Amy Jacobson

All Publications

• Mammalian Lipopolysaccharide Receptors Incorporated into the Retroviral Envelope Augment Virus Transmission CELL HOST & MICROBE Wilks, J., Lien, E., Jacobson, A. N., Fischbach, M. A., Qureshi, N., Chervonsky, A. V., Golovkina, T. V. 2015; 18 (4): 456-462

  Abstract

  The orally transmitted retrovirus mouse mammary tumor virus (MMTV) requires the intestinal microbiota for persistence. Virion-associated lipopolysaccharide (LPS) activates Toll-like receptor 4 (TLR4), stimulating production of the immunosuppressive cytokine IL-10 and MMTV evasion of host immunity. However, the mechanisms by which MMTV associates with LPS remain unknown. We find that the viral envelope contains the mammalian LPS-binding factors CD14, TLR4, and MD-2, which, in conjunction with LPS-binding protein (LBP), bind LPS to the virus and augment transmission. MMTV isolated from infected mice lacking these LBPs cannot engage LPS or stimulate TLR4 and have a transmission defect. Furthermore, MMTV incorporation of a weak agonist LPS from Bacteroides, a prevalent LPS source in the gut, significantly enhances the ability of this LPS to stimulate TLR4, suggesting that MMTV intensifies these immunostimulatory properties. Thus, an orally transmitted retrovirus can capture, modify, and exploit mammalian receptors for bacterial ligands to ensure successful transmission.

  View details for DOI 10.1016/j.chom.2015.09.005

  View details for Web of Science ID 000365111600013

  View details for PubMedID 26468748

  View details for PubMedCentralID PMC4795803

• A Phase-Variable Surface Layer from the Gut Symbiont Bacteroides thetaiotaomicron MBIO Taketani, M., Donia, M. S., Jacobson, A. N., Lambris, J. D., Fischbach, M. A. 2015; 6 (5)

  Abstract

  The capsule from Bacteroides, a common gut symbiont, has long been a model system for studying the molecular mechanisms of host-symbiont interactions. The Bacteroides capsule is thought to consist of an array of phase-variable polysaccharides that give rise to subpopulations with distinct cell surface structures. Here, we report the serendipitous discovery of a previously unknown surface structure in Bacteroides thetaiotaomicron: a surface layer composed of a protein of unknown function, BT1927. BT1927, which is expressed in a phase-variable manner by ~1:1,000 cells in a wild-type culture, forms a hexagonally tessellated surface layer. The BT1927-expressing subpopulation is profoundly resistant to complement-mediated killing, due in part to the BT1927-mediated blockade of C3b deposition. Our results show that the Bacteroides surface structure is capable of a far greater degree of structural variation than previously known, and they suggest that structural variation within a Bacteroides species is important for productive gut colonization.Many bacterial species elaborate a capsule, a structure that resides outside the cell wall and mediates microbe-microbe and microbe-host interactions. Species of Bacteroides, the most abundant genus in the human gut, produce a capsule that consists of an array of polysaccharides, some of which are known to mediate interactions with the host immune system. Here, we report the discovery of a previously unknown surface structure in Bacteroides thetaiotaomicron. We show that this protein-based structure is expressed by a subset of cells in a population and protects Bacteroides from killing by complement, a component of the innate immune system. This novel surface layer protein is conserved across many species of the genus Bacteroides, suggesting an important role in colonization and host immune modulation.

  View details for DOI 10.1128/mBio.01339-15

  View details for Web of Science ID 000364523100038

  View details for PubMedID 26419879

  View details for PubMedCentralID PMC4611039

• Congo Red Interactions with Curli-Producing E. coli and Native Curli Amyloid Fibers. PloS one Reichhardt, C., Jacobson, A. N., Maher, M. C., Uang, J., McCrate, O. A., Eckart, M., Cegelski, L. 2015; 10 (10)

  View details for DOI 10.1371/journal.pone.0140388

  View details for PubMedID 26485271