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1.
Vaccine ; 39(39): 5641-5649, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34446318

RESUMO

Moraxella catarrhalis (Mcat) is a key pathogen associated with exacerbations of chronic obstructive pulmonary disease (COPD) in adults and playing a significant role in otitis media in children. A vaccine would help to reduce the morbidity and mortality associated with these diseases. UspA2 is an Mcat surface antigen considered earlier as vaccine candidate before the interest in this molecule vanished due to sequence variability. However, the observation that some conserved domains are the target of bactericidal antibodies prompted us to reconsider UspA2 as a potential vaccine antigen. We first determined its prevalence among the COPD patients from the AERIS study, as the prevalence of UspA2 in a COPD-restricted population had yet to be documented. The gene was found in all Mcat isolates either as UspA2 or UspA2H variant. The percentage of UspA2H variant was higher than in any report so far, reaching 51%. A potential link between the role of UspA2H in biofilm formation and this high prevalence is discussed. To study further UspA2 as a vaccine antigen, recombinant UspA2 molecules were designed and used in animal models and bactericidal assays. We showed that UspA2 is immunogenic and that UspA2 immunization clears Mcat pulmonary challenge in a mouse model. In a serum bactericidal assay, anti-UspA2 antibodies generated in mice, guinea pigs or rabbits were able to kill Mcat strains of various origins, including a subset of isolates from the AERIS study, cross-reacting with UspA2H and even UspA1, a closely related Mcat surface protein. In conclusion, UspA2 is a cross-reactive Mcat antigen presenting the characteristics of a vaccine candidate.


Assuntos
Moraxella catarrhalis , Otite Média , Animais , Antígenos de Superfície , Proteínas da Membrana Bacteriana Externa , Reações Cruzadas , Cobaias , Humanos , Camundongos , Coelhos
2.
Int J Pediatr Otorhinolaryngol ; 149: 110848, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34304116

RESUMO

BACKGROUND: Despite a far from perfect correlation with middle ear growth, nasopharyngeal cultures are sometimes used in children with acute otitis media (AOM) in order to have some idea of the causative pathogen. How these cultures are used in clinical practice and to what extent they influence clinical management has not previously been studied. The objective with this study was to investigate in what circumstances nasopharyngeal cultures are performed in children with AOM, what the bacteriological results are and to what extent cultures influence clinical management. METHODS: All nasopharyngeal cultures taken in clinical practice from children with AOM in the county of Skåne, Sweden, during 2017-2018 were retrieved together with details from the medical charts two months prior to and one month after the culture. Information about the reason for culturing, the bacteriological result, and whether this result changed the management of the child, was retrieved from the charts. RESULTS: During the 2 years, 978 nasopharyngeal cultures were taken in children with AOM. The most common reasons for obtaining a culture was a recurrence of AOM (40%) or treatment failure (22%). Many of the children had ongoing or recent antibiotic treatment. M. catarrhalis was the most commonly identified pathogen (53%), followed by H. influenzae (30%) and S. pneumoniae (14%). Resistance rates were low, and the most commonly identified resistant pathogen was betalactamase-negative ampicillin-resistant H. influenzae. One in five cultures led to a change in management, such as a change of antibiotics or an additional check-up. This was most commonly seen in association with H. influenzae, reflecting clinical practice in Sweden, where AOM is primarily treated with penicillin V. CONCLUSION: Despite not having a perfect correlation with middle ear growth, nasopharyngeal cultures can provide clues about suitable alternative antibiotics in cases of treatment failure, and they can help monitoring nasopharyngeal carriage and resistance rates.


Assuntos
Nasofaringe , Otite Média , Doença Aguda , Criança , Humanos , Moraxella catarrhalis , Estudos Retrospectivos
3.
PLoS One ; 16(6): e0253402, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34138947

RESUMO

Classification of clinical symptoms and diagnostic microbiology are essential to effectively employ antimicrobial therapy for lower respiratory tract infections (LRTIs) in a timely manner. Empirical antibiotic treatment without microbial identification hinders the selective use of narrow-spectrum antibiotics and effective patient treatment. Thus, the development of rapid and accurate diagnostic procedures that can be readily adopted by the clinic is necessary to minimize non-essential or excessive use of antibiotics and accelerate patient recovery from LRTI-induced damage. We developed and validated a multiplex real-time polymerase chain reaction (mRT-PCR) assay with good analytical performance and high specificity to simultaneously detect four bacterial pathogens causing pneumonia: Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Moraxella catarrhalis. The analytical performance of mRT-PCR against target pathogens was evaluated by the limit of detection (LOD), specificity, and repeatability. Two hundred and ten clinical specimens from pneumonia patients were processed using an automatic nucleic acid extraction system for the "respiratory bacteria four" (RB4) mRT-PCR assay, and the results were directly compared to references from bacterial culture and/or Sanger sequencing. The RB4 mRT-PCR assay detected all target pathogens from sputum specimens with a coefficient of variation ranging from 0.29 to 1.71 and conservative LOD of DNA corresponding to 5 × 102 copies/reaction. The concordance of the assay with reference-positive specimens was 100%, and additional bacterial infections were detected from reference-negative specimens. Overall, the RB4 mRT-PCR assay showed a more rapid turnaround time and higher performance that those of reference assays. The RB4 mRT-PCR assay is a high-throughput and reliable tool that assists decision-making assessment and outperforms other standard methods. This tool supports patient management by considerably reducing the inappropriate use of antibiotics.


Assuntos
Klebsiella pneumoniae/isolamento & purificação , Moraxella catarrhalis/isolamento & purificação , Pneumonia/diagnóstico , Pseudomonas aeruginosa/isolamento & purificação , Staphylococcus aureus/isolamento & purificação , Humanos , Reação em Cadeia da Polimerase Multiplex/métodos , Pneumonia/microbiologia , Sensibilidade e Especificidade
4.
J Biol Regul Homeost Agents ; 35(3): 847-863, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34155874

RESUMO

Respiratory infections (RI) significantly burden patients, their families, and society. Respiratory infection recurrence (RRI) usually depends on a defect of the immune response, which can be more or less transient and/or selective. In particular, children, older people, heavy smokers, and patients with chronic diseases, characterized by an inadequate immune response, may be at risk of developing RRI. In this context, OM- 85 could represent a valuable option in the management of RRI. OM-85 is a bacterial lysate containing the extracts of some common pathogens, including Branhamella catarrhalis, Klebsiella pneumoniae, Klebsiella ozaenae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, and Staphylococcus aureus. Methodologically rigorous studies have documented the mechanism of action, efficacy, and safety of OM-85. OM-85 enhances the natural and acquired immune response through multifaceted mechanisms. Substantial evidence has shown that OM-85 can prevent respiratory infections, reduce the number of COPD exacerbations, and shorten the disease duration at home or in hospital. OM-85 can enhance the effectiveness of the 'flu vaccination without affecting the vaccine tolerability. The preventive use of OM-85 can reduce the use of antibiotics, contributing to contrast antibiotic resistance and saving the high cost of chronic respiratory diseases. Further studies should define the ideal candidate to OM-85 treatment.


Assuntos
Klebsiella , Infecções Respiratórias , Idoso , Criança , Humanos , Moraxella catarrhalis , Infecções Respiratórias/prevenção & controle , Streptococcus pneumoniae
5.
Pediatr Pulmonol ; 56(8): 2634-2641, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33969642

RESUMO

INTRODUCTION: Pediatric flexible laryngotracheal bronchoscopy (FB) is an integral part of diagnostics and treatment at tertiary pediatric respiratory centers. AIM: FBs performed between 2013 and 2018 at our Pediatric Allergy and Respiratory Medicine Unit of the Department of Women's and Children's Health at Padua University were examined in terms of the indications, findings, and adverse events. MATERIALS AND METHODS: The electronic medical records of pediatric patients who underwent FB at least once between 1 January 2013 and 31 December 2018 were considered. Patients' clinical data, indications for FB, anatomical findings, information derived from bronchoalveolar lavage (BAL) and bronchial brushing, and possible adverse events were analyzed. RESULTS: There were 447 pediatric FBs performed in 428 patients (aged from 1 month to 18 years) for diagnostic purposes (92.4%), to clear secretions (3.6%), or to monitor a known condition (4.0%). The main indications were recurrent lower respiratory tract infections (LRTI, 32.2%) and chronic wet cough (9.4%). Lower airway malacia was the most common abnormal finding in these two groups (36.1% and 28.6%, respectively). BAL bacterial culture was positive in 55 children (39.6%) with recurrent LRTI and in 25 (59.5%) with chronic wet cough, being Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis the microorganisms most commonly isolated. FB proved a safe procedure and was well tolerated. CONCLUSIONS: Pediatric FB is an essential tool at our tertiary pediatric respiratory center. It helps establish the anatomical conditions underlying several chronic respiratory conditions and any correlated microbiological findings, with a significant impact on further patient management.


Assuntos
Broncoscopia , Saúde da Criança , Lavagem Broncoalveolar , Criança , Feminino , Humanos , Lactente , Moraxella catarrhalis , Estudos Retrospectivos , Saúde da Mulher
7.
Rev Esp Quimioter ; 34(2): 81-92, 2021 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-33749214

RESUMO

From a microbiological point of view, both empirical and targeted antimicrobial treatment in respiratory infection is based on the sensitivity profile of isolated microorganisms and the possible resistance mechanisms that they may present. The latter may vary in different geographic areas according to prescription profiles and vaccination programs. Beta-lactam antibiotics, fluoroquinolones, and macrolides are the most commonly used antimicrobials during the exacerbations of chronic obstructive pulmonary disease and community-acquired pneumonia. In their prescription, different aspects such as intrinsic activity, bactericidal effect or their ability to prevent the development of resistance must be taken into account. The latter is related to the PK/PD parameters, the mutant prevention concentration and the so-called selection window. More recently, the potential ecological impact has grown in importance, not only on the intestinal microbiota, but also on the respiratory one. Maintaining the state of eubiosis requires the use of antimicrobials with a low profile of action on anaerobic bacteria. With their use, the resilience of the bacterial populations belonging to the microbiota, the state of resistance of colonization and the collateral damage related to the emergence of resistance to the antimicrobials in pathogens causing the infections and in the bacterial populations integrating the microbiota.


Assuntos
Antibacterianos/farmacologia , COVID-19/epidemiologia , Farmacorresistência Bacteriana , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Administração Oral , Antibacterianos/administração & dosagem , Chlamydophila pneumoniae/efeitos dos fármacos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Progressão da Doença , Microbioma Gastrointestinal/efeitos dos fármacos , Haemophilus influenzae/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Moraxella catarrhalis/efeitos dos fármacos , Mycoplasma pneumoniae/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/microbiologia , Infecções Respiratórias/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos
8.
Respir Res ; 22(1): 67, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627095

RESUMO

BACKGROUND: Infection with Haemophilus influenzae (Hi) or Moraxella catarrhalis (Mcat) is a risk factor for exacerbation in chronic obstructive pulmonary disease (COPD). The ability to predict Hi- or Mcat-associated exacerbations may be useful for interventions developed to reduce exacerbation frequency. METHODS: In a COPD observational study, sputum samples were collected at monthly stable-state visits and at exacerbation during two years of follow-up. Bacterial species (Hi, Mcat) were identified by culture and quantitative PCR assay. Post-hoc analyses were conducted to assess: (1) first Hi- or Mcat-positive exacerbations given presence or absence of Hi or Mcat at the screening visit (stable-state timepoint); (2) first Hi- or Mcat-positive exacerbations given presence or absence of Hi or Mcat at stable timepoints within previous 90 days; (3) second Hi- or Mcat-positive exacerbations given presence or absence of Hi or Mcat at stable timepoints within previous 90 days. Percentages and risk ratios (RRs) with 95% confidence intervals were calculated. RESULTS: PCR results for analyses 1, 2 and 3 (samples from 84, 88 and 83 subjects, respectively) showed that the risk of an Hi- or Mcat-positive exacerbation is significantly higher if sputum sample was Hi- or Mcat-positive than if Hi- or Mcat-negative at previous stable timepoints (apart from Mcat in analysis 3); RRs ranged from 2.1 to 3.2 for Hi and 1.9 to 2.6 for Mcat.For all analyses, the percentage of Hi- or Mcat-positive exacerbations given previous Hi- or Mcat-positive stable timepoints was higher than the percentage of Hi- or Mcat-positive exacerbations if Hi- or Mcat-negative at previous stable timepoints. Percentage of Hi- or Mcat-positive exacerbations given previous Hi- or Mcat-negative stable timepoints was 26.3%-37.0% for Hi and 17.6%-19.7% for Mcat. CONCLUSIONS: Presence of Hi or Mcat at a stable timepoint was associated with a higher risk of a subsequent Hi- or Mcat-associated exacerbation compared with earlier absence. However, a large percentage of Hi- or Mcat-associated exacerbations was not associated with Hi/Mcat detection at an earlier timepoint. This suggests that administration of an intervention to reduce these exacerbations should be independent of bacterial presence at baseline. Trial Registration https://clinicaltrials.gov/ ; NCT01360398, registered May 25, 2011.


Assuntos
DNA Bacteriano/análise , Haemophilus influenzae/genética , Moraxella catarrhalis/genética , Doença Pulmonar Obstrutiva Crônica/microbiologia , Escarro/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Haemophilus influenzae/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Moraxella catarrhalis/isolamento & purificação , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Recidiva , Fatores de Risco , Fatores de Tempo
9.
J Enzyme Inhib Med Chem ; 36(1): 384-393, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33406941

RESUMO

Joining the global fight against Tuberculosis, the world's most deadly infectious disease, herein we present the design and synthesis of novel isatin-nicotinohydrazide hybrids (5a-m and 9a-c) as promising anti-tubercular and antibacterial agents. The anti-tubercular activity of the target hybrids was evaluated against drug-susceptible M. tuberculosis strain (ATCC 27294) where hybrids 5d, 5g and 5h were found to be as potent as INH with MIC = 0.24 µg/mL, also the activity was evaluated against Isoniazid/Streptomycin resistant M. tuberculosis (ATCC 35823) where compounds 5g and 5h showed excellent activity (MIC = 3.9 µg/mL). Moreover, the target hybrids were examined against six bronchitis causing-bacteria. Most derivatives exhibited excellent antibacterial activity. K. pneumonia emerged as the most sensitive strain with MIC range: 0.49-7.81 µg/mL. Furthermore, a molecular docking study has proposed DprE1 as a probable enzymatic target for herein reported isatin-nicotinohydrazide hybrids, and explored the binding interactions within the vicinity of DprE1 active site.


Assuntos
Oxirredutases do Álcool/antagonistas & inibidores , Antibacterianos/síntese química , Proteínas de Bactérias/antagonistas & inibidores , Farmacorresistência Bacteriana/efeitos dos fármacos , Hidrazinas/química , Isatina/química , Mycobacterium tuberculosis/enzimologia , Oxirredutases do Álcool/química , Oxirredutases do Álcool/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Bordetella pertussis/química , Bordetella pertussis/enzimologia , Bordetella pertussis/isolamento & purificação , Bronquite/tratamento farmacológico , Bronquite/microbiologia , Desenho de Fármacos , Farmacorresistência Bacteriana/genética , Haemophilus influenzae/química , Haemophilus influenzae/enzimologia , Haemophilus influenzae/isolamento & purificação , Isoniazida/farmacologia , Klebsiella pneumoniae/química , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Moraxella catarrhalis/química , Moraxella catarrhalis/enzimologia , Moraxella catarrhalis/isolamento & purificação , Mycobacterium tuberculosis/química , Mycobacterium tuberculosis/isolamento & purificação , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Streptococcus pneumoniae/química , Streptococcus pneumoniae/enzimologia , Streptococcus pneumoniae/isolamento & purificação , Estreptomicina/farmacologia , Relação Estrutura-Atividade , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia
10.
Clin Microbiol Infect ; 27(4): 630.e1-630.e6, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32360778

RESUMO

OBJECTIVES: To study effects of the introduction of pneumococcal conjugate vaccines (PCV) on the interspecies dynamics of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in preschool children with respiratory tract infection. METHODS: Nasopharyngeal samples from children aged ≤6 years with upper respiratory tract infection (n = 14 473) in South Sweden were analysed during 14 consecutive years, 5 years before and 9 years after PCV introduction. The yearly prevalence was calculated, and multivariate count regressions between prevalence and estimated yearly proportions of vaccinated children were performed. Associations between pneumococcal serotypes and the other pathogens were assessed. RESULTS: When comparing the prevaccine period with the years after introduction, the prevalence of S. pneumoniae decreased by 65.2% (16.4 to 5.7 per 1000 individuals; p < 0.001), whereas M. catarrhalis and H. influenzae decreased by 52.1% (21.5 to 10.3 per 1000 individuals; p < 0.001) and 46.6% (13.6 to 7.3 per 1000 individuals; p < 0.001), respectively. In multivariate negative binomial regressions adjusted for yearly numbers of samples taken, S. pneumoniae and M. catarrhalis were significantly negatively associated with increasing vaccine coverage proportions (adjusted prevalence ratio (aPR) = 0.17; p < 0.001 and aPR = 0.48; p < 0.001, respectively), whereas H. influenzae (aPR = 0.75; p = 0.17) was not. In addition, the proportion of cultures positive for S. pneumoniae as well as M. catarrhalis was significantly lower in the postvaccine period compared to the prevaccine period, while this was not the case for H. influenzae. A significant positive association between certain PCV serotypes and simultaneous growth with M. catarrhalis was observed. CONCLUSIONS: After introduction of PCV, the prevalence of M. catarrhalis in addition to S. pneumoniae in children with respiratory tract infection decreased; this was also the case after adjusting for reduced numbers of samples taken. This may partly be attributed to a positive association between PCV serotypes and M. catarrhalis.


Assuntos
Moraxella catarrhalis/isolamento & purificação , Infecções por Moraxellaceae/prevenção & controle , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Infecções Respiratórias/microbiologia , Streptococcus pneumoniae/isolamento & purificação , Pré-Escolar , Estudos de Coortes , Haemophilus influenzae/isolamento & purificação , Humanos , Lactente , Nasofaringe/microbiologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Estudos Retrospectivos , Suécia/epidemiologia
11.
J Pathol ; 253(1): 1-10, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33044742

RESUMO

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) was suggested as an entity separate from other types of Hodgkin lymphoma 40 years ago and recognized in the WHO classification in 2001. Based on its relatively benign course with late distant relapses, relation with lymph node hyperplasia with progressively transformed germinal centers, presence of clonal immunoglobulin gene rearrangements with somatic hypermutations and ongoing mutations, and relation with a number of inherited defects affecting the immune system, it has been suspected that NLPHL might be antigen-driven. Recent evidence has shown that cases of IgD-positive NLPHL are associated with infection by Moraxella catarrhalis, a common bacterium in the upper respiratory tract and in lymph nodes. This review summarizes the evidence for NLPHL as a B-cell lymphoma involving follicular T-lymphocytes normally found in germinal centers, its molecular features and relation to inherited immune defects, and its relation and differential diagnosis from similar entities. Finally, it discusses the evidence that in many cases a watch and wait policy might be a viable initial management strategy. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Antígenos de Neoplasias/imunologia , Linfócitos B/imunologia , Doença de Hodgkin/imunologia , Moraxella catarrhalis/imunologia , Infecções por Moraxellaceae/imunologia , Linfócitos T/imunologia , Antígenos de Neoplasias/genética , Linfócitos B/microbiologia , Doença de Hodgkin/genética , Doença de Hodgkin/microbiologia , Doença de Hodgkin/terapia , Humanos , Moraxella catarrhalis/patogenicidade , Infecções por Moraxellaceae/microbiologia , Fenótipo , Prognóstico , Linfócitos T/microbiologia , Microambiente Tumoral
12.
Inorg Chem ; 60(1): 28-31, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33332970

RESUMO

We report on the new monosubstituted aluminum Keggin-type germanotungstate (C4H12N)4[HAlGeW11O39(H2O)]·11H2O ([Al(H2O)GeW11]4-), which has been synthesized at room temperature via rearrangement of the dilacunary [γ-GeW10O36]8- polyoxometalate precursor. [Al(H2O)GeW11]4- has been characterized thoroughly both in the solid state by single-crystal and powder X-ray diffraction, IR spectroscopy, thermogravimetric analysis, and elemental analysis as well as in solution by cyclic voltammetry (CV) 183W, 27Al NMR and UV-vis spectroscopy. A study on the antibacterial properties of [Al(H2O)GeW11]4- and the known aluminum(III)-centered Keggin polyoxotungstates (Al-POTs) α-Na5[AlW12O40] (α-[AlW12O40]5-) and Na6[Al(AlOH2)W11O39] ([Al(AlOH2)W11O39]6-) revealed enhanced activity for all three Al-POTs against the Gram-negative bacterium Moraxella catarrhalis (minimum inhibitory concentration (MIC) up to 4 µg mL-1) and the Gram-positive Enterococcus faecalis (MIC up to 128 µg mL-1) compared to the inactive Al(NO3)3 salt (MIC > 256 µg mL-1). CV indicates the redox activity of the Al-POTs as a dominating factor for the observed antibacterial activity with increased tendency to reduction, resulting in increased antibacterial activity of the POT.


Assuntos
Alumínio/farmacologia , Antibacterianos/farmacologia , Complexos de Coordenação/farmacologia , Enterococcus faecalis/efeitos dos fármacos , Germânio/farmacologia , Moraxella catarrhalis/efeitos dos fármacos , Tungstênio/farmacologia , Alumínio/química , Antibacterianos/síntese química , Antibacterianos/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Germânio/química , Testes de Sensibilidade Microbiana , Tungstênio/química
13.
Ann Lab Med ; 41(3): 293-301, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33303714

RESUMO

Background: Tigecycline, eravacycline, and omadacycline are recently developed tetracyclines. Susceptibility of microbes to these tetracyclines and their molecular mechanisms have not been well elucidated. We investigated the susceptibility of Moraxella catarrhalis to tigecycline, eravacycline, and omadacycline and its resistance mechanisms against these tetracyclines. Methods: A total of 207 non-duplicate M. catarrhalis isolates were collected from different inpatients. The minimum inhibitory concentrations (MICs) of the tetracyclines were determined by broth microdilution. Tigecycline-, eravacycline-, or omadacycline-resistant isolates were induced under in vitro pressure. The tet genes and mutations in the 16S rRNA was detected by PCR and sequencing. Results: Eravacycline had a lower MIC50 (0.06 mg/L) than tigecycline (0.125 mg/L) or omadacycline (0.125 mg/L) against M. catarrhalis isolates. We found that 136 isolates (65.7%) had the tetB gene, and 15 (7.2%) isolates were positive for tetL; however, their presence was not correlated with high tigecycline, eravacycline, or omadacycline (≥1 mg/L) MICs. Compared with the initial MIC after 160 days of induction, the MICs of tigecycline or eravacycline against three M. catarrhalis isolates increased ≥eight-fold, while those of omadacycline against two M. catarrhalis isolates increased 64-fold. Mutations in the 16S rRNA genes (C1036T and/or G460A) were observed in omadacycline-induced resistant isolates, and increased RR (the genes encoding 16SrRNA (four copies, RR1-RR4) copy number of 16S rRNA genes with mutations was associated with increased resistance to omadacycline. Conclusions: Tigecycline, eravacycline, and omadacycline exhibited robust antimicrobial effects against M. catarrhalis. Mutations in the 16S rRNA genes contributed to omadacycline resistance in M. catarrhalis.


Assuntos
Moraxella catarrhalis , Tetraciclinas , Antibacterianos/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , RNA Ribossômico 16S , Tigeciclina
14.
PLoS One ; 15(12): e0243942, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33306743

RESUMO

Some children are more susceptible to viral and bacterial respiratory infections in the first few years of life than others. However, the factors contributing to this susceptibility are incompletely understood. In a retrospective analysis of clinical samples collected from a prospectively-enrolled cohort of 358 children we sought associations between physician-attended illness visits and bacterial colonization in the first five years of life. A subset of children was identified by unsupervised clustering analysis as infection and allergy prone (IAP). Several respiratory infection- and allergy-mediated illnesses co-occurred at higher rates in IAP children, while the rates of other illnesses were not significantly different between the groups. Analyses of nasopharyngeal (NP) pathobionts and microbiota commensals showed that early age of first colonization with pathobionts Streptococcus pneumonia, non-typeable Haemophilus influenzae, and Moraxella catarrhalis was associated with IAP children, and particularly Moraxella abundance was negatively associated with NP microbiome diversity. We conclude that mucosal pathobiont exposures in early life can influence susceptibility to respiratory illnesses in children.


Assuntos
Portador Sadio/epidemiologia , Doenças Nasofaríngeas/epidemiologia , Pneumonia Pneumocócica/epidemiologia , Infecções Respiratórias/epidemiologia , Portador Sadio/microbiologia , Criança , Pré-Escolar , Feminino , Haemophilus influenzae/isolamento & purificação , Haemophilus influenzae/patogenicidade , Humanos , Lactente , Masculino , Microbiota , Moraxella catarrhalis/isolamento & purificação , Moraxella catarrhalis/patogenicidade , Doenças Nasofaríngeas/microbiologia , Nasofaringe/microbiologia , Nasofaringe/patologia , Pneumonia Pneumocócica/microbiologia , Infecções Respiratórias/microbiologia , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/patogenicidade , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/patogenicidade
15.
J Interferon Cytokine Res ; 40(12): 555-569, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33337936

RESUMO

Secretory otitis media (SOM) is characterized by persistence of fluid in the middle ear, often following an episode of acute otitis media. Our hypothesis is that failure to eliminate bacterial or viral pathogens may result in persistent low-grade inflammation. In this study, we analyzed inflammatory mediators in middle ear fluids from 67 children with SOM. This was combined with determinations of viable bacteria by culture along with detection of bacterial and viral genetic material by real-time polymerase chain reaction (PCR). The inflammatory mediators found at the highest concentrations (>30 ng/mL) were stem cell growth factor-ß (median 110 ng/mL), CXCL1, IL-16, IL-8, migration inhibitory factor, CXCL10, and CXCL9. Among bacterial pathogens, Moraxella catarrhalis and Haemophilus influenzae dominated, regardless of detection methods, while rhinovirus dominated among viral pathogens. Middle ear fluid levels of interleukin (IL)-1α, IL-17, IL-1ß, fibroblast growth factor basic, and tumor necrosis factor correlated strongly with presence of bacteria detected either by culture or PCR, while IL-1RA, IL-3, IL-6, IL-8, CCL3, CCL4, and granulocyte-colony stimulating factor correlated significantly with real-time PCR values. CXCL10, CXCL9, CCL2, and TRAIL correlated significantly with viral nucleic acid levels. To conclude, persistence of viral and bacterial pathogens may fuel persistent inflammation in SOM. Bacteria caused a broad inflammatory response, while viruses chiefly elicited the interferon-induced chemokines CXCL9 and CXCL10.


Assuntos
Haemophilus influenzae/imunologia , Mediadores da Inflamação/imunologia , Moraxella catarrhalis/imunologia , Ácidos Nucleicos/imunologia , Otite Média com Derrame/imunologia , Rhinovirus/imunologia , Líquidos Corporais/imunologia , Líquidos Corporais/microbiologia , Líquidos Corporais/virologia , Criança , Pré-Escolar , Citocinas/genética , Citocinas/imunologia , Orelha Média/imunologia , Orelha Média/microbiologia , Orelha Média/virologia , Feminino , Humanos , Lactente , Masculino , Ácidos Nucleicos/genética , Otite Média com Derrame/microbiologia , Otite Média com Derrame/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
BMC Infect Dis ; 20(1): 821, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172398

RESUMO

BACKGROUND: Although Moraxella catarrhalis (M. catarrhalis) is a common cause of community-acquired pneumonia (CAP), studies investigating clinical manifestations of CAP due to M. catarrhalis (MC-CAP) in adults are limited. Since S. pneumoniae is the leading cause of CAP globally, it is important to distinguish between MC-CAP and CAP due to S. pneumoniae (SP-CAP) in clinical practice. However, no past study compared clinical characteristics of MC-CAP and SP-CAP by statistical analysis. We aimed to clarify the clinical characteristics of MC-CAP by comparing those of SP-CAP, as well as the utility of sputum Gram staining. METHODS: This retrospective study screened CAP patients aged over 20 years visiting or admitted to Okinawa Miyako Hospital between May 2013 and April 2018. Among these, we included patients whom either M. catarrhalis alone or S. pneumoniae alone was isolated from their sputum by bacterial cultures. RESULTS: We identified 134 MC-CAP and 130 SP-CAP patients. Although seasonality was not observed in SP-CAP, almost half of MC-CAP patients were admitted in the winter. Compared to those with SP-CAP, MC-CAP patients were older (p < 0.01) and more likely to have underlying pulmonary diseases such as asthma and bronchiectasis (p < 0.01). Approximately half of asthmatic MC-CAP and SP-CAP patients had asthma attacks. Although winter is an influenza season in Japan, co-infection with influenza virus was less common in MC-CAP compared to SP-CAP patients (3% vs. 15%, p < 0.01). Bronchopneumonia patterns on X-ray, as well as bronchial wall thickening, bilateral distribution, and segmental pattern on CT were more common in MC-CAP patients than in SP-CAP patients (p < 0.01). Sputum Gram stain was highly useful method for the diagnosis in both MC-CAP and SP-CAP (78.4% vs. 89.2%), and penicillins were most frequently chosen as an initial treatment for both pneumonias. CONCLUSIONS: This is the first study to show that MC-CAP occurred in older people compared to SP-CAP, influenza virus co-infection was less common in MC-CAP than SP-CAP, and that MC-CAP frequently caused asthma attacks. Gram stain contributed for the appropriate treatment, resulting in conserving broad-spectrum antibiotics such as cephalosporins and fluoroquinolones in both MC-CAP and SP-CAP patients.


Assuntos
Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Moraxella catarrhalis/isolamento & purificação , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , Streptococcus pneumoniae/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Violeta Genciana , Hospitalização , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Fenazinas , Pneumonia/microbiologia , Estudos Retrospectivos , Escarro/microbiologia , Coloração e Rotulagem , Resultado do Tratamento , Adulto Jovem
17.
BMC Res Notes ; 13(1): 547, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239090

RESUMO

OBJECTIVE: Moraxella catarrhalis is a non-motile Gram-negative diplococcus bacterium that contributed to several human infections including conjunctivitis. This study aimed to reveal the prevalence of M. catarrhalis in patients who suffered from conjunctivitis in Ahvaz city, southwest of Iran. RESULTS: Out of 100 conjunctiva swab specimens, M. catarrhalis was isolated only from one (1%) conjunctivitis cases using the culture method. This strain was isolated from a 34 years old female patient. Also, the results of the polymerase chain reaction (PCR) were in agreement with the culture method, and the specimen that showed positive culture was also positive for specific gene of M. catarrhalis. The remaining 99 specimens did not show positive results with any of the culture and PCR methods.


Assuntos
Conjuntivite , Infecções por Moraxellaceae , Adulto , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Moraxella catarrhalis , Infecções por Moraxellaceae/epidemiologia , Prevalência
18.
Protein J ; 39(5): 449-460, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33037984

RESUMO

Chorismate serves as a crucial precursor for the synthesis of many aromatic compounds essential for the survival and virulence in various bacteria and protozoans. Chorismate synthase, a vital enzyme in the shikimate pathway, is responsible for the formation of chorismate from enolpyruvylshikimate-3-phosphate (EPSP). Moraxella catarrhalis is reported to be resistant to many beta-lactam antibiotics and causes chronic ailments such as otitis media, sinusitis, laryngitis, and bronchopulmonary infections. Here, we have cloned the aroC gene from Moraxella catarrhalis in pET28c and heterologously produced the chorismate synthase (~ 43 kDa) in Escherichia coli BL21(DE3) cells. We have predicted the three-dimensional structure of this enzyme and used the refined model for ligand-based virtual screening against Supernatural Database using PyRx tool that led to the identification of the top three molecules (caffeic acid, gallic acid, and o-coumaric acid). The resultant protein-ligand complex structures were subjected to 50 ns molecular dynamics (MD) simulation using GROMACS. Further, the binding energy was calculated by MM/PBSA approach using the trajectory obtained from MD simulation. The binding affinities of these compounds were validated with ITC experiments, which suggest that gallic acid has the highest binding affinity amongst these three phytochemicals. Together, these results pave the way for the use of these phytochemicals as potential anti-bacterial compounds.


Assuntos
Antibacterianos/química , Proteínas de Bactérias , Simulação por Computador , Sistemas de Liberação de Medicamentos , Farmacorresistência Bacteriana , Simulação de Dinâmica Molecular , Moraxella catarrhalis/enzimologia , Fósforo-Oxigênio Liases , Compostos Fitoquímicos/química , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/química , Humanos , Fósforo-Oxigênio Liases/antagonistas & inibidores , Fósforo-Oxigênio Liases/química
19.
Front Immunol ; 11: 2122, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983170

RESUMO

Moraxella catarrhalis is a human-specific commensal of the respiratory tract and an opportunistic pathogen. It is one of the leading cause of otitis media in children and of acute exacerbations in patients with chronic obstructive pulmonary disease, resulting in significant morbidity and economic burden. Vaccines and new immunotherapeutic strategies to treat this emerging pathogen are needed. Complement is a key component of innate immunity that mediates the detection, response, and subsequent elimination of invading pathogens. Many pathogens including M. catarrhalis have evolved complement evasion mechanisms, which include the binding of human complement inhibitors such as C4b-binding protein (C4BP) and Factor H (FH). Inhibiting C4BP and FH acquisition by M. catarrhalis may provide a novel therapeutic avenue to treat infections. To achieve this, we created two chimeric proteins that combined the Moraxella-binding domains of C4BP and FH fused to human immunoglobulin Fcs: C4BP domains 1 and 2 and FH domains 6 and 7 fused to IgM and IgG Fc, respectively. As expected, FH6-7/IgG displaced FH from the bacterial surface while simultaneously activating complement via Fc-C1q interactions, together increasing pathogen elimination. C4BP1-2/IgM also increased serum killing of the bacteria through enhanced complement deposition, but did not displace C4BP from the surface of M. catarrhalis. These Fc fusion proteins could act as anti-infective immunotherapies. Many microbes bind the complement inhibitors C4BP and FH through the same domains as M. catarrhalis, therefore these Fc fusion proteins may be promising candidates as adjunctive therapy against many different drug-resistant pathogens.


Assuntos
Proteína de Ligação ao Complemento C4b/farmacologia , Fator H do Complemento/farmacologia , Fragmentos Fc das Imunoglobulinas/farmacologia , Moraxella catarrhalis/efeitos dos fármacos , Proteínas Recombinantes de Fusão/farmacologia , Animais , Ligação Competitiva , Atividade Bactericida do Sangue , Células CHO , Complemento C3b/análise , Complemento C3d/análise , Proteína de Ligação ao Complemento C4b/genética , Proteína de Ligação ao Complemento C4b/metabolismo , Fator H do Complemento/genética , Fator H do Complemento/metabolismo , Cricetinae , Cricetulus , Humanos , Fragmentos Fc das Imunoglobulinas/genética , Imunoglobulina G/genética , Imunoglobulina G/metabolismo , Imunoglobulina G/farmacologia , Imunoglobulina M/genética , Imunoglobulina M/metabolismo , Imunoglobulina M/farmacologia , Moraxella catarrhalis/metabolismo , Ligação Proteica , Domínios Proteicos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo
20.
Drug Dev Ind Pharm ; 46(9): 1517-1523, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32808581

RESUMO

Branched oligohexamethyleneguanidine hydrochloride (OHMG) possesses great potential for the development of novel drugs for the treatment of diseases caused by bacteria. This study aimed at evaluating the antimicrobial activity of OHMG against potential causative agents of oral and pharyngeal mucosa infections, specifically, the activity against 56 clinical strains, 5 of which were antibiotics-resistant. Also, a preliminary in vivo study of the specific activity of OHMG based on a traumatic stomatitis and gingivitis model in rabbits was carried out. In vitro antimicrobial activity of OHMG was determined by testing the minimal inhibitory concentration (MIC). OHMG displayed excellent activity against Streptococcus pneumoniae, Streptococcus pyogenes (MIC was 0.002-0.25 µg/ml), Moraxella catarrhalis (0.03-0.06 µg/ml), Neisseria gonorrhoeae (0.125-2 µg/ml). Almost complete healing of defects in the groups of animals within the 7-day application of 'OHMG hydrochloride' at concentrations of 0.1% and 0.3% after the thermal formation of the stomatitis and gingivitis model was observed.


Assuntos
Antibacterianos/farmacologia , Guanidina/farmacologia , Haemophilus influenzae , Moraxella catarrhalis , Streptococcus pneumoniae/química , Animais , Antibacterianos/química , Antibacterianos/uso terapêutico , Guanidina/análogos & derivados , Guanidina/química , Testes de Sensibilidade Microbiana , Coelhos
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