Biology subjects

Elgamoudi, B.

Publications and source records attributed to Elgamoudi, B..

2 recordsLinked to original sources

bioRxiv2025

Spatiotemporal-multimodal integration reveals BCG-induced skin-blood crosstalk

Tuberculosis (TB) remains the leading cause of infectious death. The Bacille Calmette-Guerin (BCG) vaccine has been the only licensed vaccine available for TB prevention. Despite BCG being administered intradermally for over a century to >100 million individuals annually, the molecular events in the skin following BCG administration have not been investigated; as a result, measurable correlates of protection that could predict vaccine effectiveness already early after vaccination are lacking. Here we show that BCG immediately (within one day after vaccination) induces dynamic molecular waves that drive the acute human host response across space (layers of the skin and systemically in blood) and time (days). Integration of this data across space and time identified robust networks of interactive modules related to immune surveillance (e.g. Langerhans cells), cell trafficking (e.g. endothelial cells, ITGB5), and trained immunity (e.g. neutrophils, macrophages, {gamma}{delta}-T cell). Importantly, not only were we able to identify BCG-activated pathways associated with trained immunity such as mTOR signaling and glycolysis/gluconeogenesis, we were able to pinpoint the time-point and precise location (skin layer) of the initial activation of theses pathways. Combining tissue biopsies of human skin (spatial genomics) with liquid biopsies (cell-free blood plasma RNASeq) following BCG vaccination our data both confirmed known evidence (e.g. prominent {gamma}{delta}-T cell induction at the site of BCG administration; negative correlation of blood vs tissue myeloid-derived suppressor cells), but also generated promising new leads such as baseline levels of B cells, platelets and nuocytes in the skin prior to BCG administration predict eventual outcome, and that these predictive differences in baseline cellular composition can be captured non-invasively using high resolution images of the site of injection (dermatoscopy). Given this data represents the first holistic view of the acute molecular response to BCG in the skin in a human population at medium to high TB risk, we anticipate our findings of the immediate/early events following BCG vaccination, including non-invasive predictive assessment will support acceleration of vaccine development in the fight against TB.

systems biology↗

bioRxiv2021

The immunomodulatory dCache chemoreceptor TlpA of Helicobacter pylori binds multiple attractant and antagonistic ligands via distinct sites

The Helicobacter pylori chemoreceptor TlpA plays a role in dampening host inflammation during chronic stomach colonization. TlpA has a periplasmic dCache_1 domain, a structure that is capable of sensing many ligands; however, the only characterized TlpA signals are arginine, bicarbonate, and acid. To increase our understanding of TlpAs sensing profile, we screened for diverse TlpA ligands using ligand binding arrays. TlpA bound seven ligands with affinities in the low to middle micromolar ranges. Three of these ligands, arginine, fumarate, and cysteine, were TlpA-dependent chemoattractants, while the others elicited no response. Molecular docking experiments, site-directed point mutants, and competition surface plasmon resonance binding assays suggested that TlpA binds ligands via both the membrane-distal and -proximal dCache_1 binding pockets. Surprisingly, one of the non-active ligands, glucosamine, acted as a chemotaxis antagonist, preventing the chemotaxis response to chemoattractant ligands and acted to block binding of ligands irrespective of whether they bound the membrane-distal or -proximal dCache_1 subdomains. In total, these results suggest TlpA senses multiple attractant ligands as well as antagonist ones, an emerging theme in chemotaxis systems. ImportanceNumerous chemotactic bacterial pathogens depend on the ability to sense a diverse array of signals through chemoreceptors to achieve successful colonization and virulence within their host. The signals sensed by chemoreceptors, however, are not always fully understood. This is the case for TlpA, a dCache_1 chemoreceptor of H. pylori that enables the bacteria to induce less inflammation during chronic infections. H. pylori causes a significant global disease burden, which is driven by the development of gastric inflammation. Accordingly, it is essential to understand the processes by which H. pylori modulates host inflammation. This work uncovers the signals that TlpA can sense and highlights the underappreciated ability for regulating chemotactic responses by antagonistic chemoreceptor ligands, which is an emerging theme among other chemotactic systems.

microbiology↗