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HEIndividual fellowship2022–2024

BARTAS · Revealing the BActerial Response to Temperature and Antibiotics Stress via multiscale imaging

Horizon Europe — Marie Skłodowska-Curie Actions

Duration
2022-10-01 → 2024-09-30
EU contribution
€211,755
Participants
1
Scheme
HORIZON-TMA-MSCA-PF-EF

Lines connect the coordinator with its partners.

Results in brief

Revealing the BActerial Response to Temperature and Antibiotics Stress via multiscale imaging

Bacteria are highly adaptable organisms capable of surviving challenging environmental conditions, including temperature changes, acidity, exposure to harmful substances, DNA damage, and nutrient shortages. This adaptability makes bacterial infections difficult to treat and contributes to the growing crisis of antibiotic resistance. Currently, antibiotic resistance causes 700,000 deaths annually, a number projected to rise to 10 million by 2050 without urgent intervention. The BARTAS project (Revealing the Bacterial Response to Temperature and Antibiotics Stress via Multiscale Imaging) investigated how bacteria respond to the combined stresses of heat and antibiotics at the single-cell level, using advanced imaging technologies to uncover new insights into their survival mechanisms. When the body fights an infection, it often raises its temperature, causing a fever. This heat puts bacteria under stress, forcing them to adapt quickly to survive and grow. If they fail to adapt, the heat could disrupt essential functions such as maintaining cell walls, producing proteins, and preserving DNA. In addition to heat, antibiotics challenge bacteria by targeting critical survival mechanisms. However, the interaction between heat stress and antibiotic effectiveness remains poorly understood. BARTAS addressed this knowledge gap by combining microfluidic and microscopy techniques to explore bacterial survival mechanisms under these stresses.

Data: CORDIS, © European Union

Project objective

Antibiotic resistance is one of the biggest scientific and health challenges of our time. If actions are not taken, antibiotics resistance infections will become the first cause of death by 2050. One of the most common signs of bacterial infection is a rapid increase of the host temperature that exposes bacteria to a heat shock (HS). To survive and quickly adapt to this new environment, bacteria activate the synthesis of specific proteins, called heat shock proteins (HSPs). In E.coli, HSPs expression is mediated by the alternative sigma factor sigma32 (Sig32). The molecular processes that are associated with the bacterial stress responses induced by a combination of change in temperature and presence of antibiotics have not yet been investigated in detail due to the technical challenges of monitoring this combination of stresses with the necessary temporal and spatial accuracy. Cell-to-cell fluctuations in protein expression could affect single cells survival. Therefore, these processes should be studied with single cell precision. I propose to investigate bacterial responses to the combined stresses of temperature increase and antibiotics at single cell level in live E.coli using a combination of microfluidics and single molecule/super-resolution imaging. I will design and build a microfluid system able to control the stress landscape of temperature and antibiotic concentrations. This will allow me to study Sig32 expression during HS using fast-maturating fluorescent protein fusions. Next, I will monitor how HS affects proteins synthesis by measuring the diffusion changes of single ribosomal subunits (S30 and S50) during HS, using single particle tracking PALM. Finally, I will quantify the interplay between HS response and antibiotic susceptibility by monitoring Sig32 levels and the diffusion of ribosomal subunits. Taken together my results will provide for the first time a quantitative picture and a new framework to study bacterial response to multiple stresses.

Original text from CORDIS.

Participants

  • ECOLE POLYTECHNIQUE · PALAISEAU CEDEXCoordinatorFrance

Links

Data: CORDIS, © European Union