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1.
Respir Res ; 25(1): 173, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643126

RESUMO

RATIONALE: Our understanding of airway dysbiosis in chronic obstructive pulmonary disease (COPD) remains incomplete, which may be improved by unraveling the complexity in microbial interactome. OBJECTIVES: To characterize reproducible features of airway bacterial interactome in COPD at clinical stability and during exacerbation, and evaluate their associations with disease phenotypes. METHODS: We performed weighted ensemble-based co-occurrence network analysis of 1742 sputum microbiomes from published and new microbiome datasets, comprising two case-control studies of stable COPD versus healthy control, two studies of COPD stability versus exacerbation, and one study with exacerbation-recovery time series data. RESULTS: Patients with COPD had reproducibly lower degree of negative bacterial interactions, i.e. total number of negative interactions as a proportion of total interactions, in their airway microbiome compared with healthy controls. Evaluation of the Haemophilus interactome showed that the antagonistic interaction networks of this established pathogen rather than its abundance consistently changed in COPD. Interactome dynamic analysis revealed reproducibly reduced antagonistic interactions but not diversity loss during COPD exacerbation, which recovered after treatment. In phenotypic analysis, unsupervised network clustering showed that loss of antagonistic interactions was associated with worse clinical symptoms (dyspnea), poorer lung function, exaggerated neutrophilic inflammation, and higher exacerbation risk. Furthermore, the frequent exacerbators (≥ 2 exacerbations per year) had significantly reduced antagonistic bacterial interactions while exhibiting subtle compositional changes in their airway microbiota. CONCLUSIONS: Bacterial interactome disturbance characterized by reduced antagonistic interactions, rather than change in pathogen abundance or diversity, is a reproducible feature of airway dysbiosis in COPD clinical stability and exacerbations, which suggests that we may target interactome rather than pathogen alone for disease treatment.


Assuntos
Disbiose , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pulmão , Haemophilus , Escarro/microbiologia , Progressão da Doença
2.
Microbiol Spectr ; 12(4): e0401723, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38488280

RESUMO

Haemophilus and Aggregatibacter are two of the most common bacterial genera in the human oral cavity, encompassing both commensals and pathogens of substantial ecological and medical significance. In this study, we conducted a metapangenomic analysis of oral Haemophilus and Aggregatibacter species to uncover genomic diversity, phylogenetic relationships, and habitat specialization within the human oral cavity. Using three metrics-pangenomic gene content, phylogenomics, and average nucleotide identity (ANI)-we first identified distinct species and sub-species groups among these genera. Mapping of metagenomic reads then revealed clear patterns of habitat specialization, such as Aggregatibacter species predominantly in dental plaque, a distinctive Haemophilus parainfluenzae sub-species group on the tongue dorsum, and H. sp. HMT-036 predominantly in keratinized gingiva and buccal mucosa. In addition, we found that supragingival plaque samples contained predominantly only one out of the three taxa, H. parainfluenzae, Aggregatibacter aphrophilus, and A. sp. HMT-458, suggesting independent niches or a competitive relationship. Functional analyses revealed the presence of key metabolic genes, such as oxaloacetate decarboxylase, correlated with habitat specialization, suggesting metabolic versatility as a driving force. Additionally, heme synthesis distinguishes H. sp. HMT-036 from closely related Haemophilus haemolyticus, suggesting that the availability of micronutrients, particularly iron, was important in the evolutionary ecology of these species. Overall, our study exemplifies the power of metapangenomics to identify factors that may affect ecological interactions within microbial communities, including genomic diversity, habitat specialization, and metabolic versatility. IMPORTANCE: Understanding the microbial ecology of the mouth is essential for comprehending human physiology. This study employs metapangenomics to reveal that various Haemophilus and Aggregatibacter species exhibit distinct ecological preferences within the oral cavity of healthy individuals, thereby supporting the site-specialist hypothesis. Additionally, it was observed that the gene pool of different Haemophilus species correlates with their ecological niches. These findings shed light on the significance of key metabolic functions in shaping microbial distribution patterns and interspecies interactions in the oral ecosystem.


Assuntos
Ecossistema , Haemophilus , Humanos , Aggregatibacter/fisiologia , Filogenia , Haemophilus/genética , Boca
3.
Respir Res ; 25(1): 130, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500160

RESUMO

RATIONALE: The lung microbiome is an inflammatory stimulus whose role in the development of lung malignancies is incompletely understood. We hypothesized that the lung microbiome associates with multiple clinical factors, including the presence of a lung malignancy. OBJECTIVES: To assess associations between the upper and lower airway microbiome and multiple clinical factors including lung malignancy. METHODS: We conducted a prospective cohort study of upper and lower airway microbiome samples from 44 subjects undergoing lung lobectomy for suspected or confirmed lung cancer. Subjects provided oral (2), induced sputum, nasopharyngeal, bronchial, and lung tissue (3) samples. Pathologic diagnosis, age, tobacco use, dental care history, lung function, and inhaled corticosteroid use were associated with upper and lower airway microbiome findings. MEASUREMENTS AND MAIN RESULTS: Older age was associated with greater Simpson diversity in the oral and nasopharyngeal sites (p = 0.022 and p = 0.019, respectively). Current tobacco use was associated with greater lung and bronchus Simpson diversity (p < 0.0001). Self-reported last profession dental cleaning more than 6 months prior (vs. 6 or fewer months prior) was associated with lower lung and bronchus Simpson diversity (p < 0.0001). Diagnosis of a lung adenocarcinoma (vs. other pathologic findings) was associated with lower bronchus and lung Simpson diversity (p = 0.024). Last professional dental cleaning, dichotomized as ≤ 6 months vs. >6 months prior, was associated with clustering among lung samples (p = 0.027, R2 = 0.016). Current tobacco use was associated with greater abundance of pulmonary pathogens Mycoplasmoides and Haemophilus in lower airway samples. Self-reported professional dental cleaning ≤ 6 months prior (vs. >6 months prior) was associated with greater bronchial Actinomyces and lung Streptococcus abundance. Lung adenocarcinoma (vs. no lung adenocarcinoma) was associated with lower Lawsonella abundance in lung samples. Inhaled corticosteroid use was associated with greater abundance of Haemophilus among oral samples and greater Staphylococcus among lung samples. CONCLUSIONS: Current tobacco use, recent dental cleaning, and a diagnosis of adenocarcinoma are associated with lung and bronchial microbiome α-diversity, composition (ß-diversity), and the abundance of several respiratory pathogens. These findings suggest that modifiable habits (tobacco use and dental care) may influence the lower airway microbiome. Larger controlled studies to investigate these potential associations are warranted.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Microbiota , Humanos , Estudos Prospectivos , Autorrelato , Pulmão/patologia , Brônquios/patologia , Adenocarcinoma de Pulmão/diagnóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Haemophilus , Uso de Tabaco/efeitos adversos , Uso de Tabaco/epidemiologia , Hábitos , Corticosteroides
4.
mSphere ; 9(3): e0000624, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38380941

RESUMO

Iron acquisition is a key feature dictating the success of pathogen colonization and infection. Pathogens scavenging iron from the host must contend with other members of the microbiome similarly competing for the limited pool of bioavailable iron, often in the form of heme. In this study, we identify a beneficial role for the heme-binding protein hemophilin (Hpl) produced by the non-pathogenic bacterium Haemophilus haemolyticus against its close relative, the opportunistic respiratory tract pathogen non-typeable Haemophilus influenzae (NTHi). Using a mouse model, we found that pre-exposure to H. haemolyticus significantly reduced NTHi colonization of the upper airway and impaired NTHi infection of the lungs in an Hpl-dependent manner. Further, treatment with recombinant Hpl was sufficient to decrease airway burdens of NTHi without exacerbating lung immunopathology or systemic inflammation. Instead, mucosal production of the neutrophil chemokine CXCL2, lung myeloperoxidase, and serum pro-inflammatory cytokines IL-6 and TNFα were lower in Hpl-treated mice. Mechanistically, H. haemolyticus suppressed NTHi growth and adherence to human respiratory tract epithelial cells through the expression of Hpl, and recombinant Hpl could recapitulate these effects. Together, these findings indicate that heme sequestration by non-pathogenic, Hpl-producing H. haemolyticus is protective against NTHi colonization and infection. IMPORTANCE: The microbiome provides a critical layer of protection against infection with bacterial pathogens. This protection is accomplished through a variety of mechanisms, including interference with pathogen growth and adherence to host cells. In terms of immune defense, another way to prevent pathogens from establishing infections is by limiting the availability of nutrients, referred to as nutritional immunity. Restricting pathogen access to iron is a central component of this approach. Here, we uncovered an example where these two strategies intersect to impede infection with the respiratory tract bacterial pathogen Haemophilus influenzae. Specifically, we find that a non-pathogenic (commensal) bacterium closely related to H. influenzae called Haemophilus haemolyticus improves protection against H. influenzae by limiting the ability of this pathogen to access iron. These findings suggest that beneficial members of the microbiome improve protection against pathogen infection by effectively contributing to host nutritional immunity.


Assuntos
Infecções por Haemophilus , Haemophilus influenzae , Haemophilus , Humanos , Heme/metabolismo , Pulmão/microbiologia , Ferro
5.
Rev. int. androl. (Internet) ; 21(4): 1-9, oct.-dic. 2023. tab
Artigo em Espanhol | IBECS | ID: ibc-225997

RESUMO

Introducción: Con el avance de los métodos microbiológicos, cada vez es más frecuente el aislamiento de patógenos menos típicos en cuadros de infección uretral y rectal, además de los agentes etiológicos clásicos. Uno de ellos está formado por especies de Haemophilus no ducreyi (HND). El objetivo de este trabajo es describir la frecuencia, la sensibilidad antibiótica y las características clínicas de las uretritis y proctitis por HND en varones. Pacientes y métodos: Se realizó un estudio observacional descriptivo y retrospectivo, a partir de los resultados emitidos por el Laboratorio de Microbiología del Hospital Universitario Virgen de las Nieves de Granada, de los aislamientos, entre 2016 y 2019, de HND en episodios infecciosos genitales y rectales de varones adultos. Resultados: Se aisló HND en 135 (7%) episodios. La especie más frecuente fue H. parainfluenzae (34/45; 75,6%). Los síntomas más frecuentes de las proctitis fueron: tenesmo rectal (31,6%) y adenopatías (10,5%); en aquellos con uretritis, fueron disuria (71,6%), supuración uretral (46,7%) y lesiones en el glande (27%), siendo manifestaciones similares a las infecciones provocadas por los genitopatógenos habituales. Un 43% de los pacientes eran VIH positivos. Las tasas de resistencia a antibióticos de H. parainfluenzae fueron elevadas a levofloxacino, ampicilina, tetraciclina y azitromicina. Conclusión: Las especies de HND deberían tenerse en cuenta como posibles agentes etiológicos en episodios de infección uretral y rectal en varones, sobre todo en los casos con pruebas de detección negativas para agentes productores habituales de infecciones de transmisión sexual. Su detección microbiológica es fundamental para la instauración de un tratamiento efectivo dirigido. (AU)


Introduction: With the advancement of microbiological methods, the isolation of less typical pathogens in cases of urethral and rectal infection is more frequent, apart from the classic etiological agents. One of them is formed by species of Haemophilus no ducreyi (HND). The objective of this work is to describe frequency, susceptibility to antibiotics, and clinical features of HDN urethritis and proctitis in adult males. Patients and methods: This is an observational retrospective descriptive study of the results obtained by the Microbiology laboratory of the Virgen de las Nieves University Hospital on the isolates of HND in genital and rectal samples from males between 2016 and 2019. Results: HND was isolated in 135 (7%) of the genital infection episodes diagnosed in men. H. parainfluenzae was the most commonly isolated (34/45; 75.6%). The most frequent symptoms in men with proctitis were rectal tenesmus (31.6%) and lymphadenopathy (10.5%); in those with urethritis, dysuria (71.6%), urethral suppuration (46.7%) and gland lesions (27%), so differentiating it from infections caused by other genitopathogens is difficult. 43% of patients were HIV positive. Antibiotic resistance rates for H. parainfluenzae were high to quinolons, ampicillin, tetracycline and macrolides. Conclusion: HND species should be considered as possible etiologic agents in episodes of urethral and rectal infection in men, especially in cases with negative screening tests for agents that cause sexually transmitted infections (STIs). Its microbiological identification is essential for the establishment of an effective targeted treatment. (AU)


Assuntos
Humanos , Masculino , Adulto , Haemophilus , Uretrite , Proctite , Infecções do Sistema Genital , Epidemiologia Descritiva , Estudos Retrospectivos , Espanha
6.
Respir Res ; 24(1): 264, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37919749

RESUMO

The prevalence and clinical correlates of antibiotic resistance genes (ARGs) in bronchiectasis are not entirely clear. We aimed to profile the ARGs in sputum from adults with bronchiectasis, and explore the association with airway microbiome and disease severity and subtypes. In this longitudinal study, we prospectively collected 118 sputum samples from stable and exacerbation visits of 82 bronchiectasis patients and 19 healthy subjects. We profiled ARGs with shotgun metagenomic sequencing, and linked these to sputum microbiome and clinical characteristics, followed by validation in an international cohort. We compared ARG profiles in bronchiectasis according to disease severity, blood and sputum inflammatory subtypes. Unsupervised clustering revealed a Pseudomonas predominant subgroup (n = 16), Haemophilus predominant subgroup (n = 48), and balanced microbiome subgroup (N = 54). ARGs of multi-drug resistance were over-dominant in the Pseudomonas-predominant subgroup, while ARGs of beta-lactam resistance were most abundant in the Haemophilus-predominant subgroup. Pseudomonas-predominant subgroup yielded the highest ARG diversity and total abundance, while Haemophilus-predominant subgroup and balanced microbiota subgroup were lowest in ARG diversity and total abundance. PBP-1A, ksgA and emrB (multidrug) were most significantly enriched in Haemophilus-predominant subtype. ARGs generally correlated positively with Bronchiectasis Severity Index, fluoroquinolone use, and modified Reiff score. 68.6% of the ARG-clinical correlations could be validated in an independent international cohort. In conclusion, ARGs are differentially associated with the dominant microbiome and clinical characteristics in bronchiectasis.


Assuntos
Bronquiectasia , Haemophilus , Adulto , Humanos , Pseudomonas , Estudos Longitudinais , Bronquiectasia/diagnóstico , Bronquiectasia/genética , Sistema Respiratório , Antibacterianos/uso terapêutico
7.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 41(8): 468-484, oct. 2023. tab
Artigo em Espanhol | IBECS | ID: ibc-226405

RESUMO

Introducción y objetivos Actualmente el diagnóstico microbiológico de las infecciones genitales se realiza con métodos moleculares, los cuales permiten detectar agentes etiológicos menos frecuentes, pero con potencial importancia patogénica, como Haemophilus spp. El objetivo de esta revisión es analizar y resaltar la importancia clínica del aislamiento de Haemophilus spp. en infecciones genitales y rectales, excluyendo H. ducreyi. Material y métodos Se ha realizado una revisión sistemática en base a una búsqueda exhaustiva de las publicaciones incluidas en la base de datos MEDLINE hasta el 5 de agosto de 2021, sobre la presencia de Haemophilus spp. en infecciones genitales y rectales, excluyendo H. ducreyi. Resultados Tras revisar lo descrito en la literatura, las especies de Haemophilus (excluyendo H. ducreyi: HSNOD) se detectaron en 2397 episodios de infección genital, siendo las especies más frecuentemente aisladas H. influenzae y H. parainfluenzae. La mayoría de los episodios (87,6%) están constituidos por aislamiento único. Existe un ligero predominio en mujeres (48,3%) donde puede producir cuadros de vaginitis, salpingitis, endometritis o complicaciones durante el embarazo. En hombres, el cuadro clínico suele corresponder a una uretritis. La mayoría de las muestras corresponde a exudados vaginales y uretrales, con una representación minoritaria a nivel rectal (2,3%). Conclusión HSNOD desempeña un papel patogénico relevante en episodios de infección genital, por lo que los protocolos de diagnóstico microbiológico deben incluir métodos que permitan su detección, así como incluirlos en el espectro etiológico de este tipo de cuadros clínicos (AU)


Introduction and objectives Currently, the microbiological diagnosis of genital infections is carried out with molecular methods, which allow the detection of less frequent etiological agents but with potential pathogenic importance, such as Haemophilus spp. The objective of this review is to analyze and highlight the clinical importance of the isolation of Haemophilus spp. in genital and rectal infections, excluding H. ducreyi. Material and methods A systematic review was carried out based on an exhaustive search of the publications included in the MEDLINE database up to August 5, 2021, on the presence of Haemophilus spp. in genital and rectal infections, excluding H. ducreyi. Results After reviewing what was described in the literature, Haemophilus spp. (excluding H. ducreyi: HSNOD) was detected in 2397 episodes of genital infection, the most frequently isolated species being H. influenzae and H. parainfluenzae. Most of the episodes (87.6%) are constituted by single isolation. There is a slight predominance in women (48.3%) where it can cause vaginitis, salpingitis, endometritis or complications during pregnancy. In men, the clinical picture usually corresponds to urethritis. Most of the samples correspond to vaginal and urethral exudates, with a minority representation at the rectal level (2.3%). Conclusion HSNOD plays a relevant pathogenic role in episodes of genital infection, so microbiological diagnostic protocols must include methods that allow their detection, as well as include them in the etiological spectrum of this type of clinical picture (AU)


Assuntos
Humanos , Masculino , Feminino , Doenças Virais Sexualmente Transmissíveis/virologia , Vulvovaginite/virologia , Uretrite/virologia , Proctite/virologia , Haemophilus/isolamento & purificação , Infecções por Haemophilus/virologia
8.
Rev Int Androl ; 21(4): 100374, 2023.
Artigo em Espanhol | MEDLINE | ID: mdl-37413940

RESUMO

INTRODUCTION: With the advancement of microbiological methods, the isolation of less typical pathogens in cases of urethral and rectal infection is more frequent, apart from the classic etiological agents. One of them is formed by species of Haemophilus no ducreyi (HND). The objective of this work is to describe frequency, susceptibility to antibiotics, and clinical features of HDN urethritis and proctitis in adult males. PATIENTS AND METHODS: This is an observational retrospective descriptive study of the results obtained by the Microbiology laboratory of the Virgen de las Nieves University Hospital on the isolates of HND in genital and rectal samples from males between 2016 and 2019. RESULTS: HND was isolated in 135 (7%) of the genital infection episodes diagnosed in men. H. parainfluenzae was the most commonly isolated (34/45; 75.6%). The most frequent symptoms in men with proctitis were rectal tenesmus (31.6%) and lymphadenopathy (10.5%); in those with urethritis, dysuria (71.6%), urethral suppuration (46.7%) and gland lesions (27%), so differentiating it from infections caused by other genitopathogens is difficult. 43% of patients were HIV positive. Antibiotic resistance rates for H. parainfluenzae were high to quinolons, ampicillin, tetracycline and macrolides. CONCLUSION: HND species should be considered as possible etiologic agents in episodes of urethral and rectal infection in men, especially in cases with negative screening tests for agents that cause sexually transmitted infections (STIs). Its microbiological identification is essential for the establishment of an effective targeted treatment.


Assuntos
Haemophilus ducreyi , Proctite , Uretrite , Masculino , Adulto , Humanos , Uretrite/tratamento farmacológico , Estudos Retrospectivos , Haemophilus , Uretra/microbiologia
9.
Microbiol Spectr ; 11(4): e0477222, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37382545

RESUMO

Haemophilus seminalis is a newly proposed species that is phylogenetically related to Haemophilus haemolyticus. The distribution of H. seminalis in the human population, its genomic diversity, and its pathogenic potential are still unclear. This study reports the finding of our comparative genomic analyses of four newly isolated Haemophilus strains (SZY H8, SZY H35, SZY H36, and SZY H68) from human sputum specimens (Guangzhou, China) along with the publicly available genomes of other phylogenetically related Haemophilus species. Based on pairwise comparisons of the 16S rRNA gene sequences, the four isolates showed <98.65% sequence identity to the type strains of all known Haemophilus species but were identified as belonging to H. seminalis, based on comparable phenotypic and genotypic features. Additionally, the four isolates showed high genome-genome relatedness indices (>95% ANI values) with 17 strains that were previously identified as either "Haemophilus intermedius" or hemin (X-factor)-independent H. haemolyticus and therefore required a more detailed classification study. Phylogenetically, these isolates, along with the two previously described H. seminalis isolates (a total of 23 isolates), shared a highly homologous lineage that is distinct from the clades of the main H. haemolyticus and Haemophilus influenzae strains. These isolates present an open pangenome with multiple virulence genes. Notably, all 23 isolates have a functional heme biosynthesis pathway that is similar to that of Haemophilus parainfluenzae. The phenotype of hemin (X-factor) independence and the analysis of the ispD, pepG, and moeA genes can be used to distinguish these isolates from H. haemolyticus and H. influenzae. Based on the above findings, we propose a reclassification for all "H. intermedius" and two H. haemolyticus isolates belonging to H. seminalis with an emended description of H. seminalis. This study provides a more accurate identification of Haemophilus isolates for use in the clinical laboratory and a better understanding of the clinical significance and genetic diversity in human environments. IMPORTANCE As a versatile opportunistic pathogen, the accurate identification of Haemophilus species is a challenge in clinical practice. In this study, we characterized the phenotypic and genotypic features of four H. seminalis strains that were isolated from human sputum specimens and propose the "H. intermedius" and hemin (X-factor)-independent H. haemolyticus isolates as belonging to H. seminalis. The prediction of virulence-related genes indicates that H. seminalis isolates carry several virulence genes that are likely to play an important role in its pathogenicity. In addition, we depict that the genes ispD, pepG, and moeA can be used as biomarkers for distinguishing H. seminalis from H. haemolyticus and H. influenzae. Our findings provide some insights into the identification, epidemiology, genetic diversity, pathogenic potential, and antimicrobial resistance of the newly proposed H. seminalis.


Assuntos
Haemophilus , Hemina , Humanos , RNA Ribossômico 16S/genética , Haemophilus/genética , Haemophilus influenzae , Genômica , Filogenia , Variação Genética
10.
Sci Rep ; 13(1): 5715, 2023 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-37029178

RESUMO

Increasing evidence indicates that respiratory tract microecological disorders may play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Understanding the composition of the respiratory microbiome in COPD and its relevance to respiratory immunity will help develop microbiome-based diagnostic and therapeutic approaches. One hundred longitudinal sputum samples from 35 subjects with acute exacerbation of COPD (AECOPD) were analysed for respiratory bacterial microbiome using 16S ribosomal RNA amplicon sequencing technology, and the sputum supernatant was analysed for 12 cytokines using a Luminex liquid suspension chip. Unsupervised hierarchical clustering was employed to evaluate the existence of distinct microbial clusters. In AECOPD, the respiratory microbial diversity decreased, and the community composition changed significantly. The abundances of Haemophilus, Moraxella, Klebsiella, and Pseudomonas increased significantly. Significant positive correlations between the abundance of Pseudomonas and TNF-α, abundance of Klebsiella and the percentage of eosinophils were observed. Furthermore, COPD can be divided into four clusters based on the respiratory microbiome. AECOPD-related cluster was characterized by the enrichment of Pseudomonas and Haemophilus and a high level of TNF-α. Lactobacillus and Veillonella are enriched in therapy-related phenotypes and may play potential probiotic roles. There are two inflammatory endotypes in the stable state: Gemella is associated with the Th2 inflammatory endotypes, whereas Prevotella is associated with the Th17 inflammatory endotypes. Nevertheless, no differences in clinical manifestations were found between these two endotypes. The sputum microbiome is associated with the disease status of COPD, allowing us to distinguish different inflammatory endotypes. Targeted anti-inflammatory and anti-infective therapies may improve the long-term prognosis of COPD.


Assuntos
Microbiota , Doença Pulmonar Obstrutiva Crônica , Humanos , Estudos de Coortes , Fator de Necrose Tumoral alfa , Doença Pulmonar Obstrutiva Crônica/patologia , Pulmão/patologia , Haemophilus , Escarro/microbiologia , Progressão da Doença
11.
Microbiome ; 11(1): 29, 2023 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-36803868

RESUMO

BACKGROUND: Long-term azithromycin (AZM) treatment reduces the frequency of acute respiratory exacerbation in children and adolescents with HIV-associated chronic lung disease (HCLD). However, the impact of this treatment on the respiratory bacteriome is unknown. METHOD: African children with HCLD (defined as forced expiratory volume in 1 s z-score (FEV1z) less than - 1.0 with no reversibility) were enrolled in a placebo-controlled trial of once-weekly AZM given for 48-weeks (BREATHE trial). Sputum samples were collected at baseline, 48 weeks (end of treatment) and 72 weeks (6 months post-intervention in participants who reached this timepoint before trial conclusion). Sputum bacterial load and bacteriome profiles were determined using 16S rRNA gene qPCR and V4 region amplicon sequencing, respectively. The primary outcomes were within-participant and within-arm (AZM vs placebo) changes in the sputum bacteriome measured across baseline, 48 weeks and 72 weeks. Associations between clinical or socio-demographic factors and bacteriome profiles were also assessed using linear regression. RESULTS: In total, 347 participants (median age: 15.3 years, interquartile range [12.7-17.7]) were enrolled and randomised to AZM (173) or placebo (174). After 48 weeks, participants in the AZM arm had reduced sputum bacterial load vs placebo arm (16S rRNA copies/µl in log10, mean difference and 95% confidence interval [CI] of AZM vs placebo - 0.54 [- 0.71; - 0.36]). Shannon alpha diversity remained stable in the AZM arm but declined in the placebo arm between baseline and 48 weeks (3.03 vs. 2.80, p = 0.04, Wilcoxon paired test). Bacterial community structure changed in the AZM arm at 48 weeks compared with baseline (PERMANOVA test p = 0.003) but resolved at 72 weeks. The relative abundances of genera previously associated with HCLD decreased in the AZM arm at 48 weeks compared with baseline, including Haemophilus (17.9% vs. 25.8%, p < 0.05, ANCOM ω = 32) and Moraxella (1% vs. 1.9%, p < 0.05, ANCOM ω = 47). This reduction was sustained at 72 weeks relative to baseline. Lung function (FEV1z) was negatively associated with bacterial load (coefficient, [CI]: - 0.09 [- 0.16; - 0.02]) and positively associated with Shannon diversity (0.19 [0.12; 0.27]). The relative abundance of Neisseria (coefficient, [standard error]: (2.85, [0.7], q = 0.01), and Haemophilus (- 6.1, [1.2], q < 0.001) were positively and negatively associated with FEV1z, respectively. An increase in the relative abundance of Streptococcus from baseline to 48 weeks was associated with improvement in FEV1z (3.2 [1.11], q = 0.01) whilst an increase in Moraxella was associated with decline in FEV1z (-2.74 [0.74], q = 0.002). CONCLUSIONS: AZM treatment preserved sputum bacterial diversity and reduced the relative abundances of the HCLD-associated genera Haemophilus and Moraxella. These bacteriological effects were associated with improvement in lung function and may account for reduced respiratory exacerbations associated with AZM treatment of children with HCLD. Video Abstract.


Assuntos
Infecções por HIV , Pneumopatias , Adolescente , Humanos , Criança , Azitromicina/uso terapêutico , Antibacterianos/uso terapêutico , Escarro/microbiologia , Carga Bacteriana , RNA Ribossômico 16S/genética , Pneumopatias/tratamento farmacológico , Bactérias/genética , Haemophilus , Moraxella , Pulmão/microbiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico
12.
Microbiol Spectr ; 11(1): e0386022, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36475849

RESUMO

Patients with chronic obstructive pulmonary disease (COPD) benefit from the immunomodulatory effect of azithromycin, but long-term administration may alter colonizing bacteria. Our goal was to identify changes in Haemophilus influenzae and Haemophilus parainfluenzae during azithromycin treatment. Fifteen patients were followed while receiving prolonged azithromycin treatment (Hospital Universitari de Bellvitge, Spain). Four patients (P02, P08, P11, and P13) were persistently colonized by H. influenzae for at least 3 months and two (P04 and P11) by H. parainfluenzae. Isolates from these patients (53 H. influenzae and 18 H. parainfluenzae) were included to identify, by whole-genome sequencing, antimicrobial resistance changes and genetic variation accumulated during persistent colonization. All persistent lineages isolated before treatment were azithromycin-susceptible but developed resistance within the first months, apart from those belonging to P02, who discontinued the treatment. H. influenzae isolates from P08-ST107 acquired mutations in 23S rRNA, and those from P11-ST2480 and P13-ST165 had changes in L4 and L22. In H. parainfluenzae, P04 persistent isolates acquired changes in rlmC, and P11 carried genes encoding MefE/MsrD efflux pumps in an integrative conjugative element, which was also identified in H. influenzae P11-ST147. Other genetic variation occurred in genes associated with cell wall and inorganic ion metabolism. Persistent H. influenzae strains all showed changes in licA and hgpB genes. Other genes (lex1, lic3A, hgpC, and fadL) had variation in multiple lineages. Furthermore, persistent strains showed loss, acquisition, or genetic changes in prophage-associated regions. Long-term azithromycin therapy results in macrolide resistance, as well as genetic changes that likely favor bacterial adaptation during persistent respiratory colonization. IMPORTANCE The immunomodulatory properties of azithromycin reduce the frequency of exacerbations and improve the quality of life of COPD patients. However, long-term administration may alter the respiratory microbiota, such as Haemophilus influenzae, an opportunistic respiratory colonizing bacteria that play an important role in exacerbations. This study contributes to a better understanding of COPD progression by characterizing the clinical evolution of H. influenzae in a cohort of patients with prolonged azithromycin treatment. The emergence of macrolide resistance during the first months, combined with the role of Haemophilus parainfluenzae as a reservoir and source of resistance dissemination, is a cause for concern that may lead to therapeutic failure. Furthermore, genetic variations in cell wall and inorganic ion metabolism coding genes likely favor bacterial adaptation to host selective pressures. Therefore, the bacterial pathoadaptive evolution in these severe COPD patients raise our awareness of the possible spread of macrolide resistance and selection of host-adapted clones.


Assuntos
Infecções por Haemophilus , Doença Pulmonar Obstrutiva Crônica , Humanos , Azitromicina/uso terapêutico , Azitromicina/farmacologia , Haemophilus/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Qualidade de Vida , Infecções por Haemophilus/tratamento farmacológico , Infecções por Haemophilus/microbiologia , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Farmacorresistência Bacteriana/genética , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/microbiologia , Sistema Respiratório , Haemophilus influenzae
13.
J Cardiothorac Surg ; 17(1): 185, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35986339

RESUMO

Infective endocarditis (IE) is a severe disease that is still associated with high mortality despite recent advances in diagnosis and treatment. HACEK organisms (Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae) are gram-negative bacteria that are part of the normal flora of the mouth and upper respiratory tract in humans. These organisms cause a wide range of infections, of which IE is one of the most notable. In order to control and prevent endocarditis caused by HACEK, measures such as oral hygiene and the use of prophylactic drugs should be used for people at risk, including people with underlying heart disease and people with artificial valves. This review is a summary of the main aspects of IE focusing on HACEK organisms.


Assuntos
Endocardite Bacteriana , Endocardite , Cardiopatias , Eikenella corrodens , Endocardite/diagnóstico , Endocardite/terapia , Endocardite Bacteriana/microbiologia , Haemophilus , Humanos
14.
Infect Dis Now ; 52(4): 227-229, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35483632

RESUMO

BACKGROUND: We report for the first time the association of Haemophilus pittmaniae and Haemophilus sputorum with urethritis in men who have sex with men and who engage in unprotected intercourse. PATIENTS AND METHODS: A search for genital pathogens was conducted using urethral exudate cultures and PCR tests for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma spp., and Ureaplasma spp. Recovered microorganisms were identified by MALDI-TOF mass spectrometry, and their susceptibility was evaluated by diffusion gradient test. RESULTS: H. pittmaniae and H. sputorum were isolated. They both proved susceptible to ampicillin, cefixime, and trimethoprim/sulfamethoxazole. H. pittmaniae was also susceptible to tetracycline and H. sputorum to moxifloxacin. CONCLUSION: The increased frequency of potentially resistant Haemophilus spp. isolates in genital exudates highlights the need for greater surveillance of these microorganisms and for their consideration in the differential diagnosis of genital system infections.


Assuntos
Minorias Sexuais e de Gênero , Infecções Urinárias , Genitália , Haemophilus , Homossexualidade Masculina , Humanos , Masculino
15.
Lett Appl Microbiol ; 75(1): 17-23, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35285055

RESUMO

This study aimed to evaluate the filter paper as a means to transport inactivated Gram-negative non-fermentative (GNNF) bacteria and Haemophilus spp. for analysis using MALDI-TOF MS. A total of 133 isolates were evaluated and the analysis of each isolate was performed directly from original bacterial colony and in filter paper after the processing. To evaluate the agreement between the identification performed directly from the colony and after impregnation in filter paper, we assign the scores: >2·3 as excellent (E); 2·0 to 2·3 as very good (VG); 1·7-1·99 as good (G); <1·7 as unidentified (U). The divergences were classified as: Minor Divergence, Intermediate Divergence and Major Divergence. A total of 80 isolates transported in the filter paper disks presented full category concordance; 39 isolates presented Minor Divergence; 4 isolates present Intermediate Divergence; 4 isolates present Major Divergence and 6 isolates present better results after impregnation in filter paper. The proposed methodology of bacteria transportation presented a sensitivity of 96·9% and a specificity of 100%. The filter paper as a means to transport and storage of inactivated GNNF and Haemophilus spp. may be considered a potential tool for faster, more accurate, biosafe and less-expensive identification.


Assuntos
Bactérias Gram-Negativas , Haemophilus , Bactérias , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
16.
Genome Med ; 14(1): 13, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-35139905

RESUMO

BACKGROUND: Bacteria belonging to the genus Haemophilus cause a wide range of diseases in humans. Recently, H. influenzae was classified by the WHO as priority pathogen due to the wide spread of ampicillin resistant strains. However, other Haemophilus spp. are often misclassified as H. influenzae. Therefore, we established an accurate and rapid whole genome sequencing (WGS) based classification and serotyping algorithm and combined it with the detection of resistance genes. METHODS: A gene presence/absence-based classification algorithm was developed, which employs the open-source gene-detection tool SRST2 and a new classification database comprising 36 genes, including capsule loci for serotyping. These genes were identified using a comparative genome analysis of 215 strains belonging to ten human-related Haemophilus (sub)species (training dataset). The algorithm was evaluated on 1329 public short read datasets (evaluation dataset) and used to reclassify 262 clinical Haemophilus spp. isolates from 250 patients (German cohort). In addition, the presence of antibiotic resistance genes within the German dataset was evaluated with SRST2 and correlated with results of traditional phenotyping assays. RESULTS: The newly developed algorithm can differentiate between clinically relevant Haemophilus species including, but not limited to, H. influenzae, H. haemolyticus, and H. parainfluenzae. It can also identify putative haemin-independent H. haemolyticus strains and determine the serotype of typeable Haemophilus strains. The algorithm performed excellently in the evaluation dataset (99.6% concordance with reported species classification and 99.5% with reported serotype) and revealed several misclassifications. Additionally, 83 out of 262 (31.7%) suspected H. influenzae strains from the German cohort were in fact H. haemolyticus strains, some of which associated with mouth abscesses and lower respiratory tract infections. Resistance genes were detected in 16 out of 262 datasets from the German cohort. Prediction of ampicillin resistance, associated with blaTEM-1D, and tetracycline resistance, associated with tetB, correlated well with available phenotypic data. CONCLUSIONS: Our new classification database and algorithm have the potential to improve diagnosis and surveillance of Haemophilus spp. and can easily be coupled with other public genotyping and antimicrobial resistance databases. Our data also point towards a possible pathogenic role of H. haemolyticus strains, which needs to be further investigated.


Assuntos
Antibacterianos , Infecções por Haemophilus , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Haemophilus/genética , Infecções por Haemophilus/epidemiologia , Infecções por Haemophilus/microbiologia , Humanos , Sequenciamento Completo do Genoma
17.
Nat Microbiol ; 7(2): 224-237, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35058634

RESUMO

The respiratory tract is populated by a specialized microbial ecosystem, which is seeded during and directly following birth. Perturbed development of the respiratory microbial community in early-life has been associated with higher susceptibility to respiratory tract infections (RTIs). Given a consistent gap in time between first signs of aberrant microbial maturation and the observation of the first RTIs, we hypothesized that early-life host-microbe cross-talk plays a role in this process. We therefore investigated viral presence, gene expression profiles and nasopharyngeal microbiota from birth until 12 months of age in 114 healthy infants. We show that the strongest dynamics in gene expression profiles occurred within the first days of life, mostly involving Toll-like receptor (TLR) and inflammasome signalling. These gene expression dynamics coincided with rapid microbial niche differentiation. Early asymptomatic viral infection co-occurred with stronger interferon activity, which was related to specific microbiota dynamics following, including early enrichment of Moraxella and Haemophilus spp. These microbial trajectories were in turn related to a higher number of subsequent (viral) RTIs over the first year of life. Using a multi-omic approach, we found evidence for species-specific host-microbe interactions related to consecutive susceptibility to RTIs. Although further work will be needed to confirm causality of our findings, together these data indicate that early-life viral encounters could impact subsequent host-microbe cross-talk, which is linked to later-life infections.


Assuntos
Interações entre Hospedeiro e Microrganismos , Microbiota/genética , Infecções Respiratórias/imunologia , Infecções Respiratórias/virologia , Viroses/imunologia , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Haemophilus/imunologia , Humanos , Lactente , Recém-Nascido , Inflamassomos , Masculino , Microbiota/imunologia , Moraxella/imunologia , Nasofaringe/virologia , Recidiva , Infecções Respiratórias/fisiopatologia , Especificidade da Espécie
18.
J Microbiol Methods ; 193: 106417, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35033634

RESUMO

Many factors affecting satellitism tests are unclear, and it is difficult to avoid misidentification, even if the medium is properly selected. We investigated the factors causing false-positive results for Haemophilus influenzae and false-negative results for Haemophilus parainfluenzae in the satellitism tests using Staphylococcus aureus as the source of nicotinamide adenine dinucleotide (NAD). H. influenzae (four reference strains and 47 clinical isolates), H. parainfluenzae (two reference strains and 67 clinical isolates), four different media, and two strains of S. aureus revived on two different media were used in this study. The type of medium used to revive S. aureus was the most common factor causing false-positive results for H. influenzae, followed by different strains of S. aureus and the type of medium used for the experiment. The production of false-negative results for H. parainfluenzae was only related to the medium used in the experiment. To improve the accuracy of the tests in routine laboratories, using S. aureus as the source of NAD, tryptic soy agar, and S. aureus (ATCC 25923) revived on nutrient agar should be adopted.


Assuntos
Infecções por Haemophilus , Haemophilus influenzae , Ágar , Meios de Cultura , Haemophilus , Haemophilus parainfluenzae , Humanos , Indicadores e Reagentes , NAD , Staphylococcus aureus
19.
Can J Cardiol ; 38(1): 126-128, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34619338

RESUMO

Coronary artery embolization is an unusual complication following infective endocarditis (IE) surgery. A 43-year-old woman developed an anterior ST-elevation myocardial infarction (STEMI) with acute left anterior descending artery occlusion due to septic emboli during the immediate postoperative period following minimally invasive mitral valve repair for IE. It was successfully treated with thromboaspiration and balloon angioplasty. Coronary septic emboli should be part of the differential diagnosis in patients presenting with STEMI during the early postoperative period for IE.


Assuntos
Oclusão Coronária/cirurgia , Endocardite/complicações , Infecções por Haemophilus/complicações , Valva Mitral/cirurgia , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Sepse/complicações , Adulto , Angiografia Coronária , Oclusão Coronária/complicações , Oclusão Coronária/diagnóstico , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Endocardite/diagnóstico , Endocardite/microbiologia , Feminino , Haemophilus/isolamento & purificação , Infecções por Haemophilus/diagnóstico , Infecções por Haemophilus/microbiologia , Doenças das Valvas Cardíacas/cirurgia , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Sepse/microbiologia
20.
Emerg Infect Dis ; 28(1): 104-110, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34932443

RESUMO

The prevalence of antimicrobial resistance among Haemophilus spp. is a critical concern, but high-level quinolone-resistant strains had not been isolated from children. We isolated high-level quinolone-resistant H. haemolyticus from the suction sputum of a 9-year-old patient. The patient had received home medical care with mechanical ventilation for 2 years and had not been exposed to any quinolones for >3 years. The H. haemolyticus strain we isolated, 2019-19, shared biochemical features with H. influenzae. However, whole-genome analysis found this strain was closer to H. haemolyticus. Phylogenetic and mass spectrometry analyses indicated that strain 2019-19 was in the same cluster as H. haemolyticus. Comparison of quinolone resistance-determining regions showed strain 2019-19 possessed various amino acid substitutions, including those associated with quinolone resistance. This report highlights the existence of high-level quinolone-resistant Haemophilus species that have been isolated from both adults and children.


Assuntos
Infecções por Haemophilus , Quinolonas , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Criança , Haemophilus/genética , Infecções por Haemophilus/tratamento farmacológico , Haemophilus influenzae , Humanos , Filogenia , Quinolonas/farmacologia
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