TY  - JOUR
AB  - Aging is accompanied by considerable changes in the gut microbiome, yet the molecular mechanisms driving aging and the role of the microbiome remain unclear. Here we combined metagenomics, transcriptomics and metabolomics from aging mice with metabolic modelling to characterize host-microbiome interactions during aging. Reconstructing integrated metabolic models of host and 181 mouse gut microorganisms, we show a complex dependency of host metabolism on known and previously undescribed microbial interactions. We observed a pronounced reduction in metabolic activity within the aging microbiome accompanied by reduced beneficial interactions between bacterial species. These changes coincided with increased systemic inflammation and the downregulation of essential host pathways, particularly in nucleotide metabolism, predicted to rely on the microbiota and critical for preserving intestinal barrier function, cellular replication and homeostasis. Our results elucidate microbiome-host interactions that potentially influence host aging processes. These pathways could serve as future targets for the development of microbiome-based anti-aging therapies.
AU  - Best, L.*
AU  - Dost, T.*
AU  - Esser, D.*
AU  - Flor, S.*
AU  - Gamarra, A.M.*
AU  - Haase, M.*
AU  - Kadibalban, A.S.*
AU  - Marinos, G.*
AU  - Walker, A.
AU  - Zimmermann, J.*
AU  - Simon, R.*
AU  - Schmidt, S.*
AU  - Taubenheim, J.*
AU  - Künzel, S.*
AU  - Häsler, R.*
AU  - Franzenburg, S.*
AU  - Groth, M.*
AU  - Waschina, S.*
AU  - Rosenstiel, P.*
AU  - Sommer, F.*
AU  - Witte, O.W.*
AU  - Schmitt-Kopplin, P.
AU  - Baines, J.F.*
AU  - Frahm, C.*
AU  - Kaleta, C.*
C1  - 73783
C2  - 57219
CY  - Heidelberger Platz 3, Berlin, 14197, Germany
TI  - Metabolic modelling reveals the aging-associated decline of host-microbiome metabolic interactions in mice.
JO  - Nat. Microbiol.
PB  - Nature Portfolio
PY  - 2025
SN  - 2058-5276
ER  - 

TY  - JOUR
AB  - Varicella-zoster virus (VZV) infects most humans and causes chickenpox, shingles and central nervous system pathologies. The molecular basis for these phenotypes remains elusive. Here we conducted a multi-proteomic survey on 64 individual VZV proteins and infection-induced perturbations in a neuronal cell line, identifying 900 interactors and 3,618 regulated host proteins. Data integration suggested molecular functions of viral proteins, such as a mechanism for the ORF61-mediated IFI16 degradation via the recruitment of E3 ligase co-factors. Moreover, we identified proviral host factors (MPP8 and ZNF280D) as potential targets to limit infection. Integration of exome sequencing analysis from patients with VZV-associated central nervous system pathologies identified nephrocystin 4 as a viral restriction factor, and its S862N variant, which showed reduced activity and decreased binding to the regulatory proteins 14-3-3. Collectively, our study provides a comprehensive herpesvirus-host interface resource, which aids our understanding of disease-associated molecular perturbations and data-driven identification of antiviral treatment options.
AU  - Girault, V.*
AU  - Stukalov, A.*
AU  - Carter-Timofte, M.E.*
AU  - Hertzog, J.*
AU  - Verin, M.
AU  - Austen, K.*
AU  - Haas, D.A.*
AU  - Oubraham, L.*
AU  - Piras, A.*
AU  - Maidl, S.*
AU  - Öllinger, R.*
AU  - Rad, R.*
AU  - Protzer, U.*
AU  - Kaufer, B.B.*
AU  - Lebbink, R.J.*
AU  - Rehwinkel, J.*
AU  - Mogensen, T.H.*
AU  - Pichlmair, A.
C1  - 75275
C2  - 57887
CY  - Heidelberger Platz 3, Berlin, 14197, Germany
SP  - 2048-2072
TI  - Multi-proteomic profiling of the varicella-zoster virus-host interface reveals host susceptibilities to severe infection.
JO  - Nat. Microbiol.
VL  - 10
IS  - 8
PB  - Nature Portfolio
PY  - 2025
SN  - 2058-5276
ER  - 

TY  - JOUR
AB  - In the version of this article initially published online, in the header paragraph now starting “Contractile injection systems are nanomachines used by bacteria to puncture target cell membranes, thereby mediating bacterial competition and infection of eukaryotic cells,” bacterial competition was omitted. It has now been restored in the HTML and PDF versions of the article.
AU  - Righetto, R.D.*
AU  - Engel, B.D.*
C1  - 64584
C2  - 51887
TI  - Publisher Correction: Expanding the arsenal of bacterial spearguns (Nature Microbiology, (2022), 7, 3, (363-364), 10.1038/s41564-022-01078-z).
JO  - Nat. Microbiol.
PY  - 2022
SN  - 2058-5276
ER  - 

TY  - JOUR
AU  - Righetto, R.D.
AU  - Engel, B.D.
C1  - 64514
C2  - 51888
CY  - Heidelberger Platz 3, Berlin, 14197, Germany
SP  - 363-364
TI  - Expanding the arsenal of bacterial spearguns.
JO  - Nat. Microbiol.
VL  - 7
IS  - 3
PB  - Nature Portfolio
PY  - 2022
SN  - 2058-5276
ER  - 

TY  - JOUR
AB  - Viral discovery is accelerating at an unprecedented rate due to continuing advances in culture-independent sequence-based analyses. One important facet of this discovery is identification of the hosts of these recently characterized uncultured viruses. To this end, we have adapted the viral tagging approach, which bypasses the need for culture-based methods to identify host-phage pairings. Fluorescently labelled anonymous virions adsorb to unlabelled anonymous bacterial host cells, which are then individually sorted as host-phage pairs, followed by genome amplification and high-throughput sequencing to establish the identities of both the host and the attached virus(es). We demonstrate single-cell viral tagging using the faecal microbiome, including cross-tagging of viruses and bacteria between human subjects. A total of 363 unique host-phage pairings were predicted, most of which were subject-specific and involved previously uncharacterized viruses despite the majority of their bacterial hosts having known taxonomy. One-fifth of these pairs were confirmed by multiple individual tagged cells. Viruses targeting more than one bacterial species were conspicuously absent in the host-phage network, suggesting that phages are not major vectors of inter-species horizontal gene transfer in the human gut. A high level of cross-reactivity between phages and bacteria from different subjects was noted despite subject-specific viral profiles, which has implications for faecal micro-biota transplant therapy.
AU  - Džunková, M.*
AU  - Low, S.J.*
AU  - Daly, J.N.*
AU  - Deng, L.
AU  - Rinke, C.*
AU  - Hugenholtz, P.*
C1  - 56715
C2  - 47231
CY  - Macmillan Building, 4 Crinan St, London N1 9xw, England
SP  - 2192-2203
TI  - Defining the human gut host-phage network through single-cell viral tagging.
JO  - Nat. Microbiol.
VL  - 4
IS  - 12
PB  - Nature Publishing Group
PY  - 2019
SN  - 2058-5276
ER  - 

TY  - JOUR
AB  - Congenital Zika virus (ZIKV) syndrome may cause fetal microcephaly in -1% of affected newborns. Here, we investigate whether the majority of clinically inapparent newborns might suffer from long-term health impairments not readily visible at birth. Infection of immunocompetent pregnant mice with high-dose ZIKV caused severe offspring phenotypes, such as fetal death, as expected. By contrast, low-dose (LD) maternal ZIKV infection resulted in reduced fetal birth weight but no other obvious phenotypes. Male offspring born to LD ZIKV-infected mothers had increased testosterone (TST) levels and were less likely to survive in utero infection compared to their female littermates. Males also presented an increased number of immature neurons in apical and basal hippocampal dendrites, while female offspring had immature neurons in basal dendrites only. Moreover, male offspring with high but not very high (storm) TST levels were more likely to suffer from learning and memory impairments compared to females. Future studies are required to understand the impact of TST on neuropathological and neurocognitive impairments in later life. In summary, increased sex-specific vigilance is required in countries with high ZIKV prevalence, where impaired neurodevelopment may be camouflaged by a healthy appearance at birth.
AU  - Stanelle-Bertram, S.*
AU  - Walendy-Gnirß, K.*
AU  - Speiseder, T.*
AU  - Thiele, S.*
AU  - Asante, I.A.*
AU  - Dreier, C.*
AU  - Kouassi, N.M.*
AU  - Preuß, A.*
AU  - Pilnitz-Stolze, G.*
AU  - Müller, U.*
AU  - Thanisch, S.*
AU  - Richter, M.*
AU  - Scharrenberg, R.*
AU  - Kraus, V.*
AU  - Dörk, R.*
AU  - Schau, L.*
AU  - Herder, V.*
AU  - Gerhauser, I.*
AU  - Pfankuche, V.M.*
AU  - Käufer, C.*
AU  - Waltl, I.*
AU  - Moraes, T.*
AU  - Sellau, J.*
AU  - Hoenow, S.*
AU  - Schmidt-Chanasit, J.*
AU  - Jansen, S.*
AU  - Schattling, B.*
AU  - Ittrich, H.*
AU  - Bartsch, U.*
AU  - Renné, T.*
AU  - Bartenschlager, R.*
AU  - Arck, P.*
AU  - Cadar, D.*
AU  - Friese, M.A.*
AU  - Vapalahti, O.*
AU  - Lotter, H.*
AU  - Benites, S.*
AU  - Rolling, L.*
AU  - Gabriel, M.*
AU  - Baumgärtner, W.*
AU  - Morellini, F.*
AU  - Hölter, S.M.
AU  - Amarie, O.V.
AU  - Fuchs, H.
AU  - Hrabě de Angelis, M.
AU  - Löscher, W.*
AU  - Calderon de Anda, F.*
AU  - Gabriel, G.*
C1  - 54254
C2  - 45341
CY  - Macmillan Building, 4 Crinan St, London N1 9xw, England
SP  - 1161–1174
TI  - Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood.
JO  - Nat. Microbiol.
VL  - 3
IS  - 10
PB  - Nature Publishing Group
PY  - 2018
SN  - 2058-5276
ER  -