In this study we analyze the the immune evasive pathogen C. albicans. The secreted pH regulated antigen 1 (Pra1) is a protease and cleaves C3, the key molecule for cell opsonization. The paradox of this mechanism is that this cleavage of C3 produces a molecule that is very similar to the opsonin C3b. At a first glance it is not obvious why this protease has a regulatory influence on the system. This paradox is to be deciphered with a mathematical model.
Model of the Pra1 interaction with the complement molecule C3 and its cleavage products.
Model of the interaction with the complement molecule and its cleavage products. Fluid phase binds to and cleaves it into fragments and . In addition, $Pra1^f$ binds to the cleavage products , , and and blocks their effector function. The molecule can bind to the cell surface like and there enhance complement activation via the -convertase of the alternative pathway or it is inactivated by regulators and cleaved to .
For this purpose, the existing DynaCoSys model is extended to include the dynamics of Pra1 and its cleavage products. The deviation of opsonization on the surface and of the molecules in the fluid around the cell will be analyzed in comparison to a cell without Pra1 secretion.
Jan-Philipp Praetorius*, Sophia U. J. Hitzler*, Mark S. Gresnigt#, Marc Thilo Figge#
The formation of hyphae is one of the most crucial virulence traits the human pathogenic fungus Candida albicans possesses. The assessment of hyphal length in response to various stimuli, such as exposure to human serum, provides valuable insights into the adaptation strategies of C. albicans to the host environment. Despite the increasing high-throughput capacity live-cell imaging and data generation, […]
The ability of pathogens to evade phagosomal killing is critical for their pathogenicity. Previously, we had identified the HscA effector protein in the clinically important fungal pathogen Aspergillus fumigatus, which redirects conidia-containing phagosomes from the degradative to the non-degradative pathway. Here, we discovered a pathogenic form of this surface protein, determined by a single tyrosine residue […]
Hristina Koceva, Mona Amiratashani, Parastoo Akbarimoghaddam, Bianca Hoffmann, Gaukhar Zhurgenbayeva, Mark S. Gresnigt, Vanessa Rossetto Marcelino, Christian Eggeling, Marc Thilo Figge, Maria-João Amorim and Alexander S. Mosig
The lung microbiome has recently gained attention for potentially affecting respiratory viral infections, including influenza A virus, respiratory syncytial virus (RSV) and SARS-CoV-2. We will discuss the complexities of the lung microenvironment in the context of viral infections and the use of organ-on-chip (OoC) models in replicating the respiratory tract milieu to aid in understanding […]
