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Respiratory Research Jun 2019Little is known about the interactions between the lung microbiome and host response in chronic obstructive pulmonary disease (COPD).
BACKGROUND
Little is known about the interactions between the lung microbiome and host response in chronic obstructive pulmonary disease (COPD).
METHODS
We performed a longitudinal 16S ribosomal RNA gene-based microbiome survey on 101 sputum samples from 16 healthy subjects and 43 COPD patients, along with characterization of host sputum transcriptome and proteome in COPD patients.
RESULTS
Dysbiosis of sputum microbiome was observed with significantly increased relative abundance of Moraxella in COPD versus healthy subjects and during COPD exacerbations, and Haemophilus in COPD ex-smokers versus current smokers. Multivariate modeling on sputum microbiome, host transcriptome and proteome profiles revealed that significant associations between Moraxella and Haemophilus, host interferon and pro-inflammatory signaling pathways and neutrophilic inflammation predominated among airway host-microbiome interactions in COPD. While neutrophilia was positively correlated with Haemophilus, interferon signaling was more strongly linked to Moraxella. Moreover, while Haemophilus was significantly associated with host factors both in stable state and during exacerbations, Moraxella-associated host responses were primarily related to exacerbations.
CONCLUSIONS
Our study highlights a significant airway host-microbiome interplay associated with COPD inflammation and exacerbations. These findings indicate that Haemophilus and Moraxella influence different components of host immune response in COPD, and that novel therapeutic strategies should consider targeting these bacteria and their associated host pathways in COPD.
Topics: Aged; Female; Gene Expression Profiling; Haemophilus influenzae; Host Microbial Interactions; Humans; Longitudinal Studies; Lung; Male; Microbiota; Middle Aged; Moraxella; Pulmonary Disease, Chronic Obstructive; Sputum
PubMed: 31170986
DOI: 10.1186/s12931-019-1085-z -
Virulence Dec 2024is a major cause of chronic obstructive pulmonary disease. Toll-like receptor 2 (TLR2) plays an important role in the inflammatory response in host respiratory...
is a major cause of chronic obstructive pulmonary disease. Toll-like receptor 2 (TLR2) plays an important role in the inflammatory response in host respiratory epithelial cells. induces an inflammatory immune response in respiratory epithelial cells that is mostly dependent on TLR2. However, the mechanisms by which this pathogen adheres to and invades the respiratory epithelium are not well understood. The present study aimed to reveal the role of TLR2 in adhesion to and invasion into alveolar epithelial cells, using molecular techniques. Pretreatment with the TLR2 inhibitor TLR2-IN-C29 enhanced adhesion to A549 cells but reduced its invasion, whereas the agonist Pam3CSK4 reduced both adhesion and invasion into A549 cells. Similarly, 73-OR strain adhesion and invasion were significantly reduced in TLR2 A549 cells. Moreover, the lung clearance rate of the 73-OR strain was significantly higher in TLR2 C57/BL6J mice than in wild-type (WT) mice. Histological analysis showed that inflammatory responses were milder in TLR2 C57/BL6J mice than in WT mice, which was confirmed by a decrease in cytokine levels in TLR2 C57/BL6J mice. Overall, these results indicate that TLR2 promoted adhesion and invasion of A549 cells and lung tissues and mediated inflammatory responses in infected lungs. This study provides important insights into the development of potential therapeutic strategies against and TLR2-induced inflammatory responses.
Topics: Animals; Mice; Alveolar Epithelial Cells; Epithelial Cells; Lung; Moraxella catarrhalis; Toll-Like Receptor 2
PubMed: 38169345
DOI: 10.1080/21505594.2023.2298548 -
Vaccine Dec 2008The microbiology of acute otitis media (AOM) is linked to the nasopharyngeal commensal flora. This respiratory ecosystem undergoes various selective pressures, such as... (Review)
Review
The microbiology of acute otitis media (AOM) is linked to the nasopharyngeal commensal flora. This respiratory ecosystem undergoes various selective pressures, such as antibiotic consumption and vaccine use. Socio-economic conditions also influence the bacterial composition of the nasopharynx. Streptococcus pneumoniae, non-encapsulated Haemophilus influenzae, Moraxella catarrhalis, and group A Streptococcus are the leading causes of bacterial AOM worldwide. This paper will discuss the causes and consequences of recent shifts in the underlying microbiology of AOM.
Topics: Acute Disease; Bacterial Infections; Child, Preschool; Haemophilus influenzae; Humans; Incidence; Infant; Moraxella catarrhalis; Nasopharynx; Otitis Media; Streptococcus pneumoniae; Streptococcus pyogenes
PubMed: 19094935
DOI: 10.1016/j.vaccine.2008.11.006 -
Carbohydrate Research Feb 2024Moraxella ovis is a Gram-negative bacterium isolated from sheep conjunctivitis cases and is a rare isolate of infectious bovine keratoconjunctivitis (IBK). This species...
Moraxella ovis is a Gram-negative bacterium isolated from sheep conjunctivitis cases and is a rare isolate of infectious bovine keratoconjunctivitis (IBK). This species is closely related to M. bovoculi, another species which can also be isolated from IBK, or cattle upper respiratory tract (URT). Prior to molecular identification techniques, M. bovoculi was frequently misclassified as M. ovis. We previously described the structure of two oligosaccharides (lipooligosaccharide-derived, minor and major glycoforms) from M. bovoculi 237T (type strain, also ATCC BAA-1259T). Here, we have identified the genetic loci for lipooligosaccharide synthesis in M. ovis 354T (NCTC11227) and compared it with M. bovoculi 237T. We identified genes encoding the known glycosyltransferases Lgt6 and Lgt3 in M.ovis. These genes are conserved in Moraxella spp., including M bovoculi. We identified three further putative OS biosynthesis genes that are restricted to M. ovis and M. bovoculi. These encode enzymes predicted to function as GDP-mannose synthases, namely a mannosyltransferase and a glycosyltransferase. Adding insight into the genetic relatedness of M.ovis and M. bovoculi, the M. ovis genes have higher similarity to those in M. bovoculi genotype 2 (nasopharyngeal isolates from asymptomatic cattle), than to M. bovoculi genotype 1 (isolates from eyes of IBK-affected cattle). Sequence analysis confirmed that the predicted mannosyltransferase in M. bovoculi 237T is interrupted by a C>T polymorphism. This mutation is not present in other M. bovoculi strains sequenced to date. We isolated and characterised LOS-derived oligosaccharide from M. ovis 354T. GLC-MS and NMR spectroscopy data revealed a heptasaccharide structure with three β-D-Glcp residues attached as branches to the central 3,4,6-α-D-Glcp, with subsequent attachment to Kdo. This inner core arrangement is consistent with the action of Lgt6 and Lgt3 glycosyltransferases. Two α-D-Manp residues are linearly attached to the 4-linked β-D-Glcp, consistent with the presence of the two identified glycosyltransferases. This oligosaccharide structure is consistent with the previously reported minor glycoform isolated from M. bovoculi 237T.
Topics: Animals; Cattle; Sheep; Mannosyltransferases; Keratoconjunctivitis, Infectious; Moraxella; Glycosyltransferases; Oligosaccharides; Lipopolysaccharides
PubMed: 38281396
DOI: 10.1016/j.carres.2024.109043 -
Brazilian Journal of Microbiology :... Sep 2021Infectious keratoconjunctivitis (IKC) is the most frequent ocular disease in livestock worldwide and is primarily caused by Moraxella bovis, M. ovis, and/or M. bovoculi....
Infectious keratoconjunctivitis (IKC) is the most frequent ocular disease in livestock worldwide and is primarily caused by Moraxella bovis, M. ovis, and/or M. bovoculi. The economic impact of IKC is mainly due to ocular damage, which leads to weight loss, management difficulties, pain and discomfort, and cost of treatments. In horses, limited information is available on the association of Moraxella spp. with keratoconjunctivitis. The present report describes two cases of equine keratoconjunctivitis caused by members of the genus Moraxella. Both animals presented with lacrimation, conjunctivitis, photophobia, mucoid or purulent secretions, blepharitis, and conjunctival hyperemia. The diagnosis of IKC was based on the epidemiological and clinical findings; the etiological agent was identified through bacteriological (culture and biochemistry assays) and molecular testing (PCR and nucleotide sequencing). Our study reports the isolation of Moraxella bovoculi (SBP 88/19) and a putative new species/mutant of Moraxella (SBP 39/19) recovered from ocular secretions in horses. Thus, we suggest the inclusion of Moraxella spp. infection in the differential diagnosis of conjunctivitis in horses in Southern Brazil.
Topics: Animals; Brazil; Horses; Keratoconjunctivitis, Infectious; Moraxella; Moraxellaceae Infections
PubMed: 33931826
DOI: 10.1007/s42770-021-00507-1 -
Scientific Reports Apr 2024Diabetes mellitus is recognized as a major predisposing factor for Moraxella keratitis. However, how diabetes mellitus contributes to Moraxella keratitis remains...
Diabetes mellitus is recognized as a major predisposing factor for Moraxella keratitis. However, how diabetes mellitus contributes to Moraxella keratitis remains unclear. In this study, we examined Moraxella keratitis; based on the findings, we investigated the impact of advanced glycation end products (AGEs) deposition in the cornea of individuals with diabetic mellitus on the adhesion of Moraxella isolates to the cornea. A retrospective analysis of 27 culture-proven cases of Moraxella keratitis at Ehime University Hospital (March 2006 to February 2022) was performed. Moraxella isolates were identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Among the patients, 30.4% had diabetes mellitus and 22.2% had the predominant ocular condition of using steroid eye drops. The species identified were Moraxella nonliquefaciens in 59.3% and Moraxella lacunata in 40.7% of patients. To investigate the underlying mechanisms, we assessed the effects of M. nonliquefaciens adherence to simian virus 40-immortalized human corneal epithelial cells (HCECs) with or without AGEs. The results demonstrated the number of M. nonliquefaciens adhering to HCECs was significantly increased by adding AGEs compared with that in controls (p < 0.01). Furthermore, in the corneas of streptozotocin-induced diabetic C57BL/6 mice treated with or without pyridoxamine, an AGE inhibitor, the number of M. nonliquefaciens adhering to the corneas of diabetic mice was significantly reduced by pyridoxamine treatment (p < 0.05). In conclusion, the development of Moraxella keratitis may be significantly influenced by the deposition of AGEs on the corneal epithelium of patients with diabetes mellitus.
Topics: Humans; Animals; Mice; Retrospective Studies; Diabetes Mellitus, Experimental; Pyridoxamine; Mice, Inbred C57BL; Keratitis; Moraxella; Cornea; Glycation End Products, Advanced
PubMed: 38580798
DOI: 10.1038/s41598-024-58659-7 -
Respiratory Research May 2022Non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) infections are frequently associated with exacerbations of chronic obstructive pulmonary... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and immunogenicity of three doses of non-typeable Haemophilus influenzae-Moraxella catarrhalis (NTHi-Mcat) vaccine when administered according to two different schedules: a phase 2, randomised, observer-blind study.
BACKGROUND
Non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) infections are frequently associated with exacerbations of chronic obstructive pulmonary disease (COPD). Results were reported with a two-dose (0-2 months) schedule of an investigational AS01-adjuvanted NTHi-Mcat vaccine containing three surface proteins from NTHi and one from Mcat. We evaluated the safety and immunogenicity of three NTHi-Mcat vaccine doses administered in two different schedules to adults with a smoking history (≥ 10 pack-years), immunologically representing the COPD population.
METHODS
In this 18-month, randomised (1:1), observer-blind study with 6-month open follow-up, 200 healthy adults aged 40-80 years received NTHi-Mcat vaccine at 0-2-6 months and placebo at 12 months (0-2-6 group), or vaccine at 0-2-12 months and placebo at 6 months (0-2-12 group). Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days, respectively, post-vaccination, and potential immune-mediated diseases (pIMDs) and serious AEs (SAEs) throughout the study. Immune responses were assessed.
RESULTS
No safety concerns were identified with the third vaccine dose or overall. Most solicited AEs were mild/moderate. Unsolicited AEs were reported in 16%, 16.1% and 14.4% of participants in the 0-2-6 group post-dose 1, 2 and 3, respectively, and 20%, 20.4% and 9.7%, respectively, in the 0-2-12 group. In 24 months, SAEs were reported in 12 participants in the 0-2-6 group and 9 in the 0-2-12 group (18 events in each group). There were three deaths (unknown cause, 0-2-6 group; myocardial infarction, lung cancer in 0-2-12 group). pIMDs were reported in three participants in the 0-2-6 group (non-serious inflammatory bowel disease, gout, psoriasis) and three in the 0-2-12 group (serious ulcerative colitis, two with non-serious gout). The SAEs, deaths and pIMDs were considered not causally related to vaccination. Antigen-specific antibody concentrations were higher at 12 months post-dose 1 with the 0-2-6 schedule than with the 0-2-12 schedule and at 12 months post-dose 3 were similar between schedules, remaining higher than baseline.
CONCLUSIONS
No safety concerns were identified when the investigational NTHi-Mcat vaccine was administered via a 0-2-6 months or 0-2-12 months schedule to older adults with a smoking history. Persistent immune responses were observed after the third vaccine dose. Trial registration https://clinicaltrials.gov/ ; NCT03443427, registered February 23, 2018.
Topics: Aged; Gout; Haemophilus influenzae; Humans; Moraxella catarrhalis; Pulmonary Disease, Chronic Obstructive; Vaccines
PubMed: 35509077
DOI: 10.1186/s12931-022-02019-4 -
Clinical Microbiology Reviews Jan 2002Moraxella catarrhalis (formerly known as Branhamella catarrhalis) has emerged as a significant bacterial pathogen of humans over the past two decades. During this... (Review)
Review
Moraxella catarrhalis (formerly known as Branhamella catarrhalis) has emerged as a significant bacterial pathogen of humans over the past two decades. During this period, microbiological and molecular diagnostic techniques have been developed and improved for M. catarrhalis, allowing the adequate determination and taxonomic positioning of this pathogen. Over the same period, studies have revealed its involvement in respiratory (e.g., sinusitis, otitis media, bronchitis, and pneumonia) and ocular infections in children and in laryngitis, bronchitis, and pneumonia in adults. The development of (molecular) epidemiological tools has enabled the national and international distribution of M. catarrhalis strains to be established, and has allowed the monitoring of nosocomial infections and the dynamics of carriage. Indeed, such monitoring has revealed an increasing number of B-lactamase-positive M. catarrhalis isolates (now well above 90%), underscoring the pathogenic potential of this organism. Although a number of putative M. catarrhalis virulence factors have been identified and described in detail, their relationship to actual bacterial adhesion, invasion, complement resistance, etc. (and ultimately their role in infection and immunity), has been established in a only few cases. In the past 10 years, various animal models for the study of M. catarrhalis pathogenicity have been described, although not all of these models are equally suitable for the study of human infection. Techniques involving the molecular manipulation of M. catarrhalis genes and antigens are also advancing our knowledge of the host response to and pathogenesis of this bacterial species in humans, as well as providing insights into possible vaccine candidates. This review aims to outline our current knowledge of M. catarrhalis, an organism that has evolved from an emerging to a well-established human pathogen.
Topics: Adult; Carbohydrate Sequence; Cell Wall; Child; Communicable Diseases, Emerging; Humans; Lipopolysaccharides; Molecular Sequence Data; Moraxella catarrhalis; Neisseriaceae Infections
PubMed: 11781271
DOI: 10.1128/CMR.15.1.125-144.2002 -
BMJ Open Respiratory Research Aug 2023Use of inhaled corticosteroids (ICS) is common in patients with chronic obstructive pulmonary disease (COPD) and has been associated with an increased risk of pneumonia.... (Observational Study)
Observational Study
BACKGROUND
Use of inhaled corticosteroids (ICS) is common in patients with chronic obstructive pulmonary disease (COPD) and has been associated with an increased risk of pneumonia. is one of the most common bacterial causes of infectious exacerbation in COPD. Currently, to our knowledge, no studies have investigated if ICS increases the risk of lower respiratory tract infection with in patients with COPD.
OBJECTIVE
To investigate if accumulated ICS use in patients with COPD, is associated with a dose-dependent risk of infection with .
METHODS
This observational cohort study included 18 870 persons with COPD who were registered in The Danish Register of COPD. Linkage to several nationwide registries was performed.Exposure to ICS was determined by identifying all prescriptions for ICS, redeemed within 365 days prior to study entry. Main outcome was a lower respiratory tract sample positive for . For the main analysis, a Cox multivariate regression model was used.We defined clinical infection as admission to hospital and/or a redeemed prescription for a relevant antibiotic, within 7 days prior to 14 days after the sample was obtained.
RESULTS
We found an increased, dose-dependent, risk of a lower respiratory tract sample with among patients who used ICS, compared with non-users. For low and moderate doses of ICS HR was 1.65 (95% CI 1.19 to 2.30, p=0.003) and 1.82 (95% CI 1.32 to 2.51, p=0.0002), respectively. In the group of patients with highest ICS exposure, the HR of was 2.80 (95% CI 2.06 to 3.82, p<0.0001). Results remained stable in sensitivity analyses. 87% of patients fulfilled the criteria for clinical infection, and results remained unchanged in this population.
CONCLUSION
Our study shows a dose-dependent increased risk of infection with associated to ICS exposure.
Topics: Humans; Moraxella catarrhalis; Respiratory Tract Infections; Patients; Pulmonary Disease, Chronic Obstructive; Adrenal Cortex Hormones
PubMed: 37597970
DOI: 10.1136/bmjresp-2023-001726 -
Journal of Clinical Pathology Jan 1963Two cases of human infection by Mima polymorpha are described. From these cases, and from the literature, it is concluded that this species is heterogeneous with respect...
Two cases of human infection by Mima polymorpha are described. From these cases, and from the literature, it is concluded that this species is heterogeneous with respect to its biochemical properties. From comparative studies it is concluded that the genus Mima is unrelated to the genus Moraxella or to Bacterium anitratum.
Topics: Acinetobacter; Bacillus; Humans; Moraxella
PubMed: 14015674
DOI: 10.1136/jcp.16.1.49