-
Haematologica Dec 2023Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a Hodgkin lymphoma expressing functional B-cell receptors (BCR). Recently, we described a dual stimulation...
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a Hodgkin lymphoma expressing functional B-cell receptors (BCR). Recently, we described a dual stimulation model of IgD+ lymphocyte-predominant cells by Moraxella catarrhalis antigen RpoC and its superantigen MID/hag, associated with extralong CDR3 and HLA-DRB1*04 or HLADRB1* 07 haplotype. The aim of the present study was to extend the antigen screening to further bacteria and viruses. The fragment antibody-binding (Fab) regions of seven new and 15 previously reported cases were analyzed. The reactivity of non-Moraxella spp.-reactive Fab regions against lysates of Rothia mucilaginosa was observed in 5/22 (22.7%) cases. Galactofuranosyl transferase (Gltf) and 2,3-butanediol dehydrogenase (Bdh) of R. mucilaginosa were identified by comparative silver- and immuno-staining in two-dimensional gels, with subsequent mass spectrometry and validation by western blots and enzyme-linked immunosorbent assay. Both R. mucilaginosa Gltf and Bdh induced BCR pathway activation and proliferation in vitro. Apoptosis was induced by recombinant Gltf/ETA'-immunotoxin conjugates in DEV cells expressing recombinant R. mucilaginosa-reactive BCR. Reactivity against M. catarrhalis RpoC was confirmed in 3/7 newly expressed BCR (total 10/22 reactive to Moraxella spp.), resulting in 15/22 (68.2%) cases with BCR reactivity against defined bacterial antigens. These findings strengthen the hypothesis of bacterial trigger contributing to subsets of NLPHL.
Topics: Humans; Hodgkin Disease; Receptors, Antigen, B-Cell; Micrococcaceae; Lymphocytes
PubMed: 37139600
DOI: 10.3324/haematol.2023.282698 -
Microbiology Spectrum Jun 2024Cystic fibrosis (CF), an inherited genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene, results in sticky and thick...
Cystic fibrosis (CF), an inherited genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene, results in sticky and thick mucosal fluids. This environment facilitates the colonization of various microorganisms, some of which can cause acute and chronic lung infections, while others may positively impact the disease. , an oral commensal, is relatively abundant in the lungs of CF patients. Recent studies have unveiled its anti-inflammatory properties using three-dimensional lung epithelial cell cultures and mouse models relevant to chronic lung diseases. Apart from this, has been associated with severe infections. However, its metabolic capabilities and genotype-phenotype relationships remain largely unknown. To gain insights into its cellular metabolism and genetic content, we developed the first manually curated genome-scale metabolic model, RM23NL. Through growth kinetics and high-throughput phenotypic microarray testings, we defined its complete catabolic phenome. Subsequently, we assessed the model's effectiveness in accurately predicting growth behaviors and utilizing multiple substrates. We used constraint-based modeling techniques to formulate novel hypotheses that could expedite the development of antimicrobial strategies. More specifically, we detected putative essential genes and assessed their effect on metabolism under varying nutritional conditions. These predictions could offer novel potential antimicrobial targets without laborious large-scale screening of knockouts and mutant transposon libraries. Overall, RM23NL demonstrates a solid capability to predict cellular phenotypes and holds immense potential as a valuable resource for accurate predictions in advancing antimicrobial therapies. Moreover, it can guide metabolic engineering to tailor 's metabolism for desired performance.IMPORTANCECystic fibrosis (CF) is a genetic disorder characterized by thick mucosal secretions, leading to chronic lung infections. is a common bacterium found in various parts of the human body, acting as a normal part of the flora. In people with weakened immune systems, it can become an opportunistic pathogen, while it is prevalent and active in CF airways. Recent studies have highlighted its anti-inflammatory properties in the lower pulmonary system, indicating the intricate relationship between microbes and human health. Herein, we have developed the first manually curated metabolic model of . Our study examined the previously unknown relationships between the bacterium's genotype and phenotype and identified essential genes that impact the metabolism under various conditions. With this, we opt for paving the way for developing new strategies in antimicrobial therapy and metabolic engineering, leading to enhanced therapeutic outcomes in cystic fibrosis and related conditions.
Topics: Cystic Fibrosis; Humans; Micrococcaceae; Genome, Bacterial; Genes, Essential; Animals; Mice; Phenotype
PubMed: 38652457
DOI: 10.1128/spectrum.04006-23 -
Cells Aug 2023is an opportunistic pathogen, particularly life-threatening for the immunocompromised. It is associated with pneumonia, endocarditis, peritonitis and many other serious...
is an opportunistic pathogen, particularly life-threatening for the immunocompromised. It is associated with pneumonia, endocarditis, peritonitis and many other serious infections, including septicemia. Of note, produces metabolites that support and increase overgrowth of , one of the ESKAPE bacteria. Endolysins are considered as antibacterial enzymes derived from bacteriophages that selectively and efficiently kill susceptible bacteria without harming human cells or the normal microbiome. Here, we applied a computational analysis of metagenomic sequencing data of the gastric mucosa phageome extracted from human patients' stomach biopsies. A selected candidate anti- sequence was produced in an expression system, purified and confirmed as a - and -specific endolysin PolaR, able to destroy bacterial cells even when aggregated, as in a biofilm. PolaR had no cytotoxic or antiproliferative effects on mammalian cells. PolaR is the first described endolysin selectively targeting species, with a high potential to combat infections caused by and , and possibly other bacterial groups. PolaR is the first antibacterial enzyme selected from the gastric mucosa phageome, which underlines the biological complexity and probably underestimated biological role of the phageome in the human gastric mucosa.
Topics: Animals; Humans; Bacteriophages; Micrococcaceae; Bacteria; Anti-Bacterial Agents; Mammals
PubMed: 37566076
DOI: 10.3390/cells12151997 -
PloS One 2023New evidence strongly discloses the pathogenesis of host-associated microbiomes in respiratory diseases. The microbiome dysbiosis modulates the lung's behavior and...
New evidence strongly discloses the pathogenesis of host-associated microbiomes in respiratory diseases. The microbiome dysbiosis modulates the lung's behavior and deteriorates the respiratory system's effective functioning. Several exogenous and environmental factors influence the development of asthma and chronic lung disease. The relationship between asthma and microbes is reasonably understood and yet to be investigated for more substantiation. The comorbidities such as SARS-CoV-2 further exacerbate the health condition of the asthma-affected individuals. This study examines the raw 16S rRNA sequencing data collected from the saliva and nasopharyngeal regions of pre-existing asthma (23) and non-asthma patients (82) infected by SARS-CoV-2 acquired from the public database. The experiment is designed in a two-fold pattern, analyzing the associativity between the samples collected from the saliva and nasopharyngeal regions. Later, investigates the microbial pathogenesis, its role in exacerbations of respiratory disease, and deciphering the diagnostic biomarkers of the target condition. LEfSE analysis identified that Actinobacteriota and Pseudomonadota are enriched in the SARS-CoV-2-non-asthma group and SARS-CoV-2 asthma group of the salivary microbiome, respectively. Random forest algorithm is trained with amplicon sequence variants (ASVs) attained better classification accuracy, ROC scores on nasal (84% and 87%) and saliva datasets (93% and 97.5%). Rothia mucilaginosa is less abundant, and Corynebacterium tuberculostearicum showed higher abundance in the SARS-CoV-2 asthma group. The increase in Streptococcus at the genus level in the SARS-CoV-2-asthma group is evidence of discriminating the subgroups.
Topics: Humans; SARS-CoV-2; RNA, Ribosomal, 16S; COVID-19; Asthma; Nose; Microbiota; Lung
PubMed: 37590197
DOI: 10.1371/journal.pone.0289891 -
Skin Research and Technology : Official... Sep 2023Skin microorganisms co-develop with the human body and age influences the skin microenvironment and thus the skin bacterial community.
BACKGROUND
Skin microorganisms co-develop with the human body and age influences the skin microenvironment and thus the skin bacterial community.
OBJECTIVES
To investigate the changes in the skin microbiota during male development.
METHODS
High-throughput 16S ribosomal RNA pyrosequencing was utilized to analyze the differences in bacterial composition of the skin in healthy males aged 0-25 years.
RESULTS
There were significant differences in facial skin bacterial diversity (Shannon index) and richness (Chao index) among the 4 groups of subjects (p < 0.05). Streptococcus, Staphylococcus, Cutibacterium are dominant in males during growth, and regular changes occur with age after birth. Further analysis of skin bacteria between the 4 groups showed that the bacterial abundance of Cutibacterium acnes and Staphylococcus epidermidis tended to increase with age, and the bacterial abundance of Streptococcus, Rothia mucilaginosa, and Staphylococcus hominis tended to decrease with age.
CONCLUSIONS
There are some changes in cheek skin bacterial diversity during male development, and there is a relationship between skin bacterial changes and skin development processes.
Topics: Humans; Male; Infant, Newborn; Infant; Child, Preschool; Child; Adolescent; Young Adult; Adult; Skin; Microbiota; Staphylococcus hominis
PubMed: 37753696
DOI: 10.1111/srt.13432 -
Journal of Oral Microbiology 2023We investigated bacterial colonisation patterns of healthy mucosa (buccal, tongue, palate and floor of mouth) in a cohort of adults in order to determine how smoking,...
We investigated bacterial colonisation patterns of healthy mucosa (buccal, tongue, palate and floor of mouth) in a cohort of adults in order to determine how smoking, tooth loss, plaque levels and oral hygiene practices impacted on mucosal colonisation. A total of 322 swabs were recovered from 256 participants, of whom 46% were current smokers. We analysed colonization by sequencing the V1-V3 regions of the 16S rRNA gene. Palate and tongue microbiomes generally exhibited greater biodiversity than buccal and floor of mouth. Although , and spp. showed reduced abundance in smokers, buccal mucosa specifically showed a significant increase in spp., whereas tongue and floor of mouth tended towards increased abundance of spp. Unexpectedly, tooth brushing frequency had a greater impact on mucosal community structure than plaque levels. Tooth loss was associated with significant reductions in mucosal biodiversity and had site-specific impacts, with buccal communities showing increased abundance of periodontitis-associated species and , whereas tongue communities exhibited increased abundance of several streptococcal OTUs and reduced abundance of spp. This study highlights the complex relationship between mucosal colonisation and host factors, highlighting the need for careful consideration of these factors in mucosal microbiome studies.
PubMed: 37795170
DOI: 10.1080/20002297.2023.2263971 -
BMC Pulmonary Medicine Jun 2024Community-acquired pneumonia (CAP) patients with chronic obstructive pulmonary disease (COPD) have higher disease severity and mortality compared to those without COPD....
Exploring the microbiota difference of bronchoalveolar lavage fluid between community-acquired pneumonia with or without COPD based on metagenomic sequencing: a retrospective study.
BACKGROUND
Community-acquired pneumonia (CAP) patients with chronic obstructive pulmonary disease (COPD) have higher disease severity and mortality compared to those without COPD. However, deep investigation into microbiome distribution of lower respiratory tract of CAP with or without COPD was unknown.
METHODS
So we used metagenomic next generation sequencing (mNGS) to explore the microbiome differences between the two groups.
RESULTS
Thirty-six CAP without COPD and 11 CAP with COPD cases were retrieved. Bronchoalveolar lavage fluid (BALF) was collected and analyzed using untargeted mNGS and bioinformatic analysis. mNGS revealed that CAP with COPD group was abundant with Streptococcus, Prevotella, Bordetella at genus level and Cutibacterium acnes, Rothia mucilaginosa, Bordetella genomosp. 6 at species level. While CAP without COPD group was abundant with Ralstonia, Prevotella, Streptococcus at genus level and Ralstonia pickettii, Rothia mucilaginosa, Prevotella melaninogenica at species level. Meanwhile, both alpha and beta microbiome diversity was similar between groups. Linear discriminant analysis found that pa-raburkholderia, corynebacterium tuberculostearicum and staphylococcus hominis were more enriched in CAP without COPD group while the abundance of streptococcus intermedius, streptococcus constellatus, streptococcus milleri, fusarium was higher in CAP with COPD group.
CONCLUSIONS
These findings revealed that concomitant COPD have an mild impact on lower airway microbiome of CAP patients.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Bronchoalveolar Lavage Fluid; Community-Acquired Infections; Male; Retrospective Studies; Aged; Female; Microbiota; Middle Aged; Metagenomics; High-Throughput Nucleotide Sequencing; Pneumonia; Aged, 80 and over
PubMed: 38867204
DOI: 10.1186/s12890-024-03087-6 -
PLoS Computational Biology Jul 2023The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in millions of deaths worldwide. The disease presents with various manifestations that can vary in...
The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in millions of deaths worldwide. The disease presents with various manifestations that can vary in severity and long-term outcomes. Previous efforts have contributed to the development of effective strategies for treatment and prevention by uncovering the mechanism of viral infection. We now know all the direct protein-protein interactions that occur during the lifecycle of SARS-CoV-2 infection, but it is critical to move beyond these known interactions to a comprehensive understanding of the "full interactome" of SARS-CoV-2 infection, which incorporates human microRNAs (miRNAs), additional human protein-coding genes, and exogenous microbes. Potentially, this will help in developing new drugs to treat COVID-19, differentiating the nuances of long COVID, and identifying histopathological signatures in SARS-CoV-2-infected organs. To construct the full interactome, we developed a statistical modeling approach called MLCrosstalk (multiple-layer crosstalk) based on latent Dirichlet allocation. MLCrosstalk integrates data from multiple sources, including microbes, human protein-coding genes, miRNAs, and human protein-protein interactions. It constructs "topics" that group SARS-CoV-2 with genes and microbes based on similar patterns of co-occurrence across patient samples. We use these topics to infer linkages between SARS-CoV-2 and protein-coding genes, miRNAs, and microbes. We then refine these initial linkages using network propagation to contextualize them within a larger framework of network and pathway structures. Using MLCrosstalk, we identified genes in the IL1-processing and VEGFA-VEGFR2 pathways that are linked to SARS-CoV-2. We also found that Rothia mucilaginosa and Prevotella melaninogenica are positively and negatively correlated with SARS-CoV-2 abundance, a finding corroborated by analysis of single-cell sequencing data.
Topics: Humans; SARS-CoV-2; COVID-19; Post-Acute COVID-19 Syndrome; Pandemics; MicroRNAs
PubMed: 37410793
DOI: 10.1371/journal.pcbi.1011222 -
International Journal of Infectious... May 2024Non-tuberculous mycobacteria (NTM) frequently colonize the airways of patients with bronchiectasis; however, there has been limited research into airway microbiota...
OBJECTIVES
Non-tuberculous mycobacteria (NTM) frequently colonize the airways of patients with bronchiectasis; however, there has been limited research into airway microbiota composition and predisposing factors for NTM detection during acute bronchiectasis exacerbations.
METHODS
This study enrolled 34 patients with bronchiectasis experiencing acute exacerbations. Metagenomic next-generation sequencing was used to detect microbiota in bronchoalveolar lavage fluid (BALF), and bioinformatics methods were used for the comparative analysis of meaningful microbiota in the BALF of patients with acute exacerbations of bronchiectasis. A correlation analysis was conducted to identify susceptibility factors for NTM in patients with bronchiectasis.
RESULTS
Compared with patients with community-acquired pneumonia, patients with bronchiectasis had higher detection rates of NTM (38.2%), Pseudomonas aeruginosa, and Haemophilus influenzae. Patients with NTM-positive bronchiectasis had lower body mass index and lipid profiles than patients who were NTM-negative. Metagenomic next-generation sequencing of BALF revealed patients who were NTM-positive had increased relative abundance of Rothia and other anaerobic genera compared with patients who were NTM-negative. Patients who were NTM-positive also showed higher levels of Streptococcus parasanguinis at the species level. Elevated Rothia mucilaginosa and S. parasanguinis correlated with decreased percentages of clusters of differentiation 3+ T lymphocytes and clusters of differentiation 3+ T-cell subgroups in peripheral blood.
CONCLUSIONS
NTM colonization increases the risk of acute bronchiectasis exacerbations. Low body mass index, lipid levels, and isolation of R. mucilaginosa and S. parasanguinis in BALF are susceptibility factors for NTM colonization in patients with bronchiectasis.
PubMed: 38821186
DOI: 10.1016/j.ijid.2024.107120 -
Biomedical Reports Jun 2024Phototherapy is the most commonly used treatment for neonatal hyperbilirubinemia (NH). Gut microbiota is involved in bilirubin metabolism; however, it is uncertain...
Phototherapy is the most commonly used treatment for neonatal hyperbilirubinemia (NH). Gut microbiota is involved in bilirubin metabolism; however, it is uncertain whether this is affected by phototherapy. The present study included 43 newborns with hyperbilirubinemia and collected fecal samples for high-throughput sequencing before and after phototherapy. Selection α diversity analysis was used to determine the differences in diversity and abundance between the two groups, whereas similarity was determined using β diversity analysis. Linear discriminant analysis effect size analysis was used to screen for markedly different bacteria. The structure of the gut microbiota in newborns with hyperbilirubinemia changed after phototherapy, with a significant decrease in abundance and diversity. The changes in the key bacterial species were characterized by an increase in the abundance of and a decrease in the abundance of , , and . These changes mainly manifested as an increase in beneficial bacteria and a decrease in opportunistic bacteria, which may not be related to the side effects of phototherapy. These results can provide theoretical assistance for microbiological research on the later stages of NH.
PubMed: 38765854
DOI: 10.3892/br.2024.1789