SARS-CoV-2 infection reduces human nasopharyngeal commensal microbiome with inclusion of pathobionts

AbstractThe microbiota of the nasopharyngeal tract (NT) play a role in host immunity against respiratory infectious diseases. However, scant information is available on interactions of SARS-CoV-2 with the nasopharyngeal microbiome. This study characterizes the effects of SARS-CoV-2 infection on human nasopharyngeal microbiomes and their relevant metabolic functions. Twenty-two (n = 22) nasopharyngeal swab samples (including COVID-19 patients = 8, recovered humans = 7, and healthy people = 7) were collected, and underwent to RNAseq-based metagenomic investigation. Our RNAseq data mapped to 2281 bacterial species (including 1477, 919 and 676 in healthy, COVID-19 and recovered metagenomes, respectively) indicating a distinct microbiome dysbiosis. The COVID-19 and recovered samples included 67% and 77% opportunistic bacterial species, respectively compared to healthy controls. Notably, 79% commensal bacterial species found in healthy controls were not detected in COVID-19 and recovered people. Similar dysbiosis was also found in viral and archaeal fraction of the nasopharyngeal microbiomes. We also detected several altered metabolic pathways and functional genes in the progression and pathophysiology of COVID-19. The nasopharyngeal microbiome dysbiosis and their genomic features determined by our RNAseq analyses shed light on early interactions of SARS-CoV-2 with the nasopharyngeal resident microbiota that might be helpful for developing microbiome-based diagnostics and therapeutics for this novel pandemic disease.

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Nephromyces represents a diverse and novel lineage of the Apicomplexa that has retained apicoplasts

Genome Biology and Evolution ◽

10.1093/gbe/evz155 ◽

2019 ◽

Cited By ~ 4

Author(s):

Sergio A Muñoz-Gómez ◽

Keira Durnin ◽

Laura Eme ◽

Christopher Paight ◽

Christopher E Lane ◽

...

Keyword(s):

Life Style ◽

Metabolic Pathways ◽

Evolutionary History ◽

Phylogenetic Analyses ◽

Phylogenetic Position ◽

Biosynthetic Pathways ◽

History Of ◽

Sea Squirts ◽

Shed Light ◽

Apicoplast Genome

Abstract A most interesting exception within the parasitic Apicomplexa is Nephromyces, an extracellular, probably mutualistic, endosymbiont found living inside molgulid ascidian tunicates (i.e., sea squirts). Even though Nephromyces is now known to be an apicomplexan, many other questions about its nature remain unanswered. To gain further insights into the biology and evolutionary history of this unusual apicomplexan, we aimed to (1) find the precise phylogenetic position of Nephromyces within the Apicomplexa, (2) search for the apicoplast genome of Nephromyces, and (3) infer the major metabolic pathways in the apicoplast of Nephromyces. To do this, we sequenced a metagenome and a metatranscriptome from the molgulid renal sac, the specialized habitat where Nephromyces thrives. Our phylogenetic analyses of conserved nucleus-encoded genes robustly suggest that Nephromyces is a novel lineage sister to the Hematozoa, which comprises both the Haemosporidia (e.g., Plasmodium) and the Piroplasmida (e.g., Babesia and Theileria). Furthermore, a survey of the renal sac metagenome revealed 13 small contigs that closely resemble the genomes of the non-photosynthetic reduced plastids, or apicoplasts, of other apicomplexans. We show that these apicoplast genomes correspond to a diverse set of most closely related but genetically divergent Nephromyces lineages that co-inhabit a single tunicate host. In addition, the apicoplast of Nephromyces appears to have retained all biosynthetic pathways inferred to have been ancestral to parasitic apicomplexans. Our results shed light on the evolutionary history of the only probably mutualistic apicomplexan known, Nephromyces, and provide context for a better understanding of its life style and intricate symbiosis.

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New complete genome sequences of human rhinoviruses shed light on their phylogeny and genomic features

BMC Genomics ◽

10.1186/1471-2164-8-224 ◽

2007 ◽

Vol 8 (1) ◽

pp. 224 ◽

Cited By ~ 45

Author(s):

Caroline Tapparel ◽

Thomas Junier ◽

Daniel Gerlach ◽

Samuel Cordey ◽

Sandra Van Belle ◽

...

Keyword(s):

Complete Genome ◽

Genome Sequences ◽

Genomic Features ◽

Shed Light

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Alterations of the Fecal Microbiota in Chinese Patients With Multiple Sclerosis

Frontiers in Immunology ◽

10.3389/fimmu.2020.590783 ◽

2020 ◽

Vol 11 ◽

Author(s):

Zongxin Ling ◽

Yiwen Cheng ◽

Xiumei Yan ◽

Li Shao ◽

Xia Liu ◽

...

Keyword(s):

Multiple Sclerosis ◽

Intestinal Microbiota ◽

Area Under The Curve ◽

Fecal Microbiota ◽

Host Immunity ◽

Chinese Patients ◽

Healthy Controls ◽

Cytokines And Chemokines ◽

Functional Bacteria ◽

Functional Profiles

Mounting evidence indicates that alterations in the intestinal microbiota may be associated with neurological disorders such as multiple sclerosis (MS). MS is a putative autoimmune disease of the central nervous system. However, it has not been determined whether the intestinal microbiota and host immune status are altered in Chinese patients with stable MS. In our study, 22 Chinese patients with stable MS and 33 healthy controls were enrolled for fecal microbiota analysis and host immunity evaluation. The microbial diversity and composition, bacterial co-occurrence correlations, predictive functional profiles, and microbiota-cytokine correlations between the two groups were compared. We observed that while the overall structure of the fecal microbiota did not change significantly, the abundances of several key functional bacteria, primarily Faecalibacterium, decreased remarkably. Faecalibacterium and Granulicatella could be used to distinguish between patients with MS and healthy controls with an area under the curve of 0.832. PiCRUSt analysis revealed that genes associated with fructose, mannose, and fatty acid metabolism were significantly enriched in the MS microbiota. In addition, we also observed that the levels of several pro- and anti-inflammatory cytokines and chemokines, such as IL-1ra, IL-8, IL-17, and TNF-α changed observably, and the abundances of key functional bacteria like butyrate producers correlated with the changes in the cytokine levels. Our present study indicated that altered composition of the fecal microbiota might play vital roles in the etiopathogenesis of MS by regulating host immunity, which suggests that microbiota-targeting patient-tailored early intervention techniques might serve as novel therapeutic approaches for MS.

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Role of bacteria in oral carcinogenesis

South Asian Journal of Cancer ◽

10.4103/2278-330x.103719 ◽

2012 ◽

Vol 01 (02) ◽

pp. 78-83 ◽

Cited By ~ 9

Author(s):

R Rajeev ◽

Kanaram Choudhary ◽

Swagatika Panda ◽

Neha Gandhi

Keyword(s):

Metabolic Pathways ◽

Bacterial Species ◽

Cancer Therapeutics ◽

Microbial Populations ◽

Genetic Mutations ◽

Oral Carcinogenesis ◽

Common Cancer ◽

Indian Men ◽

Oral Microorganisms

AbstractOral cancer is the most common cancer diagnosed in Indian men and is the leading cause of cancer deaths. It is considered as a multistep and multifactorial disease. Besides accumulation of genetic mutations, numerous other carcinogens are involved. In this category, viral and chemical carcinogens are well studied and documented. However, in the oral cavity, the role of microbiota in carcinogenesis is not known. Microbial populations on mouth mucosa differ between healthy and malignant sites, and certain oral bacterial species have been linked with malignancies, but the evidence is still weak in this respect. Nevertheless, oral microorganisms inevitably up-regulate cytokines and other inflammatory mediators that affect the complex metabolic pathways, and may thus be involved in carcinogenesis. Poor oral health associates statistically with prevalence of many types of cancer such as pancreatic and gastrointestinal cancer. This review presents possible carcinogenesis pathway involved in bacterial carcinogenesis, commonly implicated bacteria in oral carcinogenesis, and their role in cancer therapeutics as well.

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Redox Homeostasis and Metabolism in Cancer: A Complex Mechanism and Potential Targeted Therapeutics

International Journal of Molecular Sciences ◽

10.3390/ijms21093100 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3100 ◽

Cited By ~ 1

Author(s):

Alia Ghoneum ◽

Ammar Yasser Abdulfattah ◽

Bailey Olivia Warren ◽

Junjun Shu ◽

Neveen Said

Keyword(s):

Cancer Cells ◽

Cancer Progression ◽

Metabolic Pathways ◽

Redox Homeostasis ◽

Ros Production ◽

Biological Processes ◽

Survival Pathways ◽

Oncogenic Mutations ◽

And Oxidative Stress ◽

Shed Light

Reactive Oxygen Species or “ROS” encompass several molecules derived from oxygen that can oxidize other molecules and subsequently transition rapidly between species. The key roles of ROS in biological processes are cell signaling, biosynthetic processes, and host defense. In cancer cells, increased ROS production and oxidative stress are instigated by carcinogens, oncogenic mutations, and importantly, metabolic reprograming of the rapidly proliferating cancer cells. Increased ROS production activates myriad downstream survival pathways that further cancer progression and metastasis. In this review, we highlight the relation between ROS, the metabolic programing of cancer, and stromal and immune cells with emphasis on and the transcription machinery involved in redox homeostasis, metabolic programing and malignant phenotype. We also shed light on the therapeutic targeting of metabolic pathways generating ROS as we investigate: Orlistat, Biguandes, AICAR, 2 Deoxyglucose, CPI-613, and Etomoxir.

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The composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot study

Microbiome ◽

10.1186/s40168-019-0753-z ◽

2019 ◽

Vol 7 (1) ◽

Cited By ~ 4

Author(s):

Josef Wagner ◽

Ewan M. Harrison ◽

Marcos Martinez Del Pero ◽

Beth Blane ◽

Gert Mayer ◽

...

Keyword(s):

Granulomatosis With Polyangiitis ◽

Sequence Data ◽

Bacterial Species ◽

Vitamin B ◽

Diversity Analysis ◽

Healthy Controls ◽

Functional Protein ◽

Metagenomic Sequence ◽

Metagenomic Sequence Data ◽

Nasal Microbiota

Abstract Background Ear, nose and throat involvement in granulomatosis with polyangiitis (GPA) is frequently the initial disease manifestation. Previous investigations have observed a higher prevalence of Staphylococcus aureus in patients with GPA, and chronic nasal carriage has been linked with an increased risk of disease relapse. In this cross-sectional study, we investigated changes in the nasal microbiota including a detailed analysis of Staphylococcus spp. by shotgun metagenomics in patients with active and inactive granulomatosis with polyangiitis (GPA). Shotgun metagenomic sequence data were also used to identify protein-encoding genes within the SEED database, and the abundance of proteins then correlated with the presence of bacterial species on an annotated heatmap. Results The presence of S. aureus in the nose as assessed by culture was more frequently detected in patients with active GPA (66.7%) compared with inactive GPA (34.1%). Beta diversity analysis of nasal microbiota by bacterial 16S rRNA profiling revealed a different composition between GPA patients and healthy controls (P = 0.039). Beta diversity analysis of shotgun metagenomic sequence data for Staphylococcus spp. revealed a different composition between active GPA patients and healthy controls and disease controls (P = 0.0007 and P = 0.0023, respectively), and between healthy controls and inactive GPA patients and household controls (P = 0.0168 and P = 0.0168, respectively). Patients with active GPA had a higher abundance of S. aureus, mirroring the culture data, while healthy controls had a higher abundance of S. epidermidis. Staphylococcus pseudintermedius, generally assumed to be a pathogen of cats and dogs, showed an abundance of 13% among the Staphylococcus spp. in our cohort. During long-term follow-up of patients with inactive GPA at baseline, a higher S. aureus abundance was not associated with an increased relapse risk. Functional analyses identified ten SEED protein subsystems that differed between the groups. Most significant associations were related to chorismate synthesis and involved in the vitamin B12 pathway. Conclusion Our data revealed a distinct dysbiosis of the nasal microbiota in GPA patients compared with disease and healthy controls. Metagenomic sequencing demonstrated that this dysbiosis in active GPA patients is manifested by increased abundance of S. aureus and a depletion of S. epidermidis, further demonstrating the antagonist relationships between these species. SEED functional protein subsystem analysis identified an association between the unique bacterial nasal microbiota clusters seen mainly in GPA patients and an elevated abundance of genes associated with chorismate synthesis and vitamin B12 pathways. Further studies are required to further elucidate the relationship between the biosynthesis genes and the associated bacterial species.

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Host and body site-specific adaptation of Lactobacillus crispatus genomes

NAR Genomics and Bioinformatics ◽

10.1093/nargab/lqaa001 ◽

2020 ◽

Vol 2 (1) ◽

Cited By ~ 2

Author(s):

Meichen Pan ◽

Claudio Hidalgo-Cantabrana ◽

Rodolphe Barrangou

Keyword(s):

Ecological Niches ◽

Human Gut ◽

Important Species ◽

Genomic Features ◽

Specific Adaptation ◽

Lactobacillus Crispatus ◽

Vaginal Tract ◽

Functional Features ◽

In Silico Analyses ◽

Shed Light

Abstract Lactobacillus crispatus is a common inhabitant of both healthy poultry gut and human vaginal tract, and the absence of this species has been associated with a higher risk of developing infectious diseases. In this study, we analyzed 105 L. crispatus genomes isolated from a variety of ecological niches, including the human vaginal tract, human gut, chicken gut and turkey gut, to shed light on the genetic and functional features that drive evolution and adaptation of this important species. We performed in silico analyses to identify the pan and core genomes of L. crispatus, and to reveal the genomic differences and similarities associated with their origins of isolation. Our results demonstrated that, although a significant portion of the genomic content is conserved, human and poultry L. crispatus isolates evolved to encompass different genomic features (e.g. carbohydrate usage, CRISPR–Cas immune systems, prophage occurrence) in order to thrive in different environmental niches. We also observed that chicken and turkey L. crispatus isolates can be differentiated based on their genomic information, suggesting significant differences may exist between these two poultry gut niches. These results provide insights into host and niche-specific adaptation patterns in species of human and animal importance.

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Molecular insights into the genome dynamics and interactions between core and acquired genomes ofVibrio cholerae

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2006283117 ◽

2020 ◽

Vol 117 (38) ◽

pp. 23762-23773

Author(s):

Archana Pant ◽

Satyabrata Bag ◽

Bipasa Saha ◽

Jyoti Verma ◽

Pawan Kumar ◽

...

Keyword(s):

Bacterial Species ◽

Bacterial Genome ◽

Genomic Islands ◽

Host Bacterium ◽

Metabolic Functions ◽

Bipartite Genome ◽

Ctx Prophage ◽

Integrative Conjugative Elements

Bacterial species are hosts to horizontally acquired mobile genetic elements (MGEs), which encode virulence, toxin, antimicrobial resistance, and other metabolic functions. The bipartite genome ofVibrio choleraeharbors sporadic and conserved MGEs that contribute in the disease development and survival of the pathogens. For a comprehensive understanding of dynamics of MGEs in the bacterial genome, we engineered the genome ofV. choleraeand examined in vitro and in vivo stability of genomic islands (GIs), integrative conjugative elements (ICEs), and prophages. Recombinant vectors carrying the integration module of these GIs, ICE and CTXΦ, helped us to understand the efficiency of integrations of MGEs in theV. choleraechromosome. We have deleted more than 250 acquired genes from 6 different loci in theV. choleraechromosome and showed contribution of CTX prophage in the essentiality of SOS response master regulator LexA, which is otherwise not essential for viability in other bacteria, includingEscherichia coli. In addition, we observed that the core genome-encoded RecA helps CTXΦ to bypassV. choleraeimmunity and allow it to replicate in the host bacterium in the presence of similar prophage in the chromosome. Finally, our proteomics analysis reveals the importance of MGEs in modulating the levels of cellular proteome. This study engineered the genome ofV. choleraeto remove all of the GIs, ICEs, and prophages and revealed important interactions between core and acquired genomes.

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Heterozygous, Polyploid, Giant Bacterium, Achromatium, Possesses an Identical Functional Inventory Worldwide across Drastically Different Ecosystems

Molecular Biology and Evolution ◽

10.1093/molbev/msaa273 ◽

2020 ◽

Author(s):

Danny Ionescu ◽

Luca Zoccarato ◽

Artur Zaduryan ◽

Sina Schorn ◽

Mina Bizic ◽

...

Keyword(s):

Species Concept ◽

Single Cells ◽

Bacterial Species ◽

Expression Patterns ◽

Allelic Diversity ◽

Evolutionary Mechanisms ◽

Genomic Features ◽

Bacterial Speciation ◽

Depth Ranges ◽

Functional Versatility

Abstract Achromatium is large, hyperpolyploid and the only known heterozygous bacterium. Single cells contain approximately 300 different chromosomes with allelic diversity far exceeding that typically harbored by single bacteria genera. Surveying all publicly available sediment sequence archives, we show that Achromatium is common worldwide, spanning temperature, salinity, pH, and depth ranges normally resulting in bacterial speciation. Although saline and freshwater Achromatium spp. appear phylogenetically separated, the genus Achromatium contains a globally identical, complete functional inventory regardless of habitat. Achromatium spp. cells from differing ecosystems (e.g., from freshwater to saline) are, unexpectedly, equally functionally equipped but differ in gene expression patterns by transcribing only relevant genes. We suggest that environmental adaptation occurs by increasing the copy number of relevant genes across the cell’s hundreds of chromosomes, without losing irrelevant ones, thus maintaining the ability to survive in any ecosystem type. The functional versatility of Achromatium and its genomic features reveal alternative genetic and evolutionary mechanisms, expanding our understanding of the role and evolution of polyploidy in bacteria while challenging the bacterial species concept and drivers of bacterial speciation.

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P003 Metabolomics for improved patient stratification in inflammatory bowel disease: Characterisation of the ulcerative colitis metabolome

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.132 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S130-S131

Author(s):

J Diab ◽

T Hansen ◽

R Goll ◽

H Stenlund ◽

E Jensen ◽

...

Keyword(s):

Mass Spectrometry ◽

Ulcerative Colitis ◽

Amino Acid ◽

Metabolic Pathways ◽

Personalised Medicine ◽

Healthy Controls ◽

Patient Stratification ◽

Metabolomic Profile ◽

Metabolic Signature ◽

Treatment Naïve

Abstract Background The onset of ulcerative colitis (UC) is characterised by a dysregulated mucosal immune response triggered by several genetic and environmental factors in the context of host-microbe interaction. This complexity makes UC ideal for metabolomic studies to unravel the disease pathobiology and to improve the patient stratification strategies toward personalised medicine. This study aims to explore the mucosal metabolomic profile in treatment-naïve and deep remission UC patients, and to define the metabolic signature of UC. Methods Treatment-naive UC patients (n = 18), UC patients in deep remission (n = 10), and healthy volunteers (n = 14) were recruited. Mucosa biopsies were collected during colonoscopy. The UC activity and the state of deep remission were assessed by endoscopy, histology, and by measuring TNF gene expression. Metabolomic analysis was performed by combined gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS) and ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). In total, 177 metabolites from 50 metabolic pathways were identified. Results Multivariate data analysis revealed a distinct metabolomic profile in inflamed mucosa taken from treatment- naïve UC patients compared with non-inflamed mucosa taken from UC remission patients and healthy controls. The mucosal metabolome in UC remission patients differed to a lesser extent from the healthy controls. The most prominent metabolome changes among the study groups were in lysophosphatidylcholine, acylcarnitine, and amino acid profiles. Several metabolic pathways were perturbed, ranging from amino acid metabolism (such as tryptophan metabolism, and alanine, aspartate and glutamate metabolism) to antioxidant defence pathway (glutathione pathway). Furthermore, the pathway analysis revealed a disruption in the long-and short-chain fatty acid (LCFA and SCFA) metabolism, namely linoleic metabolism and butyrate metabolism. Conclusion The mucosal metabolomic profiling revealed a metabolic signature during the onset of UC, and reflected the homeostatic disturbance in the gut. The altered metabolic pathways highlight the importance of system biology approaches to identify key drivers of IBD pathogenesis which prerequisite personalised treatment.

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