escherichia coli and that their expression is differentially modulated during the intracellular life of Shigella. In particular, the emrKY operon, encoding an efflux pump of the Major Facilitator Superfamily, is specifically and highly induced in Shigella-infected U937 macrophage-like cells and is activated in response to a combination of high K+ and acidic pH, which are sensed by the EvgS/EvgA two-component system. Notably, we show that following S. flexneri infection, macrophage cytosol undergoes a mild reduction of intracellular pH, permitting EvgA to trigger the emrKY activation. Finally, we present data suggesting that EmrKY is required for the survival of Shigella in the harsh macrophage environment, highlighting for the first time the key role of an efflux pump during the Shigella invasive process.
Insights
Shigella flexneri utilizes the EmrKY efflux pump during host cell invasion. This pump is activated by acidic conditions within macrophages, aiding bacterial survival in the host environment.
Area of Science:
- Microbiology
- Molecular Biology
- Cell Biology
Background:
- Efflux pumps are vital membrane proteins in all organisms.
- They are implicated in antibiotic resistance and pathogen-host interactions.
- Shigella flexneri causes bacillary dysentery.
Purpose of the Study:
- To investigate the role of the efflux pump network in Shigella flexneri.
- To understand the regulation and function of specific efflux pumps during infection.
Main Methods:
- Comparative analysis of efflux pumps in S. flexneri and E. coli.
- Gene expression analysis during intracellular infection.
- Investigating the role of the EvgS/EvgA two-component system.
- Assessing bacterial survival in macrophage-like cells.
Main Results:
- S. flexneri possesses 14 characterized efflux pumps.
- The emrKY operon is highly induced in infected macrophages.
- EmrKY expression is regulated by high K+, acidic pH, and the EvgS/EvgA system.
- Intracellular pH reduction in macrophages triggers emrKY activation.
- EmrKY is crucial for S. flexneri survival within macrophages.
Conclusions:
- The EmrKY efflux pump plays a critical role in Shigella flexneri's survival during host cell invasion.
- Efflux pumps are key virulence factors in bacterial pathogenesis.
- This study reveals a novel mechanism of bacterial adaptation within the host environment.
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