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1.
Curr Opin Virol ; 51: 207-215, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34781105

RESUMO

Historically, virus taxonomy has been limited to describing viruses that were readily cultivated in the laboratory or emerging in natural biomes. Metagenomic analyses, single-particle sequencing, and database mining efforts have yielded new sequence data on an astounding number of previously unknown viruses. As metagenomes are relatively free of biases, these data provide an unprecedented insight into the vastness of the virosphere, but to properly value the extent of this diversity it is critical that the viruses are taxonomically classified. Inclusion of uncultivated viruses has already improved the process as well as the understanding of the taxa, viruses, and their evolutionary relationships. The continuous development and testing of computational tools will be required to maintain a dynamic virus taxonomy that can accommodate the new discoveries.

2.
EBioMedicine ; 74: 103649, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34814051

RESUMO

BACKGROUND: Shotgun metagenomics has been used clinically for diagnosing infectious diseases. However, most technical assessments have been limited to individual sets of reference standards, experimental workflows, and laboratories. METHODS: A reference panel and performance metrics were designed and used to examine the performance of shotgun metagenomics at 17 laboratories in a coordinated collaborative study. We comprehensively assessed the reliability, key performance determinants, reproducibility, and quantitative potential. FINDINGS: Assay performance varied significantly across sites and microbial classes, with a read depth of 20 millions as a generally cost-efficient assay setting. Results of mapped reads by shotgun metagenomics could indicate relative and intra-site (but not absolute or inter-site) microbial abundance. INTERPRETATION: Assay performance was significantly impacted by the microbial type, the host context, and read depth, which emphasizes the importance of these factors when designing reference reagents and benchmarking studies. Across sites, workflows and platforms, false positive reporting and considerable site/library effects were common challenges to the assay's accuracy and quantifiability. Our study also suggested that laboratory-developed shotgun metagenomics tests for pathogen detection should aim to detect microbes at 500 CFU/mL (or copies/mL) in a clinically relevant host context (10^5 human cells/mL) within a 24h turn-around time, and with an efficient read depth of 20M. FUNDING: This work was supported by National Science and Technology Major Project of China (2018ZX10102001).

3.
China CDC Wkly ; 3(38): 793-798, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34594992

RESUMO

What is already known on this topic?: Human adenovirus (HAdV) was frequently associated with acute respiratory disease (ARD) outbreaks in military camps. What is added by this report?: HAdV-B7, HAdV-B14, and HAdV-B55 were determined to be responsible for 3, 2, and 4 ARD outbreaks in military camps, China, respectively, with a total attack rate of 28.0% during 2011 to 2014. What are the implications for public health practice?: The findings suggest that vaccine development and administration in military camps must be prioritized. Quarantining among new recruits before entering into the military and the identification of the major responsible genotypes at the current stage is warranted.

5.
Front Bioeng Biotechnol ; 9: 741364, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631682

RESUMO

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a growing family of natural products that exhibit a range of structures and bioactivities. Initially assembled from the twenty proteinogenic amino acids in a ribosome-dependent manner, RiPPs assume their peculiar bioactive structures through various post-translational modifications. The essential modifications representative of each subfamily of RiPP are performed on a precursor peptide by the so-called processing enzymes; however, various tailoring enzymes can also embellish the precursor peptide or processed peptide with additional functional groups. Lasso peptides are an interesting subfamily of RiPPs characterized by their unique lariat knot-like structure, wherein the C-terminal tail is inserted through a macrolactam ring fused by an isopeptide bond between the N-terminal amino group and an acidic side chain. Until recently, relatively few lasso peptides were found to be tailored with extra functional groups. Nevertheless, the development of new routes to diversify lasso peptides and thus introduce novel or enhanced biological, medicinally relevant, or catalytic properties is appealing. In this review, we highlight several strategies through which lasso peptides have been successfully modified and provide a brief overview of the latest findings on the tailoring of these peptides. We also propose future directions for lasso peptide tailoring as well as potential applications for these peptides in hybrid catalyst design.

6.
Front Cell Infect Microbiol ; 11: 680127, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527599

RESUMO

Since the first reported case caused by the novel coronavirus SARS-CoV-2 infection in Wuhan, COVID-19 has caused serious deaths and an ongoing global pandemic, and it is still raging in more than 200 countries and regions around the world and many new variants have appeared in the process of continuous transmission. In the early stage of the epidemic prevention and control and clinical treatment, traditional Chinese medicine played a huge role in China. Here, we screened out six monomer compounds, including artemether, artesunate, arteannuin B, echinatin, licochalcone B and andrographolide, with excellent anti-SARS-CoV-2 and anti-GX_P2V activity from Anti-COVID-19 Traditional Chinese Medicine Compound Library containing 389 monomer compounds extracted from traditional Chinese medicine prescriptions "three formulas and three drugs". Our discovery preliminary proved the stage of action of those compounds against SARS-CoV-2 and provided inspiration for further research and clinical applications.


Assuntos
COVID-19 , SARS-CoV-2 , Artemeter , Artemisininas , Artesunato , Chalconas , Diterpenos , Humanos
7.
Analyst ; 146(19): 6026-6034, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34505858

RESUMO

The ongoing outbreaks of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have resulted in unprecedented challenges to global health. To effectively contain the COVID-19 transmission, rapid tests for detecting existing SARS-CoV-2 infections and assessing virus spread are critical. To address the huge need for ever-increasing tests, we developed a facile all-in-one nucleic acid testing assay by combining Si-OH activated glass bead (aGB)-based viral RNA fast extraction and in situ colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) detection in a single tube. aGBs demonstrate a strong ability to capture viral RNA in a guanidinium-based lysis buffer, and the purified aGBs/RNA composite, without RNA elution step, could be directly used to perform RT-LAMP assay. The assay was well characterized by using a novel SARS-CoV-2-like coronavirus GX/P2V, and showed a limit of detection (LOD) of 15 copies per µL in simulated clinical samples within 50 min. We further demonstrated our assay by testing simulated SARS-CoV-2 pseudovirus samples, showing an LOD of 32 copies per µL and high specificity without cross-reactivity with the most closely related GX/P2V or host DNA/RNA. The all-in-one approach developed in this study has the potential as a simple, scalable, and time-saving alternative for point-of-care testing of SARS-CoV-2 in low-income regions, as well as a promising tool for at-home testing.


Assuntos
COVID-19 , SARS-CoV-2 , Colorimetria , Humanos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Testes Imediatos , RNA Viral/genética , Sensibilidade e Especificidade
8.
Aging Med (Milton) ; 4(3): 162-168, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34553112

RESUMO

Objective: Observe the influence of oral nutritional agents rich in soluble dietary (enteral nutritional suspension [TPF-DM]) on intestinal flora of elderly male subjects with malnutrition. Method: Seventy-eight subjects with good nutrition were considered as the healthy control group. Twenty-eight male subjects who had malnutrition and were older than 70 years were included and randomly divided into the short-term (3 months) intervention group (n = 20) and the long-term (12 months) group (n = 8). They were provided with enteral nutritional suspension (TPF-DM) 500 mL/day or maximum tolerance dose, so as to observe the changes in nutrition-related indexes and intestinal flora after the elderly take enteral nutritional suspension (TPF-DM). Results: (1) For elderly male subjects with malnutrition, their body weight, body mass index, hemoglobin, total protein, and albumin were significantly lower than the control group with favorable nutrition. (2) There were obvious differences in intestinal flora between healthy elderly male subjects and those with malnutrition. After the treatment of enteral nutritional suspension (TPF-DM), intestinal flora of the malnourished elderly subjects showed recovery toward the healthy elderly subjects. The obvious gradient changes of the flora were mainly in the bacteroidetes, firmicutes, and proteobacteria phyla, and the relative abundance of CAG2 clusters in the malnourished group was higher than that in the healthy control group, and the relative abundance decreased after long-term treatment, and the change approached the healthy control group. The relative abundance of CAG3 and CAG6 clusters in the malnourished group was lower than that in the healthy control group, and the relative abundance increased after long-term treatment, and the change approached the healthy control group. Conclusion: Malnutrition has obvious impact on intestinal flora of the elderly. Enteral nutritional suspension (TPF-DM) not only prevents the further decline in the state of nutrition but also helps the recovery in intestinal flora of the elderly. Long-term application can produce better effects.

11.
Virus Res ; 305: 198569, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34555434

RESUMO

Temperate phages play an important role in the evolution of bacteria. So far, lytic phages have been wildly reported, but there is still limited knowledge regarding temperate phages in the genome of pathogenic Staphylococcus caprae. Here we present the characteristics and genome analysis of a novel bacteriophage IME1323_01, which is the first isolated bacteriophage of S. caprae. The phage genome is a 44282-bp linear dsDNA molecule with a GC content of 34.18%, which is similar to its host. The genome of IME1323_01 is most closely related with that of temperate phage IME1318_01, whereas the homology coverage is just 34%. Genome and proteome analyses confirmed the lysogenic nature of phage IME1323_01, which encodes the typical lysogen-related proteins integrase, CI, Cro, and anti-repressor proteins. Genomic and phylogenetic analysis revealed that phage IME1323_01 is a newly discovered phage, which belongs to subfamily Azeredovirinae in the family Siphoviridae. The goal of this study is to increase our knowledge about the phages of S. caprae and expand our armamentarium against the escalating threat of pathogenic bacteria.

12.
Front Cell Infect Microbiol ; 11: 728415, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34466405

RESUMO

Background: The second human pegivirus (HPgV-2) and hepatitis C virus (HCV) belong to the Flaviviridae family and share some common genome features. However, the two viruses exhibit significantly different genetic diversity. The comparison of intrahost dynamics of HPgV-2 and HCV that mainly reflect virus-host interactions is needed to elucidate their intrahost difference of genetic diversity and the possible mechanisms. Methods: Intrahost single nucleotide variations (iSNVs) were identified by means of next-generation sequencing from both cross-sectional and longitudinal samples from HPgV-2- and HCV-coinfected patients. The levels of human cytokines were quantified in the patient before and after HCV elimination by the treatment of direct-acting antivirals (DAA). Results: Unlike HCV, the viral sequences of HPgV-2 are highly conserved among HPgV-2-infected patients. However, iSNV analysis confirmed the intrahost variation or quasispecies of HPgV-2. Almost all iSNVs of HPgV-2 did not accumulate or transmit within host over time, which may explain the highly conserved HPgV-2 consensus sequence. Intrahost variation of HPgV-2 mainly causes nucleotide transition in particular at the 3rd codon position and synonymous substitutions, indicating purifying or negative selection posed by host immune system. Cytokine data further indicate that HPgV-2 infection alone may not efficiently stimulate innate immune responses since proinflammatory cytokine expression dramatically decreased with elimination of HCV. Conclusion: This study provided new insights into the intrahost genomic variations and evolutionary dynamics of HPgV-2 as well as the impact of host immune selection and virus polymerase on virus evolution. The different genetic diversity of HPgV-2 and HCV makes HPgV-2 a potential new model to investigate RNA virus diversity and the mechanism of viral polymerase in modulating virus replication.


Assuntos
Infecções por Flaviviridae , Hepatite C Crônica , Hepatite C , Antivirais , Estudos Transversais , Infecções por Flaviviridae/complicações , Hepacivirus/genética , Hepatite C/complicações , Humanos , Pegivirus , Filogenia , RNA Viral
13.
Pharmaceutics ; 13(8)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34452123

RESUMO

The feasibility of using respirable bacteriophage (phage) powder to treat lung infections has been demonstrated in animal models and clinical studies. This work investigated the influence of formulation compositions and excipient concentrations on the aerosol performance and storage stability of phage powder. An anti-Acinetobacter baumannii phage vB_AbaM-IME-AB406 was incorporated into dry powders consisting of trehalose, mannitol and L-leucine for the first time. The phage stability upon the spray-drying process, room temperature storage and powder dispersion under different humidity conditions were assessed. In general, powders prepared with higher mannitol content (40% of the total solids) showed a lower degree of particle merging and no sense of stickiness during sample handling. These formulations also provided better storage stability of phage with no further titer loss after 1 month and <1 log titer loss in 6 months at high excipient concentration. Mannitol improved the dispersibility of phage powders, but the in vitro lung dose dropped sharply after exposure to high-humidity condition (65% RH) for formulations with 20% mannitol. While previously collected knowledge on phage powder preparation could be largely extended to formulate A. baumannii phage into inhalable dry powders, the environmental humidity may have great impacts on the stability and dispersion of phage; therefore, specific attention is required when optimizing phage powder formulations for global distribution.

14.
Virus Res ; 305: 198546, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34400225

RESUMO

Noroviruses can infect humans and a wide variety of other mammalian hosts, causing varying degrees of diarrhea. In this study, two novel norovirus genomes were identified for the first time in farmed raccoon dogs, designated as raccoon dog noroviruses BUCT-K1 and BUCT-K4. Neither the farmers nor the raccoon dogs had symptoms (e.g., diarrhea) at the time of sample collection. We collected 14 stool samples from two farms, and 85.7% (12/14) of the samples were norovirus positive by RT-PCR. The two norovirus genomes have the highest identity to Dog/Z7/19/CH, suggesting that the norovirus might have been transmitted from dogs to raccoon dogs. Genomic and evolutionary analyses indicated that different directions of evolution occurred following the spread of the norovirus to the raccoon dogs. This study has increased knowledge of norovirus-infected animal species and has provided additional information on the norovirus family.

15.
Arch Virol ; 166(9): 2505-2520, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34236511

RESUMO

In this study, a novel Escherichia coli-specific bacteriophage, vB_EcoM_IME392, was isolated from chicken farm sewage in Qingdao, China. The genome of IME392 was found by next-generation sequencing to be 116,460 base pairs in length with a G+C content of 45.4% (GenBank accession number MH719082). BLASTn results revealed that only 2% of the genome sequence of IME392 shows sequence similarity to known phage sequences in the GenBank database, which indicates that IME392 is a novel bacteriophage. Transmission electron microscopy showed that IME392 belongs to the family Myoviridae. The host range, the multiplicity of infection, and a one-step growth curve were also determined.


Assuntos
Colífagos/genética , Escherichia coli/virologia , Myoviridae/genética , Sequenciamento Completo do Genoma , Composição de Bases , Sequência de Bases , China , Mapeamento Cromossômico , Colífagos/classificação , DNA Viral/genética , Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Especificidade de Hospedeiro , Concentração de Íons de Hidrogênio , Myoviridae/classificação , Filogenia , Proteômica , Esgotos/virologia , Temperatura
16.
Virus Res ; 303: 198506, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34271040

RESUMO

Carbapenem-resistant Klebsiella pneumoniae (CRKP) have spread globally and led to the limited choice of antimicrobial treatment of K. pneumoniae-induced infections. Bacteriophages are considered as an effective strategy against bacterial infections. In this study, we isolated a novel Klebsiella phage BUCT556A with lytic activity against KPC-producing K. pneumoniae, which was a multi-drug resistant isolate. Phage BUCT556A had a symmetrical head and a long, non-contractile tail, belonging to the family Siphoviridae, order Caudoviridae. Phage BUCT556A had a relatively narrow host range, and a medium burst size of 91 PFU/cell. It was stable at broad temperature/pH range, and exhibited good tolerance to chloroform. The genome of phage BUCT556A was a 49, 376-bp linear double-stranded DNA molecule with average G + C content of 50.2%, and contained 75 open reading frames. There was no tRNA, antibiotic resistance, toxin, virulence related genes or lysogen-formation gene clusters detected in the genome of phage BUCT556A. Phylogenetic analyses based on the major capsid protein Mcp suggested that this phage had a close relationship with Klebsiella phage KLPN1. Together, through phenotypic combined with genomic DNA sequencing and analyses, our study suggests that phage BUCT556A has the potential to be used as a bacterial treatment tool for multidrug-resistant strains K. pneumoniae.

17.
BMC Biol ; 19(1): 137, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34225711

RESUMO

BACKGROUND: Lactose malabsorption occurs in around 68% of the world's population, causing lactose intolerance (LI) symptoms, such as abdominal pain, bloating, and diarrhea. To alleviate LI, previous studies have mainly focused on strengthening intestinal ß-galactosidase activity while neglecting the inconspicuous drop in the colon pH caused by the fermentation of non-hydrolyzed lactose by the gut microbes. A drop in colon pH will reduce the intestinal ß-galactosidase activity and influence intestinal homeostasis. RESULTS: Here, we synthesized a tri-stable-switch circuit equipped with high ß-galactosidase activity and pH rescue ability. This circuit can switch in functionality between the expression of ß-galactosidase and expression of L-lactate dehydrogenase in response to an intestinal lactose signal and intestinal pH signal, respectively. We confirmed that the circuit functionality was efficient in bacterial cultures at a range of pH levels, and in preventing a drop in pH and ß-galactosidase activity after lactose administration to mice. An impact of the circuit on gut microbiota composition was also indicated. CONCLUSIONS: Due to its ability to flexibly adapt to environmental variation, in particular to stabilize colon pH and maintain ß-galactosidase activity after lactose influx, the tri-stable-switch circuit can serve as a promising prototype for the relief of lactose intolerance.

19.
Curr Microbiol ; 78(8): 3192-3200, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34213617

RESUMO

Xanthomonas oryzae pv. oryzae (X. oryzae) is a bacterial pathovar of rice diseases all over the world. Owing to emerging antibacterial resistance, phage therapies have gained significant attention to treat various bacterial infections. Nevertheless, comprehensive research is needed for their use as a safe biocontrol agent. In this study, isolation and characterization of a novel phage Xoo-sp15, that infects X. oryzae was ascertained through experimental and bioinformatics analyses to determine its virulent potency and reliability. High throughput sequencing demonstrated that Xoo-sp15 has a dsDNA genome with a total size of 157,091 bp and 39.9% GC content lower than its host (63.6%). Morphological and phylogenetic analyses characterized it as a new member of the Bastille-like group within the family Herelleviridae. In silico analysis revealed that it contains 229 open reading frames and 16 tRNAs. Additionally, this novel phage does not contain any resistant determinants and can infect nine X. oryzae strains. Therefore, Xoo-sp15 has the potential to serve as a novel candidate for phage therapy.


Assuntos
Bacteriófagos , Oryza , Xanthomonas , Bacteriófagos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Oryza/genética , Filogenia , Doenças das Plantas , Reprodutibilidade dos Testes , Xanthomonas/genética
20.
Front Microbiol ; 12: 668319, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220752

RESUMO

Vibrio alginolyticus is one of the most important of pathogens that can infect humans and a variety of aquatic animals, and it can cause food poisoning and septicemia in humans. Widely used antibiotics are gradually losing their usefulness, and phages are gaining more attention as new antibacterial strategies. To have more potential strategies for controlling pathogenic bacteria, we isolated a novel V. alginolyticus phage BUCT549 from seafood market sewage. It was classified as a new member of the family Siphoviridae by transmission electron microscopy and a phylogenetic tree. We propose creating a new genus for BUCT549 based on the intergenomic similarities (maximum is 56%) obtained from VIRIDIC calculations. Phage BUCT549 could be used for phage therapy due to its stability in a wide pH (3.0-11.0) range and high-temperature (up to 60°C) environment. It had a latent period of 30-40 min and a burst size of 141 PFU/infected bacterium. In the phylogenetic tree based on a terminase large subunit, BUCT549 was closely related to eight Vibrio phages with different species of host. Meanwhile, our experiments proved that BUCT549 has the ability to infect a strain of Vibrio parahaemolyticus. A coevolution experiment determined that three strains of tolerant V. alginolyticus evaded phage infestation by mutating the MSHA-related membrane protein expression genes, which caused the loss of flagellum. This research on novel phage identification and the mechanism of infestation will help phages to become an integral part of the strategy for biological control agents.

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