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1.
Nat Chem Biol ; 20(2): 201-210, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38012344

RESUMO

Bacteria can be programmed to create engineered living materials (ELMs) with self-healing and evolvable functionalities. However, further development of ELMs is greatly hampered by the lack of engineerable nonpathogenic chassis and corresponding programmable endogenous biopolymers. Here, we describe a technological workflow for facilitating ELMs design by rationally integrating bioinformatics, structural biology and synthetic biology technologies. We first develop bioinformatics software, termed Bacteria Biopolymer Sniffer (BBSniffer), that allows fast mining of biopolymers and biopolymer-producing bacteria of interest. As a proof-of-principle study, using existing pathogenic pilus as input, we identify the covalently linked pili (CLP) biosynthetic gene cluster in the industrial workhorse Corynebacterium glutamicum. Genetic manipulation and structural characterization reveal the molecular mechanism of the CLP assembly, ultimately enabling a type of programmable pili for ELM design. Finally, engineering of the CLP-enabled living materials transforms cellulosic biomass into lycopene by coupling the extracellular and intracellular bioconversion ability.


Assuntos
Bactérias , Engenharia Metabólica , Fluxo de Trabalho , Licopeno , Biopolímeros
2.
BMC Biol ; 19(1): 131, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172070

RESUMO

BACKGROUND: Plant pathogens and their hosts undergo adaptive changes in managed agricultural ecosystems, by overcoming host resistance, but the underlying genetic adaptations are difficult to determine in natural settings. Verticillium dahliae is a fungal pathogen that causes Verticillium wilt on many economically important crops including lettuce. We assessed the dynamics of changes in the V. dahliae genome under selection in a long-term field experiment. RESULTS: In this study, a field was fumigated before the Verticillium dahliae race 1 strain (VdLs.16) was introduced. A derivative 145-strain population was collected over a 6-year period from this field in which a seggregating population of lettuce derived from Vr1/vr1 parents were evaluated. We de novo sequenced the parental genome of VdLs.16 strain and resequenced the derivative strains to analyze the genetic variations that accumulate over time in the field cropped with lettuce. Population genomics analyses identified 2769 single-nucleotide polymorphisms (SNPs) and 750 insertion/deletions (In-Dels) in the 145 isolates compared with the parental genome. Sequence divergence was identified in the coding sequence regions of 378 genes and in the putative promoter regions of 604 genes. Five-hundred and nine SNPs/In-Dels were identified as fixed. The SNPs and In-Dels were significantly enriched in the transposon-rich, gene-sparse regions, and in those genes with functional roles in signaling and transcriptional regulation. CONCLUSIONS: Under the managed ecosystem continuously cropped to lettuce, the local adaptation of V. dahliae evolves at a whole genome scale to accumulate SNPs/In-Dels nonrandomly in hypervariable regions that encode components of signal transduction and transcriptional regulation.


Assuntos
Ascomicetos , Ecossistema , Lactuca/genética , Doenças das Plantas/genética
3.
Mol Plant Microbe Interact ; 33(11): 1265-1269, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32967552

RESUMO

Verticillium dahliae is a widespread fungal pathogen that causes Verticillium wilt on many economically important crops and ornamentals worldwide. Populations of V. dahliae have been divided into two distinct races based upon differential host responses in tomato and lettuce. Recently, the contemporary race 2 isolates were further divided into an additional race in tomato. Herein, we provide a high-quality reference genome for the race 1 strain VdLs.16 isolated from lettuce in California, U.S.A. This resource will contribute to ongoing research that aims to elucidate the genetic basis of V. dahliae pathogenicity and population genomic diversity.


Assuntos
Genoma Fúngico , Lactuca/microbiologia , Doenças das Plantas/microbiologia , Verticillium , Verticillium/genética , Virulência
4.
Microbiol Spectr ; 12(4): e0115423, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38441468

RESUMO

Previous studies have profiled the gut microbiota among psoriatic patients compared to that among healthy individuals. However, a comprehensive understanding of the magnitude, direction, and detailed compositional and functional profiles remains limited. Additionally, research exploring the gut microbiota in the context of both plaque psoriasis (PsO) and psoriatic arthritis (PsA) is lacking. To assess the taxonomic and functional characteristics of the gut microbiota in PsO and PsA patients and investigate potential links between the gut microbiota and disease pathogenesis. We collected fecal samples from 70 psoriatic patients (44 PsO and 26 PsA) and 25 age- and gender-matched healthy controls (HC) and employed deep metagenomic sequencing to characterize their gut microbiota. We noted significant alternations in the gut microbiota compositions of both PsO and PsA patients compared to those of HC. Despite limited effect sizes in alpha diversity (12.3% reduction of microbial richness but unchanged evenness in psoriatic patients) and beta diversity (disease accounts for 3.5% of total variations), we consistently observed substantial reductions of Eubacterium rectale in both PsO and PsA patients, with PsA patients exhibiting even lower levels of E. rectale than PsO patients. Additionally, two Alistipes species were also depleted in psoriatic patients. These microorganisms are known to play crucial roles in carbohydrate metabolism pathways, mainly producing short-chain fatty acids with anti-inflammatory effects. Overall, our observations supplemented the profiling of altered gut microbiota in patients with PsO and PsA at the species level and described a link between the dominant short-chain fatty acid-producing bacterial species and systemic immunity in psoriatic patients. IMPORTANCE: In this observational clinical study with sufficient sample size and metagenomic sequencing to profile the gut microbiota, we identified consistent signals of the depleted abundance of Eubacterium rectale and related functional genes among psoriatic patients, including those with psoriatic arthritis. E. rectale may serve as an ecologically important functional unit in the gut microbiota, holding potential as a diagnostic marker and target for therapeutic interventions to achieve lasting effects. Our findings provide comprehensive gut microbiota profiling in psoriasis, resolving previous contradictions and generating new hypotheses for further investigation. These insights may significantly impact psoriasis management and related conditions.


Assuntos
Artrite Psoriásica , Microbioma Gastrointestinal , Psoríase , Humanos , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/metabolismo , Eubacterium , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Psoríase/metabolismo , Fezes
5.
Sci Rep ; 13(1): 9988, 2023 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-37340081

RESUMO

Metabolic associated fatty liver disease (MAFLD) is rising in incidence and is an increasingly common cause of cirrhosis and hepatocellular carcinoma (HCC). Alterations in the gut microbiota have been shown to correlate with the development and progression of MAFLD. However, little is known regarding differences in the gut microbiomes of MAFLD patients and healthy cohorts, and subgroups at the abnormal activity of hepatic enzymes in China. In this study, we enrolled 81 MAFLD patients and 25 healthy volunteers. The fecal microbiota was assessed using 16S rRNA gene sequencing and metagenomic sequencing. The results suggested that Ruminococcus obeum and Alistipes were most enriched in healthy individuals when compared with MAFLD patients. Microbe-set Enrichment Analysis (MSEA) results showed Dorea, Lactobacillus and Megasphaera are enriched in MAFLD group. We also found that Alistipes has negatively related to serum glucose (GLU), gamma-glutamyl transferase (GGT), and alanine aminotransferase (ALT). Moreover, the abundance of Dorea was found to be significantly overrepresented in the MAFLD patients and the degree of enrichment increased with the increasing abnormal liver enzyme. An increase in Dorea, combined with decreases in Alistipes appears to be characteristic of MAFLD patients. Further study of microbiota may provide a novel insight into the pathogenesis of MAFLD as well as a novel treatment strategy.


Assuntos
Carcinoma Hepatocelular , Microbioma Gastrointestinal , Neoplasias Hepáticas , Microbiota , Hepatopatia Gordurosa não Alcoólica , Humanos , RNA Ribossômico 16S/genética , Bacteroidetes , Clostridiaceae
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