Biology subjects

Vollmuth, N.

Publications and source records attributed to Vollmuth, N..

4 recordsLinked to original sources

bioRxiv2026

Impact of Neurons on Group B Streptococcus Interactions at the Blood Brain Barrier

Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive opportunistic pathogen and the leading cause of neonatal bacterial meningitis, a life-threatening infection of the central nervous system (CNS) that occurs when bacteria cross the blood-brain barrier (BBB). GBS commonly colonizes the maternal genital tract and is a major cause of invasive neonatal disease, including bacteremia and meningitis. Despite treatment advances, GBS meningitis remains associated with substantial mortality and long-term neurological sequelae. The BBB is a highly specialized barrier formed by brain endothelial cells (BECs) that restrict microbial entry into the CNS through tightly regulated intercellular junctions. The BBB exists within the neurovascular unit, where neurons and other CNS cell types actively regulate endothelial barrier properties through intercellular signaling. However, the contribution of neuronal-endothelial interactions to BBB function during neonatal meningitis remains poorly understood. To investigate the mechanisms by which GBS disrupts and penetrates the BBB, we utilized induced pluripotent stem cell (iPSC)-derived brain-like endothelial cells. EZ-Sphere-derived neurons generated from the same iPSC source were incorporated into an isogenic BBB model to determine whether neuronal-endothelial communication influences GBS interaction with BECs. Neuronal co-culture significantly reduced GBS adherence to and invasion of BECs while preserving tight junction integrity during infection. Application of neuron-conditioned medium similarly decreased bacterial adherence and invasion, suggesting that neuron-derived soluble factors enhance barrier integrity during GBS infection. Together, these findings demonstrate that neuronal signaling enhances BBB resistance to GBS and highlight a previously underappreciated role for neurovascular crosstalk in limiting bacterial pathogenesis. ImportanceGroup B Streptococcus (GBS) is the leading cause of bacterial meningitis in newborns. GBS interacts with and crosses the blood-brain barrier (BBB) contributing to a potentially fatal infection without treatment. Understanding how the BBB interacts with bacterial pathogens is critical for developing new strategies to protect vulnerable infants. In this study, we used human stem cell-derived models to recapitulate the BBB and examine how communication between brain endothelial cells and neurons influence host response to bacterial infection. These findings identify neuronal-endothelial communication as a potential contributor to BBB protection and provide a foundation for future studies aimed at preventing GBS invasion of the central nervous system.

microbiology↗

bioRxiv2026

Chlamydia trachomatis infection upregulates MicroRNA21 to deplete tumor suppressor PTEN

Infection with obligate intracellular Chlamydia trachomatis (Ct) has been associated with cervical and ovarian carcinoma in humans. The possible cause of the tumor-promoting effect of the infection is thought to be a manipulation of host signaling pathways, which are essential for the growth of the bacteria, and which at the same time can support tumor growth. The PI3K and MAPK signaling cascades are outstanding candidates for this concept, as they are persistently activated during infection and required for the growth of Chlamydia and many tumors. The mechanism by which Chlamydia activates these pre-transforming survival signals in the cells is not well understood. Here we show that Ct infection up-regulates the oncomiR, miR21 by activating the host transcription factor AP-1. This depletes the target gene of miR-21, the tumor suppressor PTEN that ensures the persistent activation of the PI3K pathway. Blocking miR21 adversely affects the growth and development of the pathogen. We show here that miR21 KO mice are less susceptible to infection with Ct compared to control mice. Our data thus provides direct in vivo evidence of the induction and dependency of this obligate human pathogen on tumor-promoting miR-21-induced signaling. ImportanceChlamydia trachomatis is an obligate intracellular pathogen that relies on host metabolism for survival, yet the mechanisms by which it sustains nutrient access remain incompletely understood. Here, we identify a conserved host regulatory axis in which infection induces miR-21 to deplete the tumor suppressor PTEN, thereby enabling persistent activation of PI3K signaling. This pathway promotes a tumor-like metabolic state that supports bacterial growth while protecting infected cells from apoptosis. We further demonstrate that the AP-1-miR-21-PTEN circuit is required for efficient chlamydial replication in vitro and in vivo, and that disruption of miR-21 significantly impairs bacterial propagation in epithelial tissues. These findings reveal how C. trachomatis hijacks a central oncogenic signaling network to remodel host cell physiology and highlight a mechanistic link between infection and cancer-associated pathways. Targeting this host-driven signaling axis may provide new strategies for controlling infection independent of traditional antibiotics.

microbiology↗

bioRxiv2021

c-Myc plays a key role in IFN-γ induced persistence of Chlamydia trachomatis

Chlamydia trachomatis (Ctr) can persist over long periods of time within their host cell and thereby establish chronic infections. One of the major inducers of chlamydial persistence is interferon-gamma (IFN-{gamma}) released by immune cells as a mechanism of immune defence. IFN-{gamma} activates the catabolic depletion of L-tryptophan (Trp) via indoleamine 2,3-dioxygenase (IDO), resulting in persistent Chlamydia. Here we show that IFN-{gamma} depletes c-Myc, the key regulator of host cell metabolism, in a STAT1-dependent manner. Expression of c-Myc rescued Chlamydia from IFN-{gamma}-induced persistence in cultured cell lines, but also in human fallopian tube organoids. L-tryptophan concentrations control c-Myc levels via the PI3K-GSK3{beta} axis. Unbiased metabolic analysis revealed that Chlamydia infection reprograms the host cell tricarboxylic acid (TCA) cycle to support pyrimidine biosynthesis. Addition of TCA cycle intermediates or pyrimidine/purine nucleosides to infected cells rescued Chlamydia from IFN-{gamma}-induced persistence. Thus, our results challenge the longstanding hypothesis of L-tryptophan depletion through IDO as the major mechanism of IFN-{gamma}-induced metabolic immune defence and significantly extends the understanding of the role IFN-{gamma} as a broad modulator of host cell metabolism.

microbiology↗

bioRxiv2019

A central role of glutamine in Chlamydia infection

Obligate intracellular bacteria like Chlamydia trachomatis undergo a complex developmental cycle between infectious non-replicative (EBs) and non-infectious replicative (RBs) forms. EBs shortly after entering a host cell transform to RBs, a crucial process in infection, initiating chlamydial replication. As Chlamydia fail to replicate outside the host cell it is currently unknown how the transition from EBs to RBs is initiated. Here we show in a cell-free approach in axenic media that uptake of glutamine by the bacteria is critical to initiate EB-RB transition. These bacteria utilize glutamine to synthesize cell wall peptidoglycan which has recently been detected in the septa of replicating intracellular Chlamydia. The increased requirement for glutamine in infected cells is achieved by reprogramming the glutamine metabolism in a c-Myc-dependent manner. Glutamine was effectively taken up by the glutamine transporter SLC1A5 and metabolized via glutaminase. Interference with this metabolic reprogramming limited growth of Chlamydia. Intriguingly, Chlamydia failed to produce progeny in SLC1A5 knockout mice. Thus, we report on the central role of glutamine for the development of an obligate intracellular pathogenic bacterium and the reprogramming of host glutamine metabolism, which may provide a basis for innovative anti-infective strategies.

microbiology↗