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Frontiers in Cellular and Infection... 2022Rhinovirus causes many types of respiratory illnesses, ranging from minor colds to exacerbations of asthma. is an opportunistic pathogen that is increased in abundance...
Rhinovirus causes many types of respiratory illnesses, ranging from minor colds to exacerbations of asthma. is an opportunistic pathogen that is increased in abundance during rhinovirus illnesses and asthma exacerbations and is associated with increased severity of illness through mechanisms that are ill-defined. We used a co-infection model of human airway epithelium differentiated at the air-liquid interface to test the hypothesis that rhinovirus infection promotes adhesion and survival on the respiratory epithelium. Initial experiments showed that infection with alone did not damage the epithelium or induce cytokine production, but increased trans-epithelial electrical resistance, indicative of increased barrier function. In a co-infection model, infection with the more virulent rhinovirus-A and rhinovirus-C, but not the less virulent rhinovirus-B types, increased cell-associated . Immunofluorescent staining demonstrated that adhered to rhinovirus-infected ciliated epithelial cells and infected cells being extruded from the epithelium. Rhinovirus induced pronounced changes in gene expression and secretion of inflammatory cytokines. In contrast, caused minimal effects and did not enhance RV-induced responses. Our results indicate that rhinovirus-A or C infection increases survival and cell association while infection alone does not cause cytopathology or epithelial inflammation. Our findings suggest that rhinovirus and co-infection could promote epithelial damage and more severe illness by amplifying leukocyte inflammatory responses at the epithelial surface.
Topics: Humans; Moraxella catarrhalis; Rhinovirus; Coinfection; Respiratory Mucosa; Asthma; Epithelial Cells; Enterovirus Infections
PubMed: 36733852
DOI: 10.3389/fcimb.2022.1060748 -
Journal of Clinical Pathology Nov 1972Eight strains of Moraxella phenylpyruvica have been isolated from clinical material in the United Kingdom, the first to be reported from this country. They were...
Eight strains of Moraxella phenylpyruvica have been isolated from clinical material in the United Kingdom, the first to be reported from this country. They were characterized, together with three strains of M. phenylpyruvica of the National Collection of Type Cultures (NCTC), and compared with NCTC strains of eight other Moraxella species. The strains of M. phenylpyruvica formed a homogeneous group which is readily distinguishable from other Moraxella species. Deamination of phenylalanine is not restricted to M. phenylpyruvica which, however, is urease positive and is stimulated by bile, in contrast to other Moraxella spp.
Topics: Adult; Aged; Bartholin's Glands; Bile; Child; Child, Preschool; Culture Media; Cysts; DNA, Bacterial; Female; Gastroenteritis; Humans; Infant; Leg Ulcer; Male; Microbial Sensitivity Tests; Moraxella; Phenylalanine; Pre-Eclampsia; Pregnancy; Pressure Ulcer; Pulmonary Fibrosis; Urease; Vaginal Diseases; Vulvovaginitis
PubMed: 4648540
DOI: 10.1136/jcp.25.11.959 -
Journal of Veterinary Diagnostic... Sep 2018Infectious bovine keratoconjunctivitis (IBK) is an economically significant disease caused by Moraxella bovis. Moraxella bovoculi, although not reported to cause IBK,...
Infectious bovine keratoconjunctivitis (IBK) is an economically significant disease caused by Moraxella bovis. Moraxella bovoculi, although not reported to cause IBK, has been isolated from the eyes of cattle diagnosed with IBK. Identification of M. bovis and M. bovoculi can be performed using biochemical or DNA-based approaches, both of which may be time consuming and inconsistent between laboratories. We conducted a comparative evaluation of M. bovoculi and M. bovis identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with a database provided by Bruker Daltonics (termed the BDAL database), the BDAL database supplemented with spectra generated in our study (termed the UNLVDC database), and with PCR-restriction-fragment length polymorphism (PCR-RFLP) typing. M. bovoculi ( n = 250) and M. bovis ( n = 18) isolates from cattle with or without IBK were used. MALDI-TOF MS using the UNLVDC database correctly identified 250 of 250 (100%) of M. bovoculi and 17 of 18 (94%) of M. bovis isolates. With the BDAL database, MALDI-TOF MS correctly identified 249 of 250 (99%) of M. bovoculi and 7 of 18 (39%) of M. bovis isolates. In comparison, the PCR-RFLP test correctly identified 210 of 250 (84%) of M. bovoculi and 12 of 18 (66%) of M. bovis isolates. Thus, MALDI-TOF MS with the UNLVDC database was the most effective identification methodology for M. bovis and M. bovoculi isolates from cattle.
Topics: Animals; Cattle; Cattle Diseases; Databases, Factual; Keratoconjunctivitis, Infectious; Mass Spectrometry; Moraxella; Moraxella bovis; Moraxellaceae Infections; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Sensitivity and Specificity; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 30027824
DOI: 10.1177/1040638718789725 -
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 -
Science (New York, N.Y.) Oct 2018Cas12a (Cpf1) is a CRISPR-associated nuclease with broad utility for synthetic genome engineering, agricultural genomics, and biomedical applications. Although bacteria...
Cas12a (Cpf1) is a CRISPR-associated nuclease with broad utility for synthetic genome engineering, agricultural genomics, and biomedical applications. Although bacteria harboring CRISPR-Cas9 or CRISPR-Cas3 adaptive immune systems sometimes acquire mobile genetic elements encoding anti-CRISPR proteins that inhibit Cas9, Cas3, or the DNA-binding Cascade complex, no such inhibitors have been found for CRISPR-Cas12a. Here we use a comprehensive bioinformatic and experimental screening approach to identify three different inhibitors that block or diminish CRISPR-Cas12a-mediated genome editing in human cells. We also find a widespread connection between CRISPR self-targeting and inhibitor prevalence in prokaryotic genomes, suggesting a straightforward path to the discovery of many more anti-CRISPRs from the microbial world.
Topics: Bacterial Proteins; CRISPR-Cas Systems; Cell Line; Computational Biology; DNA Cleavage; Endonucleases; Gene Editing; Genome, Bacterial; Humans; Moraxella
PubMed: 30190307
DOI: 10.1126/science.aau5138 -
Infection and Immunity Sep 2015Several bacterial species recruit the complement regulators C4b-binding protein, factor H, and vitronectin, resulting in resistance against the bactericidal activity of...
Several bacterial species recruit the complement regulators C4b-binding protein, factor H, and vitronectin, resulting in resistance against the bactericidal activity of human serum. It was recently demonstrated that bacteria also bind plasminogen, which is converted to plasmin that degrades C3b and C5. In this study, we found that a series of clinical isolates (n = 58) of the respiratory pathogen Moraxella catarrhalis, which is commonly isolated from preschool children and adults with chronic obstructive pulmonary disease (COPD), significantly binds human plasminogen. Ubiquitous surface protein A2 (UspA2) and hybrid UspA2 (UspA2H) were identified as the plasminogen-binding factors in the outer membrane proteome of Moraxella. Furthermore, expression of a series of truncated recombinant UspA2 and UspA2H proteins followed by a detailed analysis of protein-protein interactions suggested that the N-terminal head domains bound to the kringle domains of plasminogen. The binding affinity constant (KD) values of full-length UspA2(30-539) (amino acids 30 to 539 of UspA2) and full-length UspA2H(50-720) for immobilized plasminogen were 4.8 × 10(-8) M and 3.13 × 10(-8) M, respectively, as measured by biolayer interferometry. Plasminogen bound to intact M. catarrhalis or to recombinant UspA2/UspA2H was readily accessible for a urokinase plasminogen activator that converted the zymogen into active plasmin, as verified by the specific substrate S-2251 and a degradation assay with fibrinogen. Importantly, plasmin bound at the bacterial surface also degraded C3b and C5, which consequently may contribute to reduced bacterial killing. Our findings suggest that binding of plasminogen to M. catarrhalis may lead to increased virulence and, hence, more efficient colonization of the host.
Topics: Bacterial Outer Membrane Proteins; Enzyme-Linked Immunosorbent Assay; Humans; Immune Evasion; Immunity, Innate; Moraxella catarrhalis; Moraxellaceae Infections; Plasminogen
PubMed: 26099590
DOI: 10.1128/IAI.00310-15 -
BMJ Case Reports Apr 2021
Topics: Hockey; Humans; Moraxella catarrhalis; Moraxellaceae Infections
PubMed: 33931430
DOI: 10.1136/bcr-2021-243677 -
Journal of Infection in Developing... Nov 2013Infectious bovine keratoconjunctivitis (IBK) is the most common ocular disease that affects cattle throughout the world and it has a very significant economic impact....
BACKGROUND
Infectious bovine keratoconjunctivitis (IBK) is the most common ocular disease that affects cattle throughout the world and it has a very significant economic impact. IBK is caused by members of the genus Moraxella and therapeutic and preventive measures have shown limited success. Vaccines, most of them chemically inactivated bacterins, generally induce a limited protection.
METHODOLOGY
In this study, the genetic diversity of Uruguayan clinical Moraxella bovis and Moraxella bovoculi isolates was assessed by RAPD-PCR, ERIC-PCR and BOX-PCR fingerprinting. Also, antibiotic resistance of the Moraxella spp. isolates was assessed utilizing the disk diffusion method.
RESULTS
When interspecific molecular diversity was assessed, different bands patterns were observed even within a single outbreak of IBK, showing the coexistence of different genotypes of Moraxella spp. The high genetic diversity within M. bovis and M. bovoculi isolates did not permit to correlate isolates DNA fingerprints with geographical origins, dates or even with both different Moraxella species. Antibiotics resistance patterns showed significant differences between M. bovis and M. bovoculi.
CONCLUSIONS
This is the first study of diversity that includes M. bovis and M. bovoculi associated to IBK cases. Genetic diversity did not allow to correlate DNA fingerprints of the isolates with geographical origins, isolation dates or even both different Moraxella species. Antibiotics resistance patterns showed differences between M. bovis and M. bovoculi. This remarkable variation within isolates could explain the partial protection induced by commercial vaccines. All these findings could be important for the design of prevention or treatment strategies against IBK.
Topics: Animals; Cattle; Cattle Diseases; DNA Fingerprinting; Genetic Variation; Keratoconjunctivitis, Infectious; Microbial Sensitivity Tests; Molecular Typing; Moraxella; Uruguay
PubMed: 24240039
DOI: 10.3855/jidc.3458 -
Microbiome Jun 2018Perturbations to the composition and function of bronchial bacterial communities appear to contribute to the pathophysiology of asthma. Unraveling the nature and...
BACKGROUND
Perturbations to the composition and function of bronchial bacterial communities appear to contribute to the pathophysiology of asthma. Unraveling the nature and mechanisms of these complex associations will require large longitudinal studies, for which bronchoscopy is poorly suited. Studies of samples obtained by sputum induction and nasopharyngeal brushing or lavage have also reported asthma-associated microbiota characteristics. It remains unknown, however, whether the microbiota detected in these less-invasive sample types reflect the composition of bronchial microbiota in asthma.
RESULTS
Bacterial microbiota in paired protected bronchial brushings (BB; n = 45), induced sputum (IS; n = 45), oral wash (OW; n = 45), and nasal brushings (NB; n = 27) from adults with mild atopic asthma (AA), atopy without asthma (ANA), and healthy controls (HC) were profiled using 16S rRNA gene sequencing. Though microbiota composition varied with sample type (p < 0.001), compositional similarity was greatest for BB-IS, particularly in AAs and ANAs. The abundance of genera detected in BB correlated with those detected in IS and OW (r median [IQR] 0.869 [0.748-0.942] and 0.822 [0.687-0.909] respectively), but not with those in NB (r = 0.004 [- 0.003-0.011]). The number of taxa shared between IS-BB and NB-BB was greater in AAs than in HCs (p < 0.05) and included taxa previously associated with asthma. Of the genera abundant in NB, only Moraxella correlated positively with abundance in BB; specific members of this genus were shared between the two compartments only in AAs. Relative abundance of Moraxella in NB of AAs correlated negatively with that of Corynebacterium but positively with markers of eosinophilic inflammation in the blood and BAL fluid. The genus, Corynebacterium, trended to dominate all NB samples of HCs but only half of AAs (p = 0.07), in whom abundance of this genus was negatively associated with markers of eosinophilic inflammation.
CONCLUSIONS
Induced sputum is superior to nasal brush or oral wash for assessing bronchial microbiota composition in asthmatic adults. Although compositionally similar to the bronchial microbiota, the microbiota in induced sputum are distinct, reflecting enrichment of oral bacteria. Specific bacterial genera are shared between the nasal and the bronchial mucosa which are associated with markers of systemic and bronchial inflammation.
Topics: Adult; Asthma; Bronchi; Corynebacterium; Eosinophils; Female; Humans; Inflammation; Male; Microbiota; Middle Aged; Moraxella; Mouth Mucosa; Nose; RNA, Ribosomal, 16S; Sputum
PubMed: 29885665
DOI: 10.1186/s40168-018-0487-3 -
BMC Microbiology Sep 2009Bacteriocins are antimicrobial proteins and peptides ribosomally synthesized by some bacteria which can effect both intraspecies and interspecies killing.
BACKGROUND
Bacteriocins are antimicrobial proteins and peptides ribosomally synthesized by some bacteria which can effect both intraspecies and interspecies killing.
RESULTS
Moraxella catarrhalis strain E22 containing plasmid pLQ510 was shown to inhibit the growth of M. catarrhalis strain O35E. Two genes (mcbA and mcbB) in pLQ510 encoded proteins predicted to be involved in the secretion of a bacteriocin. Immediately downstream from these two genes, a very short ORF (mcbC) encoded a protein which had some homology to double-glycine bacteriocins produced by other bacteria. A second very short ORF (mcbI) immediately downstream from mcbC encoded a protein which had no significant similarity to other proteins in the databases. Cloning and expression of the mcbI gene in M. catarrhalis O35E indicated that this gene encoded the cognate immunity factor. Reverse transcriptase-PCR was used to show that the mcbA, mcbB, mcbC, and mcbI ORFs were transcriptionally linked. This four-gene cluster was subsequently shown to be present in the chromosome of several M. catarrhalis strains including O12E. Inactivation of the mcbA, mcbB, or mcbC ORFs in M. catarrhalis O12E eliminated the ability of this strain to inhibit the growth of M. catarrhalis O35E. In co-culture experiments involving a M. catarrhalis strain containing the mcbABCI locus and one which lacked this locus, the former strain became the predominant member of the culture after overnight growth in broth.
CONCLUSION
This is the first description of a bacteriocin and its cognate immunity factor produced by M. catarrhalis. The killing activity of the McbC protein raises the possibility that it might serve to lyse other M. catarrhalis strains that lack the mcbABCI locus, thereby making their DNA available for lateral gene transfer.
Topics: Amino Acid Sequence; Antibiosis; Bacteriocins; Cloning, Molecular; DNA, Bacterial; Gene Expression Regulation, Bacterial; Genes, Bacterial; Molecular Sequence Data; Moraxella catarrhalis; Multigene Family; Open Reading Frames; Plasmids; Sequence Deletion
PubMed: 19781080
DOI: 10.1186/1471-2180-9-207