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Respiratory Research Nov 2023The prevalence and clinical correlates of antibiotic resistance genes (ARGs) in bronchiectasis are not entirely clear. We aimed to profile the ARGs in sputum from adults...
The prevalence and clinical correlates of antibiotic resistance genes (ARGs) in bronchiectasis are not entirely clear. We aimed to profile the ARGs in sputum from adults with bronchiectasis, and explore the association with airway microbiome and disease severity and subtypes. In this longitudinal study, we prospectively collected 118 sputum samples from stable and exacerbation visits of 82 bronchiectasis patients and 19 healthy subjects. We profiled ARGs with shotgun metagenomic sequencing, and linked these to sputum microbiome and clinical characteristics, followed by validation in an international cohort. We compared ARG profiles in bronchiectasis according to disease severity, blood and sputum inflammatory subtypes. Unsupervised clustering revealed a Pseudomonas predominant subgroup (n = 16), Haemophilus predominant subgroup (n = 48), and balanced microbiome subgroup (N = 54). ARGs of multi-drug resistance were over-dominant in the Pseudomonas-predominant subgroup, while ARGs of beta-lactam resistance were most abundant in the Haemophilus-predominant subgroup. Pseudomonas-predominant subgroup yielded the highest ARG diversity and total abundance, while Haemophilus-predominant subgroup and balanced microbiota subgroup were lowest in ARG diversity and total abundance. PBP-1A, ksgA and emrB (multidrug) were most significantly enriched in Haemophilus-predominant subtype. ARGs generally correlated positively with Bronchiectasis Severity Index, fluoroquinolone use, and modified Reiff score. 68.6% of the ARG-clinical correlations could be validated in an independent international cohort. In conclusion, ARGs are differentially associated with the dominant microbiome and clinical characteristics in bronchiectasis.
Topics: Adult; Humans; Haemophilus; Pseudomonas; Longitudinal Studies; Bronchiectasis; Respiratory System; Anti-Bacterial Agents
PubMed: 37919749
DOI: 10.1186/s12931-023-02562-8 -
Heliyon Feb 2024Autoimmune thyroiditis (AIT), also known as Hashimoto's thyroiditis (HT) or chronic lymphocytic thyroiditis, is a prevalent autoimmune disorder. Despite its high...
BACKGROUND
Autoimmune thyroiditis (AIT), also known as Hashimoto's thyroiditis (HT) or chronic lymphocytic thyroiditis, is a prevalent autoimmune disorder. Despite its high prevalence, the pathogenesis of AIT remains unclear. Previous studies have suggested a potential association between gut microbiota and AIT. However, whether this relationship is causal or coincidental remains uncertain. To address this gap in knowledge, our study aimed to investigate the potential causal association between gut microbiota and AIT using the two-sample Mendelian randomization (MR) method.
METHODS
Summary-level gut microbiota data comprising 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla) were obtained from the comprehensive MiBioGen study. Genetic associations with 22 gastrointestinal diseases were extracted from the UK Biobank, FinnGen study, and various extensive GWAS studies. A meticulous MR analysis was conducted to evaluate the causal relationship between genetically predicted gut microbiota and these gastrointestinal diseases. Sensitivity analyses and tests for heterogeneity were systematically performed to validate the reliability of our findings.
RESULTS
Six gut microbiota species showed significant associations with AIT according to the IVW method. Among them, the following exhibited negative associations with AIT: family Alcaligenaceae, family Pasteurellaceae (ID: 3689), family Peptococcaceae, genus Lachnospira, genus Victivallis, and order Pasteurellales (ID: 3688). No evidence of pleiotropy or heterogeneity was detected.
CONCLUSION
The MR analysis uncovered a causal relationship at the genetic prediction level between specific gut microbiota and AIT. These findings offer novel insights into the mechanisms governing the development of AIT mediated by gut microbiota. This knowledge could inform the design of future interventions, potentially involving microbiome-related strategies, to address the mechanisms associated with AIT development.
PubMed: 38356548
DOI: 10.1016/j.heliyon.2024.e25652 -
Microbial Pathogenesis Nov 2023Pasteurella multocida.(PM) infection is a major cause of avian cholera, but the pathogenesis of the disease is unknown. The purpose of this study was to further... (Review)
Review
Pasteurella multocida.(PM) infection is a major cause of avian cholera, but the pathogenesis of the disease is unknown. The purpose of this study was to further understand the host response to infection by using a duck model of PM, 20 female ducks were divided into two groups (n = 10). One group was infected with PM, while the other served as an uninfected control group. The ducks were observed after infection and samples were collected for testing. In this study, we report the mechanism of PM-induced inflammation to further mediate apoptosis and autophagic signaling pathways in liver cells. Our results demonstrated that PM infection initially induces hemorrhagic and necrotic lesions in the liver tissue of duck, promoting inflammasome assembly and release, triggering inflammation. The TLR4/NF-κB axis activated and interacted with multiple inflammation-related proteins, including TNF-α and IL-1β, which affected apoptosis and autophagy. Tumor necrosis factor induced hepatocyte apoptosis was implicated in a wide range of liver diseases; the release of TNF-α and activation with NF-κB further incite apoptotic pathways,such as Bax/BCL2/caspase to promote apoptotic genes APAF1, Bax, Caspase3, BCL-2, p53, and Cytc expression. Finally, PM-induced autophagy suppressed liver injury by promoting the Beclin-1, LC3B, p62, and mTOR. Thus, liver injury caused by PM via promoting autophagy was induced. In conclusion, we analyzed the liver injury of ducks infected with PM, and confirmed that inflammation appeared in the liver; this was followed by the intricate interplay between inflammation, apoptosis, and autophagy signaling pathways. The observed results provided a reference basis for studying pathogenic mechanisms of PM-host interactions.
Topics: Animals; Female; Pasteurella multocida; Ducks; NF-kappa B; Tumor Necrosis Factor-alpha; bcl-2-Associated X Protein; Liver; Inflammation; Autophagy; Apoptosis
PubMed: 37683832
DOI: 10.1016/j.micpath.2023.106336 -
Clinical Otolaryngology : Official... Sep 2023Acute otitis media (AOM) and otitis externa (OE) are common ear infections which may warrant antibiotic therapy. For many infections, there is a rise in antimicrobial...
OBJECTIVES
Acute otitis media (AOM) and otitis externa (OE) are common ear infections which may warrant antibiotic therapy. For many infections, there is a rise in antimicrobial resistance, which is associated with treatment failure, morbidity, prolonged hospitalisation and mortality. This study aimed to identify longitudinal changes in microbiology and antimicrobial resistance in aural swabs taken from patients with AOM or OE.
DESIGN
Retrospective observational analysis.
SETTING
Aural samples processed at Manchester Medical Microbiology Partnership Laboratories between January 2008 and December 2018 were analysed to record organism isolated and antimicrobial sensitivity.
PARTICIPANTS
Individual aural swabs from 7200 patients.
MAIN OUTCOME MEASURES
Changes in the incidence of organisms and antimicrobial resistance between two time periods (2008-2012 and 2013-2018) were compared using the chi-squared test (alpha = 0.05).
RESULTS
From 7200 swabs, 2879 (40%) were from children. The most frequently isolated organisms were Staphylococcus aureus (25%), Pseudomonas aeruginosa (24.4%), yeast (9.1%), mixed anaerobes (7.9%) and Haemophilus influenzae (6.1%). In children aged 0-4 years, H. influenzae had particularly high incidence (25%). Overall, the incidence of P. aeruginosa decreased significantly with time (p = 0.05). Isolates displaying resistance to one or more antimicrobial agents increased significantly in number in the second time period for P. aeruginosa (p = 0.04) and H. influenzae (p = 0.03). There was increased resistance to amoxicillin for P. aeruginosa (p = 0.01) and to erythromycin for H. influenzae (p < 0.01).
CONCLUSION
Variations in type and frequency of organisms with increasing age likely result from differences in the preponderance of AOM compared to OE in children versus adults. We found increasing antimicrobial resistance for two organisms commonly isolated from AOM and OE infections, suggesting that aspects of current UK treatment practices and national recommendations may need to be revised.
Topics: Adult; Child; Humans; Otitis Externa; Anti-Bacterial Agents; Retrospective Studies; Drug Resistance, Bacterial; Otitis Media; Haemophilus influenzae
PubMed: 37183531
DOI: 10.1111/coa.14071 -
Carbohydrate Research Dec 2023N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus...
N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides. Here, we expressed and characterized a novel N-glycosyltransferase from Mannheimia haemolytica (named MhNGT). RP-HPLC and Mass Spectrometry were used to assay and quantify glycopeptide formation by MhNGT and determine its substrate specificities. MhNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal and UDP-Xyl, to glycosylate the tested peptides DANYTK, GGNWTT and PAVGNCSSALR with higher efficiency than ApNGT which was comprehensive studied. The optimum temperature of MhNGT was about 30 °C and the optimum pH was 7.5-8.0 in PBS-NaOH buffer. MhNGT exhibited a different position-specific residue preference of substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT). The effective glycosylation of common short peptides by MhNGT demonstrated the enzyme's potential to alter therapeutically significant mammalian N-glycoproteins.
Topics: Animals; Mannheimia haemolytica; Glycosyltransferases; Peptides; Protein Isoforms; Uridine Diphosphate; Mammals
PubMed: 37783053
DOI: 10.1016/j.carres.2023.108947 -
Frontiers in Microbiology 2023The present study was undertaken to address the recent spate of pasteurellosis outbreaks among sea-farmed Atlantic salmon () in Norway and Scotland, coinciding with...
The present study was undertaken to address the recent spate of pasteurellosis outbreaks among sea-farmed Atlantic salmon () in Norway and Scotland, coinciding with sporadic disease episodes in lumpfish () used for delousing purposes in salmon farms. Genome assemblies from 86 bacterial isolates cultured from diseased salmon or lumpfish confirmed them all as members of the family, with phylogenetic reconstruction dividing them into two distinct branches sharing <88% average nucleotide identity. These branches therefore constitute two separate species, namely and the as-yet invalidly named "". Both species further stratify into multiple discrete genomovars (gv.) and/or lineages, each being nearly or fully exclusive to a particular host, geographic region, and/or time period. Pasteurellosis in lumpfish is, irrespective of spatiotemporal origin, linked almost exclusively to the highly conserved " gv. " (Pac). In contrast, pasteurellosis in Norwegian sea-farmed salmon, dominated since the late-1980s by " gv. " (Pas), first saw three specific lineages (Pas-1, -2, and -3) causing separate, geographically restricted, and short-lived outbreaks, before a fourth (Pas-4) emerged recently and became more widely disseminated. A similar situation involving (Ps) has apparently been unfolding in Scottish salmon farming since the mid-1990s, where two historic (Ps-1 and -2) and one contemporary (Ps-3) lineages have been recorded. While the epidemiology underlying all these outbreaks/epizootics remains unclear, repeated detection of 16S rRNA gene amplicons very closely related to and "" from at least five cetacean species worldwide raises the question as to whether marine mammals may play a part, possibly as reservoirs. In fact, the close relationship between the studied isolates and associated with harbor porpoise (), and their relatively distant relationship with other members of the genus , suggests that both and "" should be moved to the genus .
PubMed: 37808299
DOI: 10.3389/fmicb.2023.1236290 -
Thoracic Cancer Apr 2024The causal relationship between breast cancer (BC) and the oral microbiome remains unclear. In this case-control study, using two-sample Mendelian randomization (MR), we...
BACKGROUND
The causal relationship between breast cancer (BC) and the oral microbiome remains unclear. In this case-control study, using two-sample Mendelian randomization (MR), we thoroughly explored the relationship between the oral microbiome and BC in the East Asian population.
METHODS
Genetic summary data related to oral microbiota and BC were collected from genome-wide association studies involving participants of East Asian descent. MR estimates were generated by conducting various analyses. Sequencing data from a case-control study were used to verify the validity of these findings.
RESULTS
MR analysis revealed that 30 tongue and 37 salivary bacterial species were significantly associated with BC. Interestingly, in both tongue and salivary microbiomes, we observed the causal effect of six genera, namely, Aggregatibacter, Streptococcus, Prevotella, Haemophilus, Lachnospiraceae, Oribacterium, and Solobacterium, on BC. Our case-control study findings suggest differences in specific bacteria between patients with BC and healthy controls. Moreover, sequencing data confirmed the MR analysis results, demonstrating that compared with the healthy control group, the BC group had a higher relative abundance of Pasteurellaceae and Streptococcaceae but a lower relative abundance of Bacteroidaceae.
CONCLUSIONS
Our MR analysis suggests that the oral microbiome exerts a causative effect on BC risk, supported by the sequencing data of a case-control study. In the future, studies should be undertaken to comprehensively understand the complex interaction mechanisms between the oral microbiota and BC.
Topics: Female; Humans; Breast Neoplasms; Case-Control Studies; East Asian People; Genome-Wide Association Study; Mendelian Randomization Analysis; Microbiota; Mouth
PubMed: 38485288
DOI: 10.1111/1759-7714.15280 -
Veterinary Microbiology Aug 2023Amongst the bacterial pathogens associated with the bovine respiratory disease syndrome (BRD) in cattle are Mannheimia haemolytica and Mycoplasma bovis. The interaction...
Amongst the bacterial pathogens associated with the bovine respiratory disease syndrome (BRD) in cattle are Mannheimia haemolytica and Mycoplasma bovis. The interaction between these two pathogens has not been investigated before; thus, there are gaps in the knowledge of why and how a previous infection with M. haemolytica allows the development of M. bovis-related lesions. We hypothesized that upon M. haemolytica infection, inflammatory products are produced in the lung and that these inflammatory products stimulate M. bovis to produce proteases and lipases that degrade lipids and proteins important for lung function. In this work, we identified several M. bovis proteases and lipases whose expression was modulated by M. haemolytica products in vitro. We performed co-infection animal challenges to develop a model to test vaccine protection. A prior exposure to BHV-1 followed by infection with M. bovis and M. haemolytica resulted in severe pathology and the BHV-1 infection was abandoned. When M. bovis and M. haemolytica were introduced into the lungs by bronchoscopy, we found that M. haemolytica resulted in worsening of the respiratory disease caused by M. bovis. We performed a proof-of-concept trial where animals were immunized with the M. bovis proteins identified in this study and challenged with both pathogens. Despite detecting significant humoral immune responses to the antigens, the experimental vaccine failed to protect against M. bovis disease.
Topics: Animals; Cattle; Bacteria; Cattle Diseases; Mannheimia haemolytica; Mycoplasma bovis; Respiratory Tract Diseases; Proof of Concept Study
PubMed: 37276814
DOI: 10.1016/j.vetmic.2023.109793 -
Genome Jan 2024causes acute/chronic pasteurellosis in porcine, resulting in considerable economic losses globally. The draft genomes of two Indian strains NIVEDIPm17 (serogroup D) and...
causes acute/chronic pasteurellosis in porcine, resulting in considerable economic losses globally. The draft genomes of two Indian strains NIVEDIPm17 (serogroup D) and NIVEDIPm36 (serogroup A) were sequenced. A total of 2182-2284 coding sequences (CDSs) were predicted along with 5-6 rRNA and 45-46 tRNA genes in the genomes. Multilocus sequence analysis and LPS genotyping showed the presence of ST50: genotype 07 and ST74: genotype 06 in NIVEDIPm17 and NIVEDIPm36, respectively. Pangenome analysis of 61 strains showed the presence of 1653 core genes, 167 soft core genes, 750 shell genes, and 1820 cloud genes. Analysis of virulence-associated genes in 61 genomes indicated the presence of , and in all strains. The 61 genomes contained genes encoding tetracycline (54%), streptomycin (48%), sulphonamide (28%), tigecycline (25%), chloramphenicol (21%), amikacin (7%), cephalosporin (5%), and trimethoprim (5%) resistance. Multilocus sequence type revealed that ST50 was the most common (34%), followed by ST74 (26%), ST13 (24%), ST287 (5%), ST09 (5%), ST122 (3%), and ST07 (2%). Single-nucleotide polymorphism and core genome-based phylogenetic analysis clustered the strains into three major clusters. In conclusion, we described the various virulence factors, mobile genetic elements, and antimicrobial resistance genes in the pangenome of of porcine origin, besides the rare presence of LPS genotype 7 in serogroup D.
Topics: Animals; Swine; Pasteurella multocida; Phylogeny; Lipopolysaccharides; Pasteurella Infections; Virulence Factors
PubMed: 37639729
DOI: 10.1139/gen-2023-0021 -
Pharmacological Research Jun 2024Studies have shown that the microbiota-gut-brain axis is highly correlated with the pathogenesis of depression in humans. However, whether independent oral microbiome...
Studies have shown that the microbiota-gut-brain axis is highly correlated with the pathogenesis of depression in humans. However, whether independent oral microbiome that do not depend on gut microbes could affect the progression of depression in human beings remains unclear, neither does the presence and underlying mechanisms of the microbiota-oral-brain axis in the development of the condition. Hence this study that encompasses clinical and animal experiments aims at investigating the correlation between oral microbiota and the onset of depression via mediating the microbiota-oral-brain axis. We compared the oral microbial compositions and metabolomes of 87 patients with depressive symptoms versus 70 healthy controls. We found that the oral microbial and metabolic signatures were significantly different between the two groups. Significantly, germ-free (GF) mice transplanted with saliva from mice exposing to chronic restraint stress (CRS) displayed depression-like behavior and oral microbial dysbiosis. This was characterized by a significant differential abundance of bacterial species, including the enrichment of Pseudomonas, Pasteurellaceae, and Muribacter, as well as the depletion of Streptococcus. Metabolomic analysis showed the alternation of metabolites in the plasma of CRS-exposed GF mice, especially Eicosapentaenoic Acid. Furthermore, oral and gut barrier dysfunction caused by CRS-induced oral microbiota dysbiosis may be associated with increased blood-brain barrier permeability. Pseudomonas aeruginosa supplementation exacerbated depression-like behavior, while Eicosapentaenoic Acid treatment conferred protection against depression-like states in mice. These results suggest that oral microbiome and metabolic function dysbiosis may be relevant to the pathogenesis and pathophysiology of depression. The proposed microbiota-oral-brain axis provides a new way and targets for us to study the pathogenesis of depression.
Topics: Animals; Dysbiosis; Depression; Male; Humans; Stress, Psychological; Female; Adult; Mice; Restraint, Physical; Mice, Inbred C57BL; Gastrointestinal Microbiome; Brain-Gut Axis; Mouth; Middle Aged; Saliva; Behavior, Animal; Blood-Brain Barrier
PubMed: 38763328
DOI: 10.1016/j.phrs.2024.107214