Know more

Our use of cookies

Cookies are a set of data stored on a user’s device when the user browses a web site. The data is in a file containing an ID number, the name of the server which deposited it and, in some cases, an expiry date. We use cookies to record information about your visit, language of preference, and other parameters on the site in order to optimise your next visit and make the site even more useful to you.

To improve your experience, we use cookies to store certain browsing information and provide secure navigation, and to collect statistics with a view to improve the site’s features. For a complete list of the cookies we use, download “Ghostery”, a free plug-in for browsers which can detect, and, in some cases, block cookies.

Ghostery is available here for free: https://www.ghostery.com/fr/products/

You can also visit the CNIL web site for instructions on how to configure your browser to manage cookie storage on your device.

In the case of third-party advertising cookies, you can also visit the following site: http://www.youronlinechoices.com/fr/controler-ses-cookies/, offered by digital advertising professionals within the European Digital Advertising Alliance (EDAA). From the site, you can deny or accept the cookies used by advertising professionals who are members.

It is also possible to block certain third-party cookies directly via publishers:

Cookie type

Means of blocking

Analytical and performance cookies

Realytics
Google Analytics
Spoteffects
Optimizely

Targeted advertising cookies

DoubleClick
Mediarithmics

The following types of cookies may be used on our websites:

Mandatory cookies

Functional cookies

Social media and advertising cookies

These cookies are needed to ensure the proper functioning of the site and cannot be disabled. They help ensure a secure connection and the basic availability of our website.

These cookies allow us to analyse site use in order to measure and optimise performance. They allow us to store your sign-in information and display the different components of our website in a more coherent way.

These cookies are used by advertising agencies such as Google and by social media sites such as LinkedIn and Facebook. Among other things, they allow pages to be shared on social media, the posting of comments, and the publication (on our site or elsewhere) of ads that reflect your centres of interest.

Our EZPublish content management system (CMS) uses CAS and PHP session cookies and the New Relic cookie for monitoring purposes (IP, response times).

These cookies are deleted at the end of the browsing session (when you log off or close your browser window)

Our EZPublish content management system (CMS) uses the XiTi cookie to measure traffic. Our service provider is AT Internet. This company stores data (IPs, date and time of access, length of the visit and pages viewed) for six months.

Our EZPublish content management system (CMS) does not use this type of cookie.

For more information about the cookies we use, contact INRA’s Data Protection Officer by email at cil-dpo@inra.fr or by post at:

INRA
24, chemin de Borde Rouge –Auzeville – CS52627
31326 Castanet Tolosan CEDEX - France

Dernière mise à jour : Mai 2018

Menu INRA

Home page

Micalis

HEME - Group leader : Delphine LECHARDEUR

Delphine 3

CR (HDR)

+33 1 3465 2091

mail : Delphine LECHARDEUR

Research project :

Role of heme in the host-pathogen interaction

Heme or iron-porphyrin is a multifunctional molecule that acts as a cofactor in species ranging from humans to bacteria for two vital cell activities: respiration and elimination of ROS. Heme is also an important iron source for pathogenic bacteria. Associated with hemoglobin within the blood of vertebrates, heme is the main iron reservoir within host.

DL image 1

Because of its redox activity (Fenton reaction), heme si also highly toxic. During infection, pathogens are therefore facing heme toxicity while depending on it for their survival in the host environment.

Our research activities focus on the mechanisms expressed by Gram-positive pathogens (Streptococcus agalactiae and Staphylococcus aureus) to manage host heme during colonization and infection. We are also interested in understanding heme interactions with the food bacteria Lactococcus lactis.

DL image 2

Our projects:

1-The mechanisms of heme homeostasis by efflux and its regulation

Most bacteria have evolved sophisticated machineries to scavenge heme from the host. However, due to its high reactivity, an excess of heme is toxic for bacteria. Thus, the ability to accurately regulates intracellular heme concentration is critical to many pathogens. A conserved mechanism of heme detoxification in several Gram-positive pathogens relies on the HrtBA efflux pump. This specific ABC transporter enables pathogens to secrete intracellular heme. We recently demonstrated the relationship between menaquinone induced membrane accumulation of heme and HrtBA activity. Our hypothesis is that HrtBA heme effux mechanism could be related to that of a vacuum cleaner or a flippase transporters such as MDR pumps.

2- Heme stress sensing by Gram-positive bacteria

In numerous Gram-positive pathogens, heme efflux is regulated by a two component system (TCS) called HssRS (Hss; heme sensing system), where HssR is a transcriptional regulator and HssS is its cognate transmembrane histidine kinase. HssS is presumed to be the heme sensor that activates HssR through phosphorylation. The coordinated expression of HssRS and HrtBA enables pathogens to withstand high heme concentrations, indicating a central role of efflux in heme homeostasis. Our project is aimed at understanding the mechanisms of heme recognition and signal transduction by the HssS membrane sensor in our 2 model bacteria Staphylococcus aureus and Streptococcus agalactiae.

We also recently identified a new pathway for the regulation of HrtBA expression in Lactococcus lactis which relies on a cytoplasmic hemoprotein HrtR, a TetR family transcriptional regulator. This regulation pathway is present in food and commensal bacteria whereas the HssRS two component system is widespread among pathogens.

DL image 3

3- Visualization of the role of host heme on pathogens during infection

Using bioluminescent bacteria and heme-responsive reporters for in vivo imaging, we constructed a series of strains (Lactococcus lactis, Staphylococcusaureus, Enterococcus faecalis and Streptococcus agalactiae) to follow the infection in a mouse model by real time imaging (IVIS).  We recently show that the capacity of S. agalactiae to overcome heme toxicity is required for successful infection, particularly in blood-rich organs. Host heme is simultaneously required, as visualized by a generalized infection defect of a respiration-negative mutant. We conclude that S. agalactiae response to heme is organ-dependent, and its efflux may be particularly relevant in late stages of infection.

DL image 4

 

Financial supports

This work has been recently supported by the ANR HemeStockExchange (2013-2017) and ANR ALIAS (Aliments, Alimentation et santé) ANR-11-IDEX-0003-02 (end 2016).  Our research project is currently supported by the ANR HemeDetox (2018-2021).

ligne

Bibliography (2015-2018) :

Joubert L, Dagieu JB, Fernandez A, Derré-Bobillot A, Borezée-Durant E, Fleurot I, Gruss A, Lechardeur D. Visualization of the role of host heme on the virulence of the heme auxotroph Streptococcus agalactiae. Sci Rep. 2017 Jan 16

ligne

Collaborations :

H. Blottière (INRA, Jouy-en-Josas)

A. Firon (Institut Pasteur, Paris) ; P. Trieu-Cuot (Institut Pasteur, Paris) ; P. Arnoux (CEA, Cadarache)

L. Hederstedt (Lund, Sweden)

ligne

Research staff :

Damien LIPUMA

Read more

Vincent SAILLANT

Read more