Biology subjects

Hopp, M.-T.

Publications and source records attributed to Hopp, M.-T..

4 recordsLinked to original sources

bioRxiv2023

Oxidation of hemoglobin in the lung parenchyma facilitates the differentiation of pneumococci into encapsulated bacteria

Streptococcus pneumoniae (the pneumococcus) causes cytotoxicity and encapsulates within the lung parenchyma, leading to pneumococcal pneumonia. However, the underlying mechanisms remain unclear and likely involve multiple bacterial and host factors. We investigated the selection process of encapsulated pneumococci, a critical factor in lung damage during pneumococcal pneumonia. Our study revealed that pneumococci initially lack capsules but re-encapsulate upon reaching the alveoli. This process is driven by S. pneumoniae-derived hydrogen peroxide (Spn-H2O2), which oxidizes lung hemoglobin, leading to heme release and polymerized hemoglobin formation. Physiologically relevant levels of heme were found to promote the selection of encapsulated bacteria. Furthermore, encapsulation protects bacteria from intracellular heme toxicity, a defense absent in non-encapsulated strains. Ultrastructural analysis demonstrated interactions between hemoglobin and both encapsulated and non-encapsulated pneumococci in human sputum. These findings reveal a critical connection between oxidative stress-mediated lung damage and the selection of encapsulated pneumococci, suggesting potential therapeutic avenues by targeting these oxidative processes.

microbiology↗

bioRxiv2020

Unravelling the debate on heme effects in COVID-19 infections

The SARS-CoV-2 outbreak was recently declared a worldwide pandemic. Infection triggers the respiratory tract disease COVID-19, which is accompanied by serious changes of clinical biomarkers such as hemoglobin and interleukins. The same parameters are altered during hemolysis, which is characterized by an increase in labile heme. We present two approaches that aim at analyzing a potential link between available heme and COVID-19 pathogenesis. Four COVID-19 related proteins, i.e. the host cell proteins ACE2 and TMPRSS2 as well as the viral protein 7a and S protein, were identified as potential heme binders. We also performed a detailed analysis of the common pathways induced by heme and SARS-CoV-2 by superimposition of knowledge graphs covering heme biology and COVID-19 pathophysiology. Herein, focus was laid on inflammatory pathways, and distinct biomarkers as the linking elements. Finally, the results substantially improve our understanding of COVID-19 infections and disease progression of patients with different clinical backgrounds and expand the diagnostic and treatment options.

bioinformatics↗

bioRxiv2020

Revisiting the interaction of heme with hemopexin: Recommendations for the responsible use of an emerging drug

In hemolytic disorders, erythrocyte lysis results in massive release of hemoglobin and, subsequently, toxic heme. Hemopexin is the major protective factor against heme toxicity in human blood and currently considered for therapeutic use. It has been widely accepted that hemopexin binds heme with extraordinarily high affinity in a 1:1 ratio. Here we show that hemopexin binds heme with lower affinity than previously assumed and that the interaction ratio tends to 2:1 (heme:hemopexin) or above. The heme-binding sites of hemopexin were characterized using hemopexin-derived peptide models and competitive displacement assays. In addition, in silico molecular modelling with a newly created homology model of human hemopexin allowed us to propose a recruiting mechanism by which heme consecutively binds to several histidine residues and is finally funnelled into the high-affinity binding pocket. Our findings have direct implications for the biomedical application of hemopexin and its potential administration in hemolytic disorders.

biochemistry↗

bioRxiv2019

A computational approach for mapping heme biology in the context of hemolytic disorders

Heme is an iron ion-containing molecule found within hemoproteins such as hemoglobin and cytochromes that participates in diverse biological processes. While its unlimited supply has been implicated in deleterious processes in several diseases including malaria, sepsis, ischemia-reperfusion, and disseminated intravascular coagulation, little is known about its regulatory and signaling functions. A majority of the computational research to elucidate these functions has been purely data-driven due to the absence of curated pathway resources, which have proven useful in the computational study in other indications. Here, we present two resources aimed to exploit this unexplored information to model heme biology. The first resource is an ontology covering heme-specific terms not yet included in standard controlled vocabularies. Using this ontology, we curated and modeled a corpus of 46 scientific articles to generate a mechanistic knowledge graph representing the hemes interactome for that particular literature. Finally, we demonstrated the utility of these resources by investigating the role of heme in the Toll-like receptor signaling pathway. Our analysis proposed a series of crosstalk events that could explain the role of heme in activating the TLR4 signaling pathway. In summary, the presented work opens the door for the scientific community to explore in more detail the published knowledge on heme biology.

bioinformatics↗