Abstract:
:Probiotics are living microorganisms that are increasingly used as gastrointestinal therapeutics by virtue of their innate or engineered genetic function. Unlike abiotic therapeutics, probiotics can replicate in their intended site, subjecting their genomes and therapeutic properties to natural selection. We exposed the candidate probiotic E. coli Nissle (EcN) to the mouse gastrointestinal tract over several weeks, systematically altering the diet and background microbiota complexity. In-transit EcN accumulates genetic mutations that modulate carbohydrate utilization, stress response, and adhesion to gain competitive fitness, while previous exposure to antibiotics reveals an acquisition of resistance. We then leveraged these insights to generate an EcN strain that shows therapeutic efficacy in a mouse model of phenylketonuria and found that it was genetically stable over 1 week, thereby validating EcN's utility as a chassis for engineering. Collectively, we demonstrate a generalizable pipeline that can be applied to other probiotics to better understand their safety and engineering potential.
journal_name
Cell Host Microbejournal_title
Cell host & microbeauthors
Crook N,Ferreiro A,Gasparrini AJ,Pesesky MW,Gibson MK,Wang B,Sun X,Condiotte Z,Dobrowolski S,Peterson D,Dantas Gdoi
10.1016/j.chom.2019.02.005subject
Has Abstractpub_date
2019-04-10 00:00:00pages
499-512.e8issue
4eissn
1931-3128issn
1934-6069pii
S1931-3128(19)30101-5journal_volume
25pub_type
杂志文章abstract::Characterization of single antibody lineages within infected individuals has provided insights into the development of Env-specific antibodies. However, a systems-level understanding of the humoral response against HIV-1 is limited. Here, we interrogated the antibody repertoires of multiple HIV-infected donors from an...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2018.05.001
更新日期:2018-06-13 00:00:00
abstract::Type III secretion systems (T3SS) are used by bacteria to deliver proteins into the cytoplasm of eukaryotic cells. Most studies of T3SS have focused on the role of these secretion systems in specific host interactions. However, there is increasing evidence to suggest that T3SS are also used in interactions with multip...
journal_title:Cell host & microbe
pub_type: 杂志文章,评审
doi:10.1016/j.chom.2007.10.004
更新日期:2007-11-15 00:00:00
abstract::(+)strand RNA viruses have to overcome various points of restriction in the host to establish successful infection. In plants, this includes RNA silencing. To uncover additional bottlenecks to RNA virus infection, we genetically attenuated the impact of RNA silencing on transgenically expressed Potato virus X (PVX), a...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2014.08.001
更新日期:2014-09-10 00:00:00
abstract::Herpes simplex virus 1 (HSV-1) establishes infections in humans and mice, but some non-human primates exhibit resistance via unknown mechanisms. Innate immune recognition pathways are highly conserved but are pivotal in determining susceptibility to DNA virus infections. We report that variation of a single amino acid...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2018.07.004
更新日期:2018-08-08 00:00:00
abstract::The human microbiome encodes extensive metabolic capabilities, but our understanding of the mechanisms linking gut microbes to human metabolism remains limited. Here, we focus on the conversion of cholesterol to the poorly absorbed sterol coprostanol by the gut microbiota to develop a framework for the identification ...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2020.05.013
更新日期:2020-08-12 00:00:00
abstract::Lujo virus (LUJV) is an arenavirus that emerged in 2008 associated with a cluster of human cases of severe hemorrhagic fever. In this issue of Cell Host & Microbe, Raaben et al. (2017) identify neuropilin (NRP)-2 as cell surface receptor and the tetraspannin protein CD63 as intracellular entry factor for LUJV. ...
journal_title:Cell host & microbe
pub_type: 评论,杂志文章
doi:10.1016/j.chom.2017.10.014
更新日期:2017-11-08 00:00:00
abstract::The presence of bacteria within epithelial-lined compartments, such as the lung, elicits rapid recruitment of innate immune cells. In this issue of Cell Host & Microbe, Chun and Prince (2009) report that epithelial cells facilitate this process by reorganizing their intercellular junctions to enhance immune cell trans...
journal_title:Cell host & microbe
pub_type: 评论,杂志文章
doi:10.1016/j.chom.2008.12.008
更新日期:2009-01-22 00:00:00
abstract::In this issue of Cell Host & Microbe, Thanabalasuriar et al. (2019) show how neutrophils and biofilm-forming bacteria respond reciprocally, resulting in the formation of a barricade comprised of neutrophil extracellular traps. Disrupting this exchange and the resulting barrier can be detrimental unless balanced in fav...
journal_title:Cell host & microbe
pub_type: 评论,杂志文章
doi:10.1016/j.chom.2019.03.014
更新日期:2019-04-10 00:00:00
abstract::The oral microbial community represents the best-characterized consortium associated with the human host. There are strong correlations between the qualitative composition of the oral microbiota and clinically healthy or diseased states. However, additional studies are needed to elucidate the mechanisms that define th...
journal_title:Cell host & microbe
pub_type: 杂志文章,评审
doi:10.1016/j.chom.2011.09.008
更新日期:2011-10-20 00:00:00
abstract::In response to virus infection, cells can alter protein expression to modify cellular functions and limit viral replication. To examine host protein expression during infection with human cytomegalovirus (HCMV), an enveloped DNA virus, we performed a semiquantitative, temporal analysis of the cell surface proteome in ...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2012.05.012
更新日期:2012-07-19 00:00:00
abstract::The intestinal microbiota is important for induction of inflammatory bowel disease (IBD). IBD is associated with complex shifts in microbiota composition, but it is unclear whether specific bacterial subsets induce IBD and, if so, whether their proportions in the microbiota are altered during disease. Here, we fulfill...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2011.04.009
更新日期:2011-05-19 00:00:00
abstract::Efforts to prevent human immunodeficiency virus type 1 (HIV-1) infection would benefit from understanding the factors that govern virus neutralization by antibodies. We present a mechanistic model for HIV-1 neutralization that includes both virus and antibody parameters. Variations in epitope integrity on the viral en...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2013.10.006
更新日期:2013-11-13 00:00:00
abstract::Influenza viruses are important pathogens which pose an ongoing threat to public health due to their ability to mutate and evade immunity elicited by prior infection or vaccination. Their evolutionary diversity is facilitated by the plasticity of the antigenically variable head domain of the major surface glycoprotein...
journal_title:Cell host & microbe
pub_type: 杂志文章,评审
doi:10.1016/j.chom.2018.06.016
更新日期:2018-07-11 00:00:00
abstract::Plant microbiome research highlights the importance of indigenous microbial communities for host phenotypes such as growth and health. It aims to discover the molecular basis by which host-microbe and microbe-microbe interactions shape and maintain microbial communities and to understand the role of individual microor...
journal_title:Cell host & microbe
pub_type: 杂志文章,评审
doi:10.1016/j.chom.2017.07.004
更新日期:2017-08-09 00:00:00
abstract::The Cullin-RING E3 ligase (CRL) family is commonly hijacked by pathogens to redirect the host ubiquitin proteasome machinery to specific targets. During HIV infection, CRL5 is hijacked by HIV Vif to target viral restriction factors of the APOBEC3 family for ubiquitination and degradation. Here, using a quantitative pr...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2019.05.008
更新日期:2019-07-10 00:00:00
abstract::Influenza A virus hemagglutinin (HA) initiates viral entry by engaging host receptor sialylated glycans via its receptor-binding site (RBS). The amino acid sequence of the RBS naturally varies across avian and human influenza virus subtypes and is also evolvable. However, functional sequence diversity in the RBS has n...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2017.05.011
更新日期:2017-06-14 00:00:00
abstract::HIV-1 can infect T cells by cell-free virus or by direct virion transfer between cells through cell contact-induced structures called virological synapses (VS). During VS-mediated infection, virions accumulate within target cell endosomes. We show that after crossing the VS, the transferred virus undergoes both matura...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2011.10.015
更新日期:2011-12-15 00:00:00
abstract::The innate and adaptive immune responses that confer resistance to the intracellular pathogen Toxoplasma gondii critically depend on IL-12 production, which drives interferon-γ (IFN-γ) expression. Certain cytokines can activate STAT3 and limit IL-12 production to prevent infection-associated immune pathology, but T. g...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2011.07.009
更新日期:2011-09-15 00:00:00
abstract::Monoclonal antibodies derived from blood plasma cells of acute HIV-1-infected individuals are predominantly targeted to the HIV Env gp41 and cross-reactive with commensal bacteria. To understand this phenomenon, we examined anti-HIV responses in ileum B cells using recombinant antibody technology and probed their rela...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2014.07.003
更新日期:2014-08-13 00:00:00
abstract::RNA interference (RNAi) is an established antiviral defense mechanism in plants and invertebrates. Whether RNAi serves a similar function in mammalian cells remains unresolved. We find that in some cell types, mammalian RNAi activity is reduced shortly after viral infection via poly-ADP-ribosylation of the RNA-induced...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2013.09.002
更新日期:2013-10-16 00:00:00
abstract::Viruses are involved in various interactions both within and between infected cells. Social evolution theory offers a conceptual framework for how virus-virus interactions, ranging from conflict to cooperation, have evolved. A critical examination of these interactions could expand our understanding of viruses and be ...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2017.09.012
更新日期:2017-10-11 00:00:00
abstract::Productive transcription of the HIV-1 genome involves RNA polymerase II working in concert with the viral protein Tat and its team of cofactors in a highly orchestrated process. Now, Pagans and colleagues report that the lysine methyltransferase Set7/9-KMT7 associates with Tat to stimulate RNA polymerase II elongation...
journal_title:Cell host & microbe
pub_type: 评论,杂志文章
doi:10.1016/j.chom.2010.03.001
更新日期:2010-03-18 00:00:00
abstract::Viruses have evolved a remarkable array of strategies to escape the host's innate immune responses. In this issue of Cell Host & Microbe, Zhao et al. (2016b) reveal a viral strategy to inactivate RIG-I signaling that relies on deamidation of RIG-I. ...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2016.11.011
更新日期:2016-12-14 00:00:00
abstract::Studying the microbial composition of internal organs and their associations with disease remains challenging due to the difficulty of acquiring clinical biopsies. We designed a statistical model to analyze the prevalence of species across sample types from The Cancer Genome Atlas (TCGA), revealing that species equipr...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2020.12.001
更新日期:2020-12-21 00:00:00
abstract::Pioneering plant research has shown that many Nod-like receptors (NLRs) detect pathogens indirectly via recognizing modifications of other host proteins. In this issue, two groups show that the RPM1 NLR is activated by phosphorylation of the host protein RIN4, probably resulting from activation of a host kinase by pat...
journal_title:Cell host & microbe
pub_type: 评论,杂志文章
doi:10.1016/j.chom.2011.02.002
更新日期:2011-02-17 00:00:00
abstract::In nonmyeloid cells, Shigella hijacks the mitochondrial checkpoint of cell death, thereby inducing a regulated form of necrosis depending on Bnip3 and cyclophilin D. Carneiro et al. (2009) describe the interplay between this program and a prosurvival response transmitted via the Nod1/Rip2/NF-kappaB/Bcl-2 axis, which d...
journal_title:Cell host & microbe
pub_type: 评论,杂志文章,评审
doi:10.1016/j.chom.2009.01.002
更新日期:2009-02-19 00:00:00
abstract::Autophagy is genetically associated with inflammatory bowel disease (IBD); however, its role remains unclear in disease pathogenesis. Three recent studies reveal a novel cytoprotective role of autophagy during viral, bacterial, and protozoan-triggered IBD (Burger et al., 2018; Matsuzawa-Ishimoto et al., 2017; Pott et ...
journal_title:Cell host & microbe
pub_type: 评论,杂志文章
doi:10.1016/j.chom.2018.01.015
更新日期:2018-02-14 00:00:00
abstract::Vancomycin-resistant Enterococcus (VRE) are highly antibiotic-resistant and readily transmissible pathogens that cause severe infections in hospitalized patients. We discovered that lithocholic acid (LCA), a secondary bile acid prevalent in the cecum and colon of mice and humans, impairs separation of growing VRE dipl...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2019.03.008
更新日期:2019-05-08 00:00:00
abstract::Variant surface antigens play an important role in Plasmodium falciparum malaria pathogenesis and in immune evasion by the parasite. Although most work to date has focused on P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1), two other multigene families encoding STEVOR and RIFIN are expressed in invasive merozoit...
journal_title:Cell host & microbe
pub_type: 杂志文章
doi:10.1016/j.chom.2014.06.004
更新日期:2014-07-09 00:00:00
abstract::Regulatory T cells (Tregs) are required to establish immune tolerance to commensal microbes. Tregs accumulate abruptly in the skin during a defined window of postnatal tissue development. However, the mechanisms mediating Treg migration to neonatal skin are unknown. Here we show that hair follicle (HF) development fac...
journal_title:Cell host & microbe
pub_type: 评论,杂志文章
doi:10.1016/j.chom.2017.03.001
更新日期:2017-04-12 00:00:00