Biology subjects

Perron, K.

Publications and source records attributed to Perron, K..

3 recordsLinked to original sources

bioRxiv2026

A periplasmic regulator establishes adaptive impermeability to control carbapenem entry

Outer-membrane permeability is a major determinant of antibiotic susceptibility in Gram-negative bacteria and is generally thought to be controlled through transcriptional regulation of porin expression. Here we identify the small periplasmic protein PtrA as a regulator of OprD-dependent carbapenem permeability in Pseudomonas aeruginosa. PtrA promotes imipenem resistance without altering OprD abundance, associates with OprD-containing membrane complexes and reduces intracellular imipenem entry. Using zinc and copper as complementary physiological signals, we show that PtrA-mediated permeability control is mechanistically distinct from CzcRS-dependent repression of oprD and precedes transcriptional porin depletion. These findings define a two-phase mechanism in which rapid periplasmic regulation provides an immediate adaptive response before transcriptional remodeling of the outer membrane. Our work identifies adaptive impermeability as a previously unrecognized mechanism linking environmental sensing to dynamic control of bacterial outer-membrane permeability.

microbiology↗

bioRxiv2022

A Zur-mediated transcriptional regulation of the zinc export system

The control of cellular zinc (Zn) concentrations by dedicated import and export systems is essential for the survival and virulence of Pseudomonas aeruginosa. The transcription of its many Zn transporters is therefore tightly regulated by a known set of transcription factors involved in either the import or the export of Zn. In this work, we show that the Zur protein, a well-known repressor of Zn import, plays a dual role and functions in both import and export processes. In a situation of Zn excess, Zur represses Zn entry, but also activates the transcription of czcR, a positive regulator of the Zn export system. To achieve this, Zur binds at two sites, located by DNA footprinting in the region downstream the czcR transcription start site. In agreement with this regulation, a delay in induction of the efflux system is observed in the absence of Zur and Zn resistance is affected. The discovery of this regulation highlights a new role of Zur as global regulator of Zn homeostasis in P. aeruginosa disclosing an important link between Zur and zinc export.

microbiology↗

bioRxiv2021

Global analysis of the zinc homeostasis network in Pseudomonas aeruginosa and its gene expression dynamics

Zinc is one of the most important trace elements for life and its deficiency, like its excess, can be fatal. In the bacterial opportunistic pathogen Pseudomonas aeruginosa, Zn homeostasis is not only required for survival, but also for virulence and antibiotic resistance. Thus, the bacterium possesses multiple Zn import/export/storage systems. In this work, we determine the expression dynamics of the entire P. aeruginosa Zn homeostasis network at both transcript and protein levels. Precisely, we followed the switch from a Zn-deficient environment, mimicking the initial immune strategy to counteract bacterial infections, to a Zn-rich environment, representing the phagocyte metal boost used to eliminate an engulfed pathogen. Thanks to the use of the NanoString technology, we timed the global silencing of Zn import systems and the orchestrated induction of Zn export systems. We show that the induction of Zn export systems is hierarchically organized as a function of their impact on Zn homeostasis. Moreover, we identify PA2807 as a novel Zn resistance component in P. aeruginosa and highlight new regulatory links among Zn-homeostasis systems. Altogether, this work unveils a sophisticated and adaptive homeostasis network, which complexity is key in determining a pathogen spread in the environment and during host-colonization.

microbiology↗