© Florence Vincent
Modern medicine is now faced with the increasingly frequent appearance of pathogenic bacteria resistant to antibiotic treatments. The consequences are dire for society and, more particularly, for people infected with these bacteria. In an article published in the journal Structure, scientists describe the three-dimensional structure of GacS, a key protein in the development of resistance in Pseudomonas aeruginosa.
One of the main reasons why these resistant bacteria wield a “shield” capable of preventing the action of antibiotic therapy, is their ability to live in the community, within a bacterial biofilm * (* set of bacteria covered by a matrix composed of DNA, proteins and polysaccharides).
These last decades, Pseudomonas aeruginosa (PA) was appointed agent pathogen (The term pathogenic (from the Greek παθογ? Νεια! …) patients with major infection admitted to hospital for a cancer (Cancer is a disease characterized by abnormal cell proliferation …)the cystic fibrosis (Mucoviscidose (for “viscous mucus disease” in French) or …) as well as severe burns. The PA is able to do this ride (The genus Passer was created by the French zoologist Mathurin Jacques …) of a mode of life (Life is the name given 🙂 planktonic (free swimming) – during which an acute infection follows, and during which the eradication of bacteria is possible – to a sedentary lifestyle (within the biofilm) due to chronic infection, resistant to long-lasting antibiotic treatments duration. Chronic infection affects more than 80% of adult patients with cystic fibrosis. It is the leading cause of morbidity and mortality.
The GacS / GacA system: GacS is a histidine kinase (HK) that recognizes a signal (General terms A signal is a simplified and generally coded message. There is …) environmental. It then transmits this signal inside the bacterium (Bacteria (bacteria) are prokaryotic single-celled living organisms, characterized …). This process is used to trigger a response functional (In mathematics, the term functional refers to certain functions ….) using the protein (A protein is a biological macromolecule composed of one or more …) GacA partner. GacS is a membrane protein composed of seven functional subdomains. She is involved in the development of biofilm (A biofilm is a more or less complex and symbiotic community of microorganisms …) of PA But its action is regulated by other proteins. In particular, the RetS protein that interferes with GacS signaling by interacting directly with it. This action blocks the development of the biofilm and promotes acute infection.
Therefore, GacS and RetS together represent a switch (A switch (derivative of breakdown) is a device or organ, physical or virtual, which allows …) molecular in PA that would move from a chronic infection modality to an acute phase.
Scientists established the 135Å three-dimensional structure length (The length of an object is the distance between its two furthest ends …)of 3 cytoplasmic domains of GacS, and highlight a new one interface (An interface is an area, real or virtual, that separates two elements. The interface …) frominteraction (An interaction is an exchange of information, affect or energy between two agents within …) between GacS and RetS, as well as a new essential domain for theactivities (The term activity can refer to a profession.) of GacS but whose function remains unknown.
These results allow us to learn more about the function of this large HK in PA that has always been theobject (In general, the word object (from the Latin objectum, 1361) designates an entity defined in …) lots of attention from the community scientific (A scientist is a person who devotes himself to the study of one or more sciences and who …) through its strategic role, as a conductor, in phase (The word phase can have different meanings, it is used in different fields and …) early development of the biofilm. They open to field (A field corresponds to a notion of defined space 🙂 from Research (Scientific research primarily refers to all actions undertaken with a view to …) little explored until now due to lack of information at the molecular level and which could in the future allow the development of therapeutic molecules capable of controlling the way the PA is infected.
Illustration of the role played by GacS (3D structure resolved in this study, shown in orange) in the development of the bacterial biofilm.
© Florence (Florence (in Italian Firenze) is a city in Italy, the capital of the Tuscany region and …) vincent
To know more:
Insights into the atypical activity of the autokinase of the Pseudomonas aeruginosa GacS histidine kinase and its interaction with RetS
Firas Fadel, Violla Bassim, vanessa (The genus Vanessa includes butterflies from the Nymphalidae family. This species …) I. Francis, Steven L. Porter, Thomas Botzanowski, Pierre Legrand, Maria Maté Perez, Yves Bourne, Sarah Cianferani, Florence Vincent.
Structure June 28, 2022. DOI: https://doi.org/10.1016/j.str.2022.06.002
Architecture and function of biological macromolecules laboratory – AFMB (CNRS / University of Aix-Marseille) – 163 avenue (An avenue is a large urban street. In principle it is tree-lined and leads to a …) by Luminy.
Case 932. 13288 Marseille cedex 09.
Florence Vincent – Researcher at the Laboratory of Architecture and Function of Biological Macromolecules (AFMB) – fvincent.cnr (The National Center for Scientific Research, better known by the acronym CNRS, is the largest …) on univ-amur.fr
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