Biology subjects

Gallagher, K. A.

Publications and source records attributed to Gallagher, K. A..

4 recordsLinked to original sources

bioRxiv2026

Regulatory divergence and functional diversification of a c-di-GMP-controlled sigma factor in Actinomycetota

Members of the {sigma}28 family of alternative {sigma} factors typically regulate genes involved in flagellar biosynthesis. However, the only member of the {sigma}28 family present in the actinobacterial genus Streptomyces, WhiG, controls the differentiation of aerial hyphae into spores. WhiG activity is regulated by the second messenger c-di-GMP, which arms its cognate anti-{sigma}, RsiG, to bind and sequester the {sigma} factor. Understanding WhiG evolution can thus shed light on the diversity of processes regulated by c-di-GMP across Phylum Actinomycetota. Members of Actinomycetota comprise highly diverse filamentous and unicellular, flagellated and non-flagellated species, and the actinobacterial ancestor is predicted to have been motile. Here, our systematic analysis reveals that WhiG homologs are broadly distributed throughout the Actinomycetota and form two distinct clades: WhiG1, whose members have retained the ancestral association with the flagellar biosynthesis cluster and are not regulated by an RsiG anti-{sigma}, and WhiG2, whose members are typically regulated by RsiG via c-di-GMP. Bioinformatic analysis of their target regulons suggests that this {sigma} factor has significantly diversified in function to control various processes, including motility, chemotaxis, Type IV pili synthesis, sporulation, antibiotic biosynthesis, and c-di-GMP metabolism across diverse actinobacterial species. These findings highlight a phylogenetic split in the regulation and function of this key transcription factor throughout the phylum. ImportanceMounting global responses to dynamic environmental conditions is a crucial function that bacterial cells must perform. Global regulatory networks are most often studied in individual species, however, understanding how regulatory networks have evolved in distinct bacterial lineages remains an outstanding question. The alternative factor WhiG, which is found in the actinobacterial genus Streptomyces, is a dedicated sporulation , yet has long been known to have a close evolutionary relationship to factors that are responsible for regulation of flagellar biosynthesis. Analysis of the distribution of WhiG in Phylum Actinomycetota reveals that homologs typically co-occur with either a flagellar cluster or the c-di-GMP-binding anti- RsiG. Functional predictions of WhiG target genes across the Actinomycetota further reveal that diverse biological processes are controlled by these transcription factors, most notably motility, chemotaxis, Type IV pili biosynthesis, regulation of gene expression, c-di-GMP metabolism, and specialized metabolite biosynthesis.

microbiology↗

bioRxiv2025

VGLL3-centered network connects placental, vascular, and immune defects in preeclampsia

Preeclampsia affects approximately 1 in 10 pregnancies, leading to severe complications and long-term health risks for both mother and offspring. While the etiology remains unclear, preeclampsia has been linked to both autoimmunity and the timing of menarche. Through human single-cell and spatial analyses, coupled with in vitro, in vivo, and ex vivo models, we demonstrate that VGLL3, a transcription co-regulator in the Hippo pathway, is upregulated in preeclamptic placentas. VGLL3 promotes immune activation, impairs trophoblast differentiation, and induces endothelial dysfunction, all of which contribute to pregnancy-related hypertension, fetal growth restriction, and offspring mortality. Our data reveal that VGLL3 acts upstream of preeclampsia-associated processes, including the production of sFLT1, a key biomarker of the disease. Notably, targeting VGLL3--either by genetic deletion in mouse placentas or through therapeutic inhibition in human placentas--protects against preeclampsia and alleviates disease pathology. These findings position VGLL3 as a promising novel therapeutic target for preeclampsia.

immunology↗

bioRxiv2024

Phenotypic plasticity in bacterial elongation among closely related species

Cell elongation is a fundamental component of the bacterial cell cycle and has been studied over many decades, in part owing to its mechanisms being a target of numerous antibiotic classes. While several distinct modes of cell elongation have been described, these studies have largely relied on a handful of model bacterial species. Therefore, we have a limited view of the diversity of cell elongation approaches that are employed by bacteria, and how these vary in response to evolutionary and environmental influences. Here, by employing fluorescent D-amino acids (FDAAs) to track the spatiotemporal dynamics of elongation, we reveal previously unsuspected diversity of elongation modes among closely related species of the Caulobacteraceae, with species-specific combinations of dispersed, midcell and polar elongation that can be either unidirectional or bidirectional. Using genetic, cell biology, and phylogenetic approaches, we demonstrate that evolution of unidirectional-midcell elongation is accompanied by changes in the localization pattern of the peptidoglycan synthase PBP2 and infer that elongation complexes display a high degree of phenotypic plasticity, both among the Caulobacteraceae and more widely among the Alphaproteobacteria. Demonstration that even closely related bacterial species employ highly distinct mechanisms of cell elongation reshapes our understanding of the evolution and regulation of bacterial cell growth, with broad implications for bacterial morphology, adaptation, and antibiotic resistance.

microbiology↗

bioRxiv2021

Multicellular growth and sporulation in filamentous actinobacteria require the conserved cell division protein SepX

Filamentous actinobacteria such as Streptomyces undergo two distinct modes of cell division, leading to partitioning of growing hyphae into multicellular compartments via cross-walls, and to septation and release of unicellular spores. Specific determinants for cross-wall formation and the importance of hyphal compartmentalization for Streptomyces development are largely unknown. Here we show that SepX, an actinobacterial-specific protein, is crucial for both cell division modes in Streptomyces venezuelae. Importantly, we find that sepX-deficient mutants grow without cross-walls and that this substantially impairs the fitness of colonies and the coordinated progression through the developmental life cycle. Protein interaction studies and live-cell imaging suggest that SepX contributes to the stabilization of the divisome, a mechanism that also requires the dynamin-like protein DynB. Thus, our work identifies an important determinant for cell division in Streptomyces that is required for cellular development and sporulation.

microbiology↗