Biology subjects

Steffen, P.

Publications and source records attributed to Steffen, P..

4 recordsLinked to original sources

bioRxiv2026

Immune variation and host ontogeny constrain pathogen virulence and transmission in a helminth parasite

Host immune strategies vary widely, yet how this variation shapes parasite virulence and transmission in natural systems remains unresolved. We tested whether host immune strategy governs macroparasite transmission timing and magnitude in Schistocephalus solidus, a cestode with a three-host life cycle. Over 13 months, we surveyed infection and immune activation (fibrosis) in second-intermediate host populations (threespine stickleback) from eight lakes. Host immune strategy (ranging from resistance to tolerance) strongly influenced whether and when parasites reached transmissible sizes, and shifted the synchrony between transmissible-stage peaks and definitive host availability. Across populations, transmission potential peaked at intermediate parasite burdens, consistent with virulence-transmission trade-off theory. These findings demonstrate that host immune phenotype alters epidemiological outcomes in complex life cycle parasites, by shifting both the magnitude and phenology of parasite growth to structure the effective transmission window.

ecology↗

bioRxiv2026

Constitutive and inducible fibrosis explain immune variation among threespine stickleback populations

Understanding how immune variation arises in natural populations requires disentangling the relative contributions of host genetic differences, environmental variation, and parasite effects, which is rarely possible in wild systems. Threespine stickleback populations vary in their use of intraperitoneal fibrosis as a defense against the helminth parasite Schistocephalus solidus, providing a natural system to study the genetic and ecological drivers of immune variation. We combined a 46-lake field survey with common garden experiments on 20 representative populations exposed to multiple parasite genotypes to test whether population differences in fibrosis persist under controlled conditions and whether they depend on parasite genotype or lake ecology. Fibrosis variation was strongly heritable, with both constitutive and inducible components persisting under common garden conditions. In contrast, parasite genotype had only a weak effect on fibrosis responses. Moreover, inducible fibrosis covaried with lake environmental conditions, with populations from more eutrophic-like lakes exhibiting stronger responses than those from more oligotrophic-like lakes. Together, these results reveal ecologically structured divergence in heritable immune responses among natural populations.

evolutionary biology↗

bioRxiv2022

Affinity-optimizing variants within the ZRS enhancer disrupt limb development

SummaryAn emerging regulatory principle governing enhancers is the use of suboptimal affinity binding sites to encode tissue-specific gene expression. Here we investigate if optimizing single-nucleotide variants that violate this principle can disrupt tissue-specific gene expression and development. The ZRS enhancer mediates expression of Shh in the posterior of the developing limb buds and is critical for limb and digit development. We find that the ZRS contains suboptimal-affinity ETS binding sites. Two human mutations and a synthetic mutation that optimize the affinity of the ETS-A site from 0.15 to 0.25 relative binding affinity cause polydactyly with the same penetrance and severity. Further increasing the affinity of the ETS-A site results in more penetrant and severe phenotypes. The prevalent use of suboptimal affinity binding sites within enhancers to encode tissue-specificity creates a vulnerability within genomes whereby variants that optimize affinity, even subtly, can be pathogenic. This provides a generalizable approach to identify causal variants that underlie enhanceropathies. In BriefSubtle increases in low-affinity sites underlie human limb defects, while greater increases in affinity lead to more severe and penetrant phenotypes. HighlightsPrediction and validation of pathogenic enhancer variants Very subtle increases in affinity of low-affinity sites are pathogenic Penetrance and severity of phenotype scales with increase in affinity

genetics↗

bioRxiv2019

Flagella methylation promotes bacterial adhesion and host cell invasion

The flagellum is the motility device of many bacteria and the long external filament is made of several thousand copies of a single protein, flagellin. While posttranslational modifications of flagellin are common among bacterial pathogens, the role of lysine methylation remained unknown. Here, we show that both flagellins of Salmonella enterica, FliC and FljB, are methylated at surface-exposed lysine residues. A Salmonella mutant deficient in flagellin methylation was outcompeted for gut colonization in a gastroenteritis mouse model. In support, methylation of flagellin promoted invasion of epithelial cells in vitro. Lysine methylation increased the surface hydrophobicity of flagellin and enhanced flagella-dependent adhesion of Salmonella to phosphatidylcholine vesicles and epithelial cells. In summary, posttranslational flagellin methylation constitutes a novel mechanism how flagellated bacteria facilitate adhesion to hydrophobic host cell surfaces and thereby contributes to efficient gut colonization and successful infection of the host.

microbiology↗