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PLOS Biology: New Articles

  • The details and entropy demons in a transmembrane allosteric machine

    by Ben F. Luisi

    In the model gram-negative bacterium Escherichia coli, three of the four Type VII ATP-binding cassette (ABC) transporter systems have been well characterized structurally and functionally. A new study reports the cryo-EM structures of the fourth Type VII ABC system, YbbAP-TesA, and provides evidence for its role in extracting hydrophobic compounds from the bacterial inner membrane and their subsequent hydrolytic transformation. In E.coli, three of the four Type VII ABC transporter systems have been structurally characterized. This Primer explores a recent study in PLOS Biology that reports the cryo-EM structures of the fourth Type VII system, YbbAP-TesA, and suggests that YbbAP has a role in extracting hydrophobic compounds from the bacterial inner membrane.

  • The host range of generalist and specialist phages in capsule-diverse <i>Klebsiella</i> hosts is driven by the evolvability of receptor-binding proteins

    by Celia Ferriol-González, Pilar Domingo-Calap

    Capsule diversity is a major limiting factor for phage host range in capsulated bacterial hosts. Phage receptor-binding proteins (RBPs) recognize the capsule and initiate infection, making them key players in phage tropism. In this study, we applied an experimental evolution approach to investigate host range adaptation in a diverse 12-phage community interacting with a Klebsiella spp. community containing 39 distinct capsular types. Our findings revealed that generalist phages possessed highly evolvable RBPs, accumulating non-synonymous mutations that modulated their host range. In contrast, specialist phages acquired fewer mutations but remained stable in the community, maintaining their narrow host range. Additionally, recombination between co-infecting closely related phages facilitated rapid host range adaptation through RBP swapping. However, most recombined genes encoded endonucleases or proteins of unknown function, suggesting their potential role in phage survival. This study advances our understanding of phage host range evolution and provides new insights for optimizing phage-based applications.

  • Large-scale seroepidemiology uncovers nephro-urological pathologies in people with tau autoimmunity

    by Andreia D. Magalhães, Marc Emmenegger, Elena De Cecco, Manfredi Carta, Karl Frontzek, Andra Chincisan, Jingjing Guo, Simone Hornemann, Adriano Aguzzi

    Intraneuronal aggregates of the microtubule-associated protein tau play a pivotal role in Alzheimer’s disease and several other neurodegenerative syndromes. Anti-tau antibodies can reduce pathology in mouse models of neurodegeneration and are currently being tested in humans. Here, we performed a large-scale seroepidemiological search for anti-tau IgG autoantibodies (ατ) on 40,497 human plasma samples. High-titer ατ+ individuals were surprisingly prevalent, with hospital patients being three times more likely to be ατ+ (EC50 ≥ 26; a nominal dilution of >1/64) than healthy blood donors (4.8% versus 1.6%). The prevalence increased with age over 70 years-old (RR 1.26, 95% CI 1.11–1.43, P < 0.001) and was higher for women (RR 1.20, 95% CI 1.07–1.39, P = 0.002). The autoantibodies bound selectively to tau, inhibited tau aggregation in vitro, and interfered with tau detection in plasma samples. No association was found between ατ autoantibodies and neurological disorders. Instead, tau autoreactivity showed a significant association with kidney and urinary disorders (adjusted RR 1.27, 95% CI 1.10–1.45, P = 0.001 and 1.40, 95% CI 1.20–1.63, P < 0.001, respectively). These results suggest a previously unrecognized association between ατ autoimmunity and extraneural diseases.

  • Electrical Spinal Imaging: A noninvasive, high-resolution approach that enables electrophysiological mapping of the human spinal cord

    by Giulio Gabrieli, Richard Somervail, André Mouraux, Massimo Leandri, Patrick Haggard, Gian Domenico Iannetti

    The spinal cord is the key bridge between the brain and the body. However, scientific understanding of healthy spinal cord function has historically been limited because noninvasive measures of its neural activity have proven exceptionally challenging. In this work, we describe an enhanced recording and analysis approach, Electrical Spinal Imaging (ESI), to obtain noninvasive, high-resolution images of the spinal cord electrical activity in humans. ESI is analytically simple, easy to implement, and data-driven: it does not involve template-based strategies prone to produce spurious signals. Using this approach, we provide a detailed description and physiological characterization of the spatiotemporal dynamics of the peripheral, spinal, and cortical activity elicited by somatosensory stimulation. We also demonstrate that attention modulates postsynaptic activity at spinal cord level. Our method has enabled five important insights regarding spinal cord activity. (1) We identified three distinct responses in the time domain: sP9, sN13, and sP22. (2) The sP9 is a traveling wave reflecting the afferent volley entering the spinal cord through the dorsal root. (3) In contrast, the sN13 and sP22 reflect segmental postsynaptic activity. (4) While the sP9 response is first seen on the dorsal electrodes ipsilateral to the stimulated side, the sN13 and sP22 were not lateralized with respect to the side of stimulation. (5) Unimodal attention strongly modulates the amplitude of the sP22, but not that of the sP9 and sN13 components. The proposed method offers critical insights into the spatiotemporal dynamics of somatosensory processing within the spinal cord, paving the way for precise noninvasive functional monitoring of the spinal cord in basic and clinical neurophysiology.

  • Enrichment of root-associated &lt;i&gt;Streptomyces&lt;/i&gt; strains in response to drought is driven by diverse functional traits and does not predict beneficial effects on plant growth

    by Citlali Fonseca-Garcia, Dean Pettinga, Daniel Caddell, Hannah Ploemacher, Katherine Louie, Benjamin P. Bowen, Joelle Park, Jesus Sanchez, Alen Zimic-Sheen, Matthew F. Traxler, Trent R. Northen, Devin Coleman-Derr

    The genus Streptomyces has consistently been found enriched in drought-stressed plant root microbiomes, yet the ecological basis and functional variation underlying this enrichment at the strain and isolate level remain unclear. Using two 16S rRNA sequencing methods with different levels of taxonomic resolution, we confirmed drought-associated enrichment (DE) of Streptomyces in field-grown sorghum roots and identified five closely related but distinct amplicon sequence variants (ASVs) belonging to the genus with variable drought enrichment patterns. From a culture collection of sorghum root endophytes, we selected 12 Streptomyces isolates representing these ASVs for phenotypic and genomic characterization. Whole-genome sequencing revealed substantial variation in gene content, even among closely related isolates, and exometabolomic profiling showed distinct metabolic responses to media supplemented with drought- versus well-watered root tissue. Traits linked to drought survival, including osmotic stress tolerance, siderophore production, and carbon utilization, varied widely among isolates and were not phylogenetically conserved. Using a broader panel of 48 Streptomyces, we demonstrate that DE scores, determined through mono-association experiments in gnotobiotic sorghum systems, showed high variability and lacked correlation with plant growth promotion. Pangenome-wide association identified orthogroups involved in osmolyte transport (e.g., proP) and membrane biosynthesis (e.g., fabG) as positively associated with DE, though most associations lacked phylogenetic signal. Collectively, these results demonstrate that Streptomyces DE is not a conserved genus-level trait but is instead strain-specific and functionally heterogeneous. Furthermore, DE in the root microbiome was shown not to predict beneficial effects on plant growth. This work underscores the need to resolve functional traits at the strain level and highlights the complexity of microbe-host-environment interactions under abiotic stress.