GRUPOS DE INVESTIGACIÓN

Transducción de Señales en Bacterias Patógenas

RESUMEN

Las bacterias tienen la capacidad de detectar e integrar diferentes señales del medioambiente para adaptarse rápidamente y sobrevivir en esos entornos. La investigación que se lleva adelante en nuestro laboratorio se centra en el análisis de mecanismos de señalización ambiental que modulan la expresión de factores requeridos por el patógeno Salmonella enterica para establecer la infección, así como para sobrevivir en el medio ambiente, donde se encuentra contaminando agua y alimentos. Esto incluye el análisis de las señales externas que modulan la actividad biológica de sistemas de regulación transcripcional, y la caracterización funcional de estos sistemas y de los genes bajo su control. Nos proponemos además utilizar estas vías de señalización para generar herramientas con utilidad tecnológica.

DIRECTORES/AS DE GRUPO

DIRECTORES/AS DE PROYECTO

BECARIOS/AS DOCTORALES
  • Peña Buitrago, Sebastian

BECARIOS/AS POST-DOCTORALES

TESINISTAS
  • Reinero, Juan Jose

LÍNEA DE INVESTIGACIÓN

1.

The control of the transition between motile life and the establishment of sessile, communal life is essential for bacterial survival in the environment, and for the establishment of numerous infections. We have identified new Salmonella-specific regulators linked to this transition and detected that at least one of them is required for its virulence. We are currently evaluating their specific function, and their interaction with other regulators that modulate this transition. In addition to establish how these factors modify the structure of the biofilm, we are investigating the signal(s) to which they respond, and their regulatory targets. This will allow us to elucidate the role of each of these regulators in the decision between planktonic and sessile life. The results of these studies will allow us to understand strategies developed by Salmonella to adapt to changes in the environment that occur fundamentally during infection (see Figure 1). In addition, they will allow to understand the mechanisms by which a microbe can reprogram its way of life, altering its gene expression in response to environmental as well as intracellular signals. Our findings are expected to provide insight into the modulation of biofilm formation in different bacterial species, in addition to generating tools of potential technological utility in the design of new antimicrobial agents.

2.

Copper is an essential although highly toxic metal. Our group is focused on the characterization of the copper-recognition systems that control the expression of factors involved in the control of metal homeostasis in Salmonella. Extensive evidence indicates that these systems are relevant for the virulence of intracellular pathogens such as Mycobacterium tuberculosis and Salmonella enterica. Among these systems, we focus particularly on the characterization of transcriptional regulators such as CueR, GolS and CpxR/CpxA, and the factors controlled by these regulators that provide resistance to the metal or mitigate the damage caused by it (see Figure 2). We are currently carrying out the functional and structural analysis of Salmonella-specific factors controlled by these regulators that are located in the bacterial envelope, such as the periplasmic copper-binding protein, CueP, and the complex of thiol-oxidoreductases and accessory proteins, ScsABCD, that confer resistance to copper and redox stress. In addition, we are actively working on the identification of new envelope factors linked to this pathogen’s Cu homeostasis. We aim to identify new therapeutic targets for the treatment and/or control of Salmonella infections in both humans and animals of commercial importance.

3.

Whole bacterial biosensors are genetically-modified microorganisms that couple the detection of a given compound to the production of a quantifiable signal. In addition to their low cost and its technical simplicity, they report the bioavailable fraction of the metal, and therefore they are especially useful for evaluating environmental risk and water quality. We have previously developed the first fluorescent bacterial biosensor for the specific detection of gold, and also a mercury-selective biosensor as well as others that detect a wide spectrum of harmful metals to humans and to the ecosystem (see Figure 2). Aiming to generating new tools for the specific detection of other toxic metals, we are modifying the central component of our designed biodetection platform, the GolS sensor/regulator, and the bacterial chassis for the simultaneous bio-removal of these contaminants. Also, we are applying immobilization and preservation strategies of the bioreporting bacteria to enable the development of instruments or devices for in-field detection of these toxics. In parallel, we are characterizing variants of GolS and of its structural and functional analog, CueR, to understand the molecular bases of their interaction with different metal ions and how the input signal is transmitted to modulate the expression of their target genes. This knowledge will contribute to benefit the environment as well as to health care.

IMÁGENES DE NUESTRAS INVESTIGACIONES

PUBLICACIONES Y PATENTES

Evolution of Copper Homeostasis and Virulence in Salmonella.

Front Microbiol. 13:823176. Méndez AAE, Mendoza JI, Echarren ML, Terán I, Checa SK, Soncini FC. (2022).

Evolution of Copper Homeostasis and Virulence in Salmonella.

Front Microbiol. 13:823176. Méndez AAE, Mendoza JI, Echarren ML, Terán I, Checa SK, Soncini FC. (2022).
DOI

Balance between bacterial extracellular matrix production and intramacrophage proliferation by a Salmonella-specific SPI-2-encoded transcription factor.

Mol Microbiol. 116(4):1022-1032. Echarren ML, Figueroa NR, Vitor-Horen L, Pucciarelli MG, García-Del Portillo F, Soncini FC. (2021).

Balance between bacterial extracellular matrix production and intramacrophage proliferation by a Salmonella-specific SPI-2-encoded transcription factor.

Mol Microbiol. 116(4):1022-1032. Echarren ML, Figueroa NR, Vitor-Horen L, Pucciarelli MG, García-Del Portillo F, Soncini FC. (2021).
DOI

Copper Handling in the Salmonella Cell Envelope and Its Impact on Virulence.

Trends Microbiol. 29(5):384-387. Checa SK, Giri GF, Espariz M, Argüello JM, Soncini FC. (2021).

Copper Handling in the Salmonella Cell Envelope and Its Impact on Virulence.

Trends Microbiol. 29(5):384-387. Checa SK, Giri GF, Espariz M, Argüello JM, Soncini FC. (2021).
DOI

Engineering of a Au-sensor to develop a Hg-specific, sensitive and robust whole-cell biosensor for on-site water monitoring.

Chem Commun (Camb). 56(48):6590-6593. Mendoza JI , Soncini FC , Checa SK. (2020).

Engineering of a Au-sensor to develop a Hg-specific, sensitive and robust whole-cell biosensor for on-site water monitoring.

Chem Commun (Camb). 56(48):6590-6593. Mendoza JI , Soncini FC , Checa SK. (2020).
DOI

CpxR/CpxA Controls scsABCD Transcription To Counteract Copper and Oxidative Stress in Salmonella enterica Serovar Typhimurium.

J Bacteriol. 200(16):e00126-18. López C, Checa SK, Soncini FC. (2018).

CpxR/CpxA Controls scsABCD Transcription To Counteract Copper and Oxidative Stress in Salmonella enterica Serovar Typhimurium.

J Bacteriol. 200(16):e00126-18. López C, Checa SK, Soncini FC. (2018).
DOI

contacto@conicet.gov.ar

Sede CCT Rosario

Ocampo y Esmeralda, Predio CONICET-Rosario
2000 Rosario, Santa Fe, Argentina
Tel. 54-341-4237070 / 4237500 / 4237200

Sede Facultad de Ciencias Bioquímicas y Farmacéuticas

Universidad Nacional de Rosario - Suipacha 531
2000 Rosario, Santa Fe, Argentina
Tel. +54 341 4350596 / 4350661 / 4351235

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