Biology subjects

Bleck, C.

Publications and source records attributed to Bleck, C..

3 recordsLinked to original sources

bioRxiv2023

Heterogeneous dual-metal control of Salmonella infection

Iron controls bacterial infections through diverse pathogen and host mechanisms that remain challenging to disentangle. Here, we determined how individual Salmonella cells access iron in infected mice. Our results showed that the iron transporter SLC11A1 restricted iron availability. However, many Salmonella bypassed this restriction by targeting macrophage endosomes that contained remnants of iron-rich red blood cells. These iron-replete bacteria dominated overall Salmonella growth and masked the relieve of iron-starved bacteria under iron overload. These data, combined with our previous discovery of magnesium deprivation as a primary mechanism for controlling Salmonella, reveal a heterogeneous dual-metal mechanism of nutritional immunity, and highlight the power of single-cell analyses under physiological in-vivo conditions to unravel complex anti-bacterial host mechanisms. One sentence summaryIron and magnesium limitations control distinct Salmonella subsets during infection.

cell biology↗

bioRxiv2020

β-Coronaviruses use lysosomal organelles for cellular egress.

{beta}-Coronaviruses are a family of positive-strand enveloped RNA viruses that include the severe acute respiratory syndrome-CoV2 (SARS-CoV2). While much is known regarding their cellular entry and replication pathways, their mode of egress remains uncertain; however, this is assumed to be via the biosynthetic secretory pathway by analogy to other enveloped viruses. Using imaging methodologies in combination with virus-specific reporters, we demonstrate that {beta}-Coronaviruses utilize lysosomal trafficking for egress from cells. This pathway is regulated by the Arf-like small GTPase Arl8b; thus, virus egress is insensitive to inhibitors of the biosynthetic secretory pathway. Coronavirus infection results in lysosome deacidification, inactivation of lysosomal degradation and disruption of antigen presentation pathways. This coronavirus-induced exploitation of lysosomes provides insights into the cellular and immunological abnormalities observed in patients and suggests new therapeutic modalities.

microbiology↗

bioRxiv2018

Cdc42 negatively regulates endocytosis during apical plasma membrane maintenance and development in mouse tubular organs in vivo

Lumen establishment and maintenance are fundamental for tubular organs physiological functions. Most of the studies investigating the mechanisms regulating this process have been carried out in cell cultures or in smaller organisms, whereas little has been done in mammalian model systems in vivo. Here we used the salivary glands of live mice to examine the role of the small GTPase Cdc42 in the regulation of the homeostasis of the intercellular canaliculi, a specialized apical domain of the acinar cells, where protein and fluid secretion occur. Depletion of Cdc42 in adult mice induced a significant expansion of the apical canaliculi, whereas depletion at late embryonic stages resulted in a complete inhibition of their post-natal formation. In addition, intravital subcellular microscopy revealed that reduced levels of Cdc42 affected membrane trafficking from and towards the plasma membrane, highlighting a novel role for Cdc42 in membrane remodeling through the negative regulation of selected endocytic pathways.

cell biology↗