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Regulatory RNAs and Nutritional immunity

Investigator: Dr. David Lalaouna

The host immune system use different defense strategies to fight against pathogenic organisms such as Staphylococcus aureus. Since metals are crucial micronutrients for all forms of life, the competition for access to metals between the host and the pathogen is one of the key factors that determines the outcome of the infection. Neutrophils, for example, deploy metal-binding effectors, such as calprotectin, to reduce the bioavailability of essential metals at the infection sites starving intruders. Iron, manganese, and zinc are particularly targeted by this strategy, commonly known as “nutritional immunity.” In this war for resources, S. aureus has developed effective countermeasures to maintain the homeostasis of these metals, where regulatory RNAs play a crucial role.

Our team discovered and characterized the conductor of the response to manganese (Mn) scarcity in S. aureus (Lalaouna et al., 2019). The regulatory RNA RsaC spares intracellular manganese by repressing Mn-dependent but non-essential proteins such as superoxide dismutase A (SodA). In parallel, RsaC plays a decisive role in the response to oxidative stress by promoting an alternative pathway for detoxification of reactive oxygen species (e.g., O2 and H2O2) produced by the immune system to eradicate S. aureus. Indeed, RsaC promotes an iron-dependent response through SodM. The regulatory RNA RsaC also modulates other metallo-systems, as well as the synthesis of different virulence factors.

S. aureus finely regulates the intracellular concentration of other essential metals. Besides RsaC, our group have identified regulatory RNAs involved in the homeostasis of iron and zinc. This discovery reinforces the central role of regulatory RNAs in the adaptation to metal-dependent immune defenses and virulence in S. aureus.

Charbonnier M, González-Espinoza G, Kehl-Fie TE and Lalaouna D (2022). Battle for Metals: Regulatory RNAs at the Front Line. Front. Cell. Infect. Microbiol. 12:952948 [Open Access]

Lalaouna D and Romby P (2020). Manganese: The Battle of the Two Armies. Project Repository Journal 6:100-101 [Open Access]

Lalaouna D, Baude J, Wu Z, Tomasini A, Chicher J, Marzi S, Vandenesch F, Romby P, Caldelari I and Moreau K (2019). RsaC sRNA modulates the oxidative stress response of Staphylococcus aureus during manganese starvation. Nucleic Acids Res. 47(18):9871-9887 [Open Access]

Haffner F, Couturier M. and Lalaouna D (2020). The art of escaping one’s immune system: A portrait of the bug S. aureus. Esperluette [Link]

Moreau K and Caldelari I (2019). Un ARN régulateur du staphylocoque pour lutter contre le stress oxydatif. CNRS INSB [Link]

Pr. Thomas Kehl-Fie – University of Illinois at Urbana-Champaign (USA) [Link]

Pr. Hanah Margalit – The Hebrew University of Jerusalem (Israël) [Link]

Pr. Karen Moreau and Pr. François Vandenesch – International Center for Infectiology Research (Lyon, France) [Link]

Thomas Jefferson Fund 2021 – FACE Foundation

Attractivité IdEX 2021 – University of Strasbourg

ANR JCJC 2020 – French National Research Agency [Link]

Marie Skłodowska-Curie Individual Fellowship 2016 – European commission [Link]