Biology subjects

Kuhn, E. M. A.

Publications and source records attributed to Kuhn, E. M. A..

2 recordsLinked to original sources

bioRxiv2026

Beyond the skin barrier: commensal S. epidermidis imprint systemic immunity to invasive biofilm infection

Staphylococcus epidermidis, a dominant human skin commensal from early life, can transition to an opportunistic pathogen, including invasive, biofilm-associated infections linked to medical devices. Neonatal exposure to skin commensals induces a lifelong immunological imprint in the skin, characterized by immunoregulatory responses. We therefore hypothesized that early life exposure to S. epidermidis influences immune responses to invasive biofilm-associated infections later in life. Using a mouse model of biofilm-related S. epidermidis bone infection, we show that neonatal and adult skin colonization altered the immune response to the subsequent infection in adulthood. Neonatal colonization led to increased NK cells and neutrophils compared to no colonization, along with reduced Tregs and Th1 cells, and consistent increase in immune checkpoint receptor PD-1+ Tregs, T effector, Th1 and Th2 cells across infected bone marrow, blood and spleen. These PD-1-related immune modulations were absent in the adult-colonized group, which had the highest numbers of Tregs, Th1 and Th2 cells of all groups. These findings reveal that early exposure to commensal bacteria strongly impacts the response to invasive infection later in life. Notably, the response depends on the timing of previous exposure. Neonatal colonization drives T cell modulation, resembling neonatal immunity, while adult-colonization increases specific T cell abundance. These differences highlight the essential role of skin colonization in shaping the quality of pathogen immunity to protect against invasive, biofilm-associated infection later in life, emphasizing that immunological studies using uncolonized animal models may not fully capture human immune dynamics.

immunology↗

bioRxiv2025

TagF coordinates spike-loading as an intermediate checkpoint in Type VI Secretion System assembly

Diderm bacteria use contact-dependent Type VI secretion systems (T6SS) to gain a competitive advantage within bacterial communities and during infection. Whereas the structural core assembly of T6SS is well characterized, the role of diverse accessory proteins during assembly remains under investigation. One well-conserved accessory protein is TagF, a post-translational inhibitor of T6SS dynamics, which was previously characterized in the context of a kinase-phosphatase signaling relay. Here, we identify a subset of T6SS clusters in which TagF occurs in a distinct regulatory context and without known binding partners. Investigating the role of TagF in the constitutively active Acinetobacter baylyi T6SS, we show that though TagF can suppress assembly dynamics, it primarily acts as an assembly coordinator. Using structured illumination microscopy, we show that TagF coordinates the transition from baseplate assembly to sheath elongation by preventing premature and nonproductive sheath assembly in absence of the VgrG spike. Direct interactions with the conserved T6SS tube protein Hcp suggested that TagF blocks sheath elongation by binding and disrupting Hcp hexamers and thus preventing tube formation. Finally, we show that TagF activity depends on crosstalk with TagZ, a previously uncharacterized membrane-associated accessory protein that recruits TagF to the cell periphery, and demonstrate that this interaction can be specifically disrupted by expression of an artificial TagF-binding protein. Together, our findings establish a novel role of TagF as a checkpoint protein that controls for spike-insertion into the baseplate to ensure effective T6SS assembly.

microbiology↗