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Carbohydrate Polymers May 2024Published work has shown that glycoconjugate vaccines, based on truncated detoxified lipopolysaccharides from Moraxella catarrhalis attached through their reducing end...
Published work has shown that glycoconjugate vaccines, based on truncated detoxified lipopolysaccharides from Moraxella catarrhalis attached through their reducing end to a carrier protein, gave good protection for all three serotypes A, B, and C in mice immunisation experiments. The (from the non-reducing end) truncated LPS structures were obtained from bacterial glycosyl transferase knock-out mutants and contained the de-esterified Lipid A, two Kdo residues and five glucose moieties. This work describes the chemical synthesis of the same outer Moraxella LPS structures, spacer-equipped and further truncated from the reducing end, i.e., without the Lipid A part and containing four or five glucose moieties or four glucose moieties and one Kdo residue, and their subsequent conjugation to a carrier protein via a five‑carbon bifunctional spacer to form glycoconjugates. Immunisation experiments both in mice and rabbits of these gave a good antibody response, being 2-7 times that of pre-immune sera. However, the sera produced only recognized the immunizing glycan immunogens and failed to bind to native LPS or whole bacterial cells. Comparative molecular modelling of three alternative antigens shows that an additional (2 → 4)-linked Kdo residue, not present in the synthetic structures, has a significant impact on the shape and volume of the molecule, with implications for antigen binding and cross-reactivity.
Topics: Rabbits; Animals; Mice; Lipopolysaccharides; Moraxella catarrhalis; Lipid A; Antibodies, Bacterial; Glycoconjugates; Oligosaccharides; Glucose; Carrier Proteins
PubMed: 38431400
DOI: 10.1016/j.carbpol.2024.121928 -
The Journal of Allergy and Clinical... Jun 2024Five distinct respiratory phenotypes based on latent classes of longitudinal patterns of wheezing, allergic sensitization. and pulmonary function measured in urban...
BACKGROUND
Five distinct respiratory phenotypes based on latent classes of longitudinal patterns of wheezing, allergic sensitization. and pulmonary function measured in urban children from ages from 0 to 7 years have previously been described.
OBJECTIVE
Our aim was to determine whether distinct respiratory phenotypes are associated with early-life upper respiratory microbiota development and environmental microbial exposures.
METHODS
Microbiota profiling was performed using 16S ribosomal RNA-based sequencing of nasal samples collected at age 12 months (n = 120) or age 36 months (n = 142) and paired house dust samples collected at 3 months (12-month, n = 73; 36-month, n = 90) from all 4 centers in the Urban Environment and Childhood Asthma (URECA) cohort.
RESULTS
In these high-risk urban children, nasal microbiota increased in diversity between ages 12 and 36 months (ß = 2.04; P = .006). Age-related changes in microbiota evenness differed significantly by respiratory phenotypes (interaction P = .0007), increasing most in the transient wheeze group. At age 12 months, respiratory illness (R = 0.055; P = .0001) and dominant bacterial genus (R = 0.59; P = .0001) explained variance in nasal microbiota composition, and enrichment of Moraxella and Haemophilus members was associated with both transient and high-wheeze respiratory phenotypes. By age 36 months, nasal microbiota was significantly associated with respiratory phenotypes (R = 0.019; P = .0376), and Moraxella-dominated microbiota was associated specifically with atopy-associated phenotypes. Analysis of paired house dust and nasal samples indicated that 12 month olds with low wheeze and atopy incidence exhibited the largest number of shared bacterial taxa with their environment.
CONCLUSION
Nasal microbiota development over the course of early childhood and composition at age 3 years are associated with longitudinal respiratory phenotypes. These data provide evidence supporting an early-life window of airway microbiota development that is influenced by environmental microbial exposures in infancy and associates with wheeze- and atopy-associated respiratory phenotypes through age 7 years.
Topics: Humans; Infant; Microbiota; Child, Preschool; Male; Female; Phenotype; Urban Population; Respiratory Sounds; Longitudinal Studies; Asthma; Dust; Environmental Exposure; Nose; RNA, Ribosomal, 16S; Child
PubMed: 38423369
DOI: 10.1016/j.jaci.2023.12.032 -
American Journal of Veterinary Research May 2024To evaluate the prevalence of oral bacteria in the conjunctiva of brachycephalic and nonbrachycephalic dogs.
OBJECTIVE
To evaluate the prevalence of oral bacteria in the conjunctiva of brachycephalic and nonbrachycephalic dogs.
ANIMALS
12 brachycephalic (9.58 ± 3.55 years) and 12 nonbrachycephalic (8.33 ± 4.92 years) dogs without systemic disease, regardless of breed and sex, were included in the study, and half of the dogs in each group had periodontitis.
METHODS
This prospective study investigated clinical data including craniofacial ratio, ophthalmic examination results, and periodontal status of the included dogs. Bacterial samples were collected by swabbing the oral mucosa and conjunctival surfaces. The presence and quantity of bacteria were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, 16S rRNA sequencing analysis, and the 10-fold dilution method. Statistical analyses were performed to assess correlations and factors influencing the presence of oral bacteria in the conjunctiva.
RESULTS
The most common bacteria in the conjunctival flora in both groups were Micrococcus luteus, Corynebacterium spp, and Staphylococcus spp. The prevalence of oral bacteria on the conjunctival surface was 33%, with a significantly higher incidence in brachycephalic dogs (P = .027). Oral bacteria detected in the conjunctiva were predominantly Frederiksenia canicola, Neisseria spp, and Moraxella spp. Multiple regression analysis identified age, craniofacial ratio, and gingival index as factors influencing the presence of oral bacteria in the conjunctival flora.
CLINICAL RELEVANCE
Oral resident bacteria have often been isolated from severe infectious corneal ulcers. This study provided evidence that brachycephalic dogs may require dental prophylaxis to reduce their oral bacterial load and that the association of oral bacteria in ocular diseases should be considered.
Topics: Animals; Dogs; Conjunctiva; Female; Male; Dog Diseases; Prospective Studies; Craniosynostoses; RNA, Ribosomal, 16S; Mouth; Bacteria
PubMed: 38422613
DOI: 10.2460/ajvr.23.11.0260 -
Frontiers in Veterinary Science 2024It has been recognized that capripoxvirus infections have a strong cutaneous tropism with the manifestation of skin lesions in the form of nodules and scabs in the...
INTRODUCTION
It has been recognized that capripoxvirus infections have a strong cutaneous tropism with the manifestation of skin lesions in the form of nodules and scabs in the respective hosts, followed by necrosis and sloughing off. Considering that the skin microbiota is a complex community of commensal bacteria, fungi and viruses that are influenced by infections leading to pathological states, there is no evidence on how the skin microbiome is affected during capripoxvirus pathogenesis.
METHODS
In this study, shotgun metagenomic sequencing was used to investigate the microbiome in pox lesions from hosts infected with lumpy skin disease virus and sheep pox virus.
RESULTS
The analysis revealed a high degree of variability in bacterial community structures across affected skin samples, indicating the importance of specific commensal microorganisms colonizing individual hosts. The most common and abundant bacteria found in scab samples were , , and , irrespective of host. Bacterial reads belonging to the genera , , , and were identified.
DISCUSSION
This study is the first to investigate capripox virus-associated changes in the skin microbiome using whole-genome metagenomic profiling. The findings will provide a basis for further investigation into capripoxvirus pathogenesis. In addition, this study highlights the challenge of selecting an optimal bioinformatics approach for the analysis of metagenomic data in clinical and veterinary practice. For example, direct classification of reads using a kmer-based algorithm resulted in a significant number of systematic false positives, which may be attributed to the peculiarities of the algorithm and database selection. On the contrary, the process of assembly requires a large number of target reads from the symbiotic microbial community. In this work, the obtained sequencing data were processed by three different approaches, including direct classification of reads based on k-mers, mapping of reads to a marker gene database, and assembly and binning of metagenomic contigs. The advantages and disadvantages of these techniques and their practicality in veterinary settings are discussed in relation to the results obtained.
PubMed: 38420205
DOI: 10.3389/fvets.2024.1321202 -
International Journal of Systematic and... Feb 2024A novel species of the genus was isolated from an ocular swab from a cow with infectious bovine keratoconjunctivitis. 16S rRNA gene sequencing suggested this species...
A novel species of the genus was isolated from an ocular swab from a cow with infectious bovine keratoconjunctivitis. 16S rRNA gene sequencing suggested this species was (99.59 % nucleotide identity). Average nucleotide identity was calculated using a draft whole genome sequence of this strain compared with type strains of closely related species and results established that it represents a new species. The genome size was 2 006 474 nucleotides and the G+C content was 42.51 mol%. The species could not be identified by matrix assisted laser desorption/ionization-time of flight mass spectrometry using a commercial database, confirming the novelty of the strain. We propose the name sp. nov. for this new species. The type strain is Tifton1 and has been deposited into the American Type Culture Collection (TSD-373) and the National Collection of Type Cultures (NCTC), UK Health Security Agency (NCTC 14942).
Topics: Cattle; Animals; Moraxella; RNA, Ribosomal, 16S; Keratoconjunctivitis, Infectious; Phylogeny; Cattle Diseases; DNA, Bacterial; Bacterial Typing Techniques; Base Composition; Sequence Analysis, DNA; Fatty Acids; Keratoconjunctivitis; Moraxellaceae Infections; Nucleotides
PubMed: 38415687
DOI: 10.1099/ijsem.0.006281 -
Frontiers in Immunology 2024Bronchiolitis, a viral lower respiratory infection, is the leading cause of infant hospitalization, which is associated with an increased risk for developing asthma...
Bronchiolitis, a viral lower respiratory infection, is the leading cause of infant hospitalization, which is associated with an increased risk for developing asthma later in life. Bronchiolitis can be caused by several respiratory viruses, such as respiratory syncytial virus (RSV), rhinovirus (RV), and others. It can also be caused by a solo infection (e.g., RSV- or RV-only bronchiolitis) or co-infection with two or more viruses. Studies have shown viral etiology-related differences between RSV- and RV-only bronchiolitis in the immune response, human microRNA (miRNA) profiles, and dominance of certain airway microbiome constituents. Here, we identified bacterial small RNAs (sRNAs), the prokaryotic equivalent to eukaryotic miRNAs, that differ between infants of the 35 Multicenter Airway Research Collaboration (MARC-35) cohort with RSV- versus RV-only bronchiolitis. We first derived reference sRNA datasets from cultures of four bacteria known to be associated with bronchiolitis (i.e., , , , and ). Using these reference sRNA datasets, we found several sRNAs associated with RSV- and RV-only bronchiolitis in our human nasal RNA-Seq MARC-35 data. We also determined potential human transcript targets of the bacterial sRNAs and compared expression of the sRNAs between RSV- and RV-only cases. sRNAs are known to downregulate their mRNA target, we found that, compared to those associated with RV-only bronchiolitis, sRNAs associated with RSV-only bronchiolitis may relatively activate the IL-6 and IL-8 pathways and relatively inhibit the IL-17A pathway. These data support that bacteria may be contributing to inflammation differences seen in RSV- and RV-only bronchiolitis, and for the first time indicate that the potential mechanism in doing so may be through bacterial sRNAs.
Topics: Infant; Humans; Rhinovirus; RNA, Bacterial; Bronchiolitis; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Viruses; MicroRNAs; Enterovirus Infections; Immunity
PubMed: 38410509
DOI: 10.3389/fimmu.2024.1330991 -
Revista Argentina de Microbiologia 2024Infectious bovine keratoconjunctivitis (IBK) is an ocular disease that affects bovines and has significant economic and health effects worldwide. Gram negative bacteria...
Infectious bovine keratoconjunctivitis (IBK) is an ocular disease that affects bovines and has significant economic and health effects worldwide. Gram negative bacteria Moraxella bovis and Moraxella bovoculi are its main etiological agents. Antimicrobial therapy against IBK is often difficult in beef and dairy herds and, although vaccines are commercially available, their efficacy is variable and dependent on local strains. The aim of this study was to analyze for the first time the genomes of Uruguayan clinical isolates of M. bovis and M. bovoculi. The genomes were de novo assembled and annotated; the genetic basis of fimbrial synthesis was analyzed and virulence factors were identified. A 94% coverage in the reference genomes of both species, and more than 80% similarity to the reference genomes were observed. The mechanism of fimbrial phase variation in M. bovis was detected, and the tfpQ orientation of these genes confirmed, in an inversion region of approximately 2.18kb. No phase variation was determined in the fimbrial gene of M. bovoculi. When virulence factors were compared between strains, it was observed that fimbrial genes have 36.2% sequence similarity. In contrast, the TonB-dependent lactoferrin/transferrin receptor exhibited the highest percentage of amino acid similarity (97.7%) between strains, followed by cytotoxins MbxA/MbvA and the ferric uptake regulator. The role of these virulence factors in the pathogenesis of IBK and their potential as vaccine components should be explored.
Topics: Animals; Moraxella; Cattle; Moraxella bovis; Keratoconjunctivitis, Infectious; Cattle Diseases; Genome, Bacterial; Moraxellaceae Infections; Uruguay; Virulence Factors
PubMed: 38403533
DOI: 10.1016/j.ram.2023.12.003 -
Vaccines Feb 2024Chronic obstructive pulmonary disease (COPD) is a frequent, often progressive, chronic disease of the lungs. Patients with COPD often have impaired immunity; therefore,... (Review)
Review
Chronic obstructive pulmonary disease (COPD) is a frequent, often progressive, chronic disease of the lungs. Patients with COPD often have impaired immunity; therefore, they are prone to chest infections, such as pneumonia or bronchitis. Acute exacerbations of COPD are major events that accelerate disease progression, contributing to its symptoms' burden, morbidity, and mortality. Both pneumonia and acute exacerbations in COPD are caused by bacteria against which there are effective vaccinations. Although the number of randomised controlled studies on bacterial vaccinations in COPD is limited, national and international guidelines endorse specific vaccinations in patients with COPD. This review will summarise the different types of vaccinations that prevent pneumonia and COPD exacerbations. We also discuss the results of early phase studies. We will mainly focus on , as this bacterium was predominantly investigated in COPD. However, we also review studies investigating vaccinations against , , and .
PubMed: 38400196
DOI: 10.3390/vaccines12020213 -
Microorganisms Jan 2024, a commensal in the human nasopharynx, plays a significant role in the acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Its pathogenicity involves...
, a commensal in the human nasopharynx, plays a significant role in the acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Its pathogenicity involves adherence to respiratory epithelial cells, leading to infection through a macropinocytosis-like mechanism. Previous investigations highlighted the diverse abilities of isolates with different phenotypes to adhere to and invade respiratory epithelial cells. This study used a murine COPD model and in vitro experiments to explore the factors influencing the pathogenicity of distinct phenotypes of . Transcriptome sequencing suggested a potential association between actin cytoskeleton regulation and the infection of lung epithelial cells by with different phenotypes. Electron microscopy and Western blot analyses revealed a decrease in filamentous actin (F-actin) expression upon infection with various phenotypes. Inhibition of actin polymerization indicated the involvement of F-actin dynamics in internalization, distinguishing it from the adhesion process. Notably, hindering F-actin polymerization impaired the internalization of . These findings contribute vital theoretical insights for developing preventive strategies and individualized clinical treatments for AECOPD patients infected with . The study underscores the importance of understanding the nuanced interactions between phenotypes and host lung epithelial cells, offering valuable implications for the management of AECOPD infections.
PubMed: 38399695
DOI: 10.3390/microorganisms12020291 -
Antibiotics (Basel, Switzerland) Feb 2024The impact of bacterial pneumonia on patients with COVID-19 infection remains unclear. This prospective observational monocentric cohort study aims to determine the...
The impact of bacterial pneumonia on patients with COVID-19 infection remains unclear. This prospective observational monocentric cohort study aims to determine the incidence of bacterial community- and hospital-acquired pneumonia (CAP and HAP) and its effect on mortality in critically ill COVID-19 patients admitted to the intensive care unit (ICU) at University Hospital Olomouc between 1 November 2020 and 31 December 2022. The secondary objectives of this study include identifying the bacterial etiology of CAP and HAP and exploring the capabilities of diagnostic tools, with a focus on inflammatory biomarkers. Data were collected from the electronic information hospital system, encompassing biomarkers, microbiological findings, and daily visit records, and subsequently evaluated by ICU physicians and clinical microbiologists. Out of 171 patients suffering from critical COVID-19, 46 (27%) had CAP, while 78 (46%) developed HAP. Critically ill COVID-19 patients who experienced bacterial CAP and HAP exhibited higher mortality compared to COVID-19 patients without any bacterial infection, with rates of 38% and 56% versus 11%, respectively. In CAP, the most frequent causative agents were chlamydophila and mycoplasma; Enterobacterales, which were multidrug-resistant in 71% of cases; Gram-negative non-fermenting rods; and . Notably, no strains of were detected, and only a single strain each of and was isolated. The most frequent etiologic agents causing HAP were Enterobacterales and Gram-negative non-fermenting rods. Based on the presented results, commonly used biochemical markers demonstrated poor predictive and diagnostic accuracy. To confirm the diagnosis of bacterial CAP in our patient cohort, it was necessary to assess the initial values of inflammatory markers (particularly procalcitonin), consider clinical signs indicative of bacterial infection, and/or rely on positive microbiological findings. For HAP diagnostics, it was appropriate to conduct regular detailed clinical examinations (with a focus on evaluating respiratory functions) and closely monitor the dynamics of inflammatory markers (preferably Interleukin-6).
PubMed: 38391578
DOI: 10.3390/antibiotics13020192