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1.
Infect Immun ; 87(11)2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31481409

RESUMO

Neutrophils contribute to lung injury in acute pneumococcal pneumonia. The interleukin 17 receptor E (IL-17RE) is the functional receptor for the epithelial-derived cytokine IL-17C, which is known to mediate innate immune functions. The aim of this study was to investigate the contribution of IL-17RE/IL-17C to pulmonary inflammation in a mouse model of acute Streptococcus pneumoniae pneumonia. Numbers of neutrophils and the expression levels of the cytokine granulocyte colony-stimulating factor (G-CSF) and tumor necrosis factor alpha (TNF-α) were decreased in lungs of IL-17RE-deficient (Il-17re-/- ) mice infected with S. pneumoniae Numbers of alveolar macrophages rapidly declined in both wild-type (WT) and Il-17re-/- mice and recovered 72 h after infection. There were no clear differences in the elimination of bacteria and numbers of blood granulocytes between infected WT and Il-17re-/- mice. The fractions of granulocyte-monocyte progenitors (GMPs) were significantly reduced in infected Il-17re-/- mice. Numbers of neutrophils were significantly reduced in lungs of mice deficient for IL-17C 24 h after infection with S. pneumoniae These data indicate that the IL-17C/IL-17RE axis promotes the recruitment of neutrophils without affecting the recovery of alveolar macrophages in the acute phase of S. pneumoniae lung infection.


Assuntos
Interleucina-17/metabolismo , Neutrófilos/fisiologia , Pneumonia Pneumocócica/metabolismo , Receptores de Interleucina-17/metabolismo , Animais , Diferenciação Celular , Feminino , Granulócitos , Interleucina-17/genética , Camundongos , Camundongos Knockout , Pneumonia Pneumocócica/microbiologia , Receptores de Interleucina-17/genética , Streptococcus pneumoniae
2.
Infect Immun ; 87(11)2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31451619

RESUMO

Streptococcus pneumoniae (pneumococcus) causes multiple infectious diseases. The pneumococcal competence system facilitates genetic transformation, spreads antibiotic resistance, and contributes to virulence. DNA-processing protein A (DprA) regulates the exit of pneumococcus from the competent state. Previously, we have shown that DprA is important in both bacteremia and pneumonia infections. Here, we examined the mechanisms of virulence attenuation in a ΔdprA mutant. Compared to the parental wild-type D39, the ΔdprA mutant enters the competent state when exposed to lower concentrations of the competence-stimulating peptide CSP1. The ΔdprA mutant overexpresses ComM, which delays cell separation after division. Additionally, the ΔdprA mutant overexpresses allolytic factors LytA, CbpD, and CibAB and is more susceptible to detergent-triggered lysis. Disabling of the competent-state-specific induction of ComM and allolytic factors compensated for the virulence loss in the ΔdprA mutant, suggesting that overexpression of these factors contributes to virulence attenuation. Finally, the ΔdprA mutant fails to downregulate the expression of multiple competence-regulated genes, leading to the excessive energy consumption. Collectively, these results indicate that an inability to properly exit the competent state disrupts multiple cellular processes that cause virulence attenuation in the ΔdprA mutant.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Membrana/metabolismo , Streptococcus pneumoniae/genética , Animais , Proteínas de Bactérias/genética , Feminino , Deleção de Genes , Regulação Bacteriana da Expressão Gênica , Masculino , Proteínas de Membrana/genética , Camundongos , Nasofaringe/microbiologia , Pneumonia Pneumocócica/microbiologia
3.
Int J Infect Dis ; 85: 1-6, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31096052

RESUMO

OBJECTIVES: The aim of this study was to estimate the impact of antimicrobial resistance (AMR) in secondary pneumococcal pneumonia infections on global mortality during the 2009 influenza pandemic, to estimate future pandemic mortality risk and to inform pandemic preparedness. METHODS: Risk analysis modelling was conducted using a multivariate risk formula. Literature reviews were conducted to generate global central estimates for each of the parameters of the risk formula in relation to the 2009 influenza pandemic, secondary pneumococcal pneumonia, rates of AMR, and pneumococcal vaccine efficacy as a component of pandemic preparedness. RESULTS: Global Streptococcus pneumoniae AMR was estimated at 21.8% to 27.6%, and contributed to 1.8% to 2.3% of deaths during the 2009 influenza pandemic. When directly applied to mortality due to multidrug resistance, pneumococcal vaccination could potentially prevent 1277 to 3754 deaths and could have reduced mortality from multidrug-resistant S. pneumoniae to 1% to 1.2%. CONCLUSIONS: AMR in secondary pneumococcal infections contributed towards a small percentage of the global mortality during the 2009 influenza pandemic. Increased S. pneumoniae AMR could result in a three- to four-fold rise in mortality due to secondary pneumococcal infections in future influenza pandemics. Pneumococcal vaccination has an important role in preventing pneumococcal co-infections and combating AMR in all populations, and should be considered a key component of influenza pandemic preparedness or early action plans.


Assuntos
Antibacterianos/farmacologia , Coinfecção/mortalidade , Farmacorresistência Bacteriana , Influenza Humana/complicações , Pneumonia Pneumocócica/mortalidade , Streptococcus pneumoniae/efeitos dos fármacos , Adolescente , Adulto , Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , Coinfecção/microbiologia , Feminino , Humanos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/genética , Vacinas Pneumocócicas/imunologia , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/etiologia , Pneumonia Pneumocócica/microbiologia , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/fisiologia , Vacinação , Adulto Jovem
4.
J Med Case Rep ; 13(1): 126, 2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31029142

RESUMO

INTRODUCTION: Primary peritonitis without an identifiable intra-abdominal source is extremely rare in healthy individuals; it is commonly seen in cases of nephrotic syndrome, cirrhosis and end-stage liver disease, ascites, immunosuppression, and inflamed peritoneum due to pre-existing autoimmune and oncological conditions. CASE PRESENTATION: We present the case of a 68-year-old Caucasian woman operated on due to acute abdomen with a provisional diagnosis of acute appendicitis. During the operation a small amount of free intra-abdominal fluid was found. Her uterus, ovaries, and fallopian tubes were macroscopically normal. Therefore, with the suspicion of appendicitis, appendectomy was performed. Her blood cultures were negative while peritoneal fluid was positive for capsulated form of Streptococcus pneumoniae. A 30-day follow-up was performed and she was asymptomatic without any sign of infection. DISCUSSION: Streptococcus pneumoniae commonly causes upper respiratory tract infection and cutaneous infections. It very rarely causes gastrointestinal infection and it is very rarely responsible for primary peritonitis and septic shock syndrome. CONCLUSION: Pneumococcal peritonitis has a rare occurrence and represents a clinical challenge because of its subtle and non-specific clinical findings. The interest in our case lays in the relatively rare diagnosis of primary peritonitis mimicking acute appendicitis.


Assuntos
Peritonite/etiologia , Pneumonia Pneumocócica/complicações , Abdome Agudo/etiologia , Idoso , Apendicite/diagnóstico , Diagnóstico Diferencial , Humanos , Imunocompetência , Peritonite/diagnóstico , Pneumonia Pneumocócica/microbiologia , Streptococcus pneumoniae/isolamento & purificação
5.
Eur J Clin Microbiol Infect Dis ; 38(7): 1249-1254, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30949897

RESUMO

Culture of expectorated sputum in the microbiological diagnosis of community-acquired pneumonia (CAP) is considered valid only if high-quality (HQ) samples are obtained, but evidence regarding pneumococcal etiology specifically is lacking. We studied 323 radiologically confirmed CAP cases in patients aged ≥ 65 years. Sputum samples were assessed for quality microscopically and cultured. Two quality criteria sets were applied to delineate HQ from low-quality (LQ) sputa: leukocytes/epithelial cells ratio > 5 and ≤ 2.5 epithelial cells/400× magnification field (HQ1), or leukocytes/epithelial cells ratio > 1 (HQ2). A sputum sample was obtained and the quality assessed in 224 cases; 47% were HQ1 and 76% HQ2. Encapsulated pneumococci (EPnc) were cultured in 25 (24%), 14 (12%), 35 (21%), and 4 (7%) of the HQ1-, LQ1-, HQ2-, and LQ2-samples, respectively. If another pneumococcal test (blood culture, urine antigen, or ≥ twofold increase in CbpA or PsaA antibodies) was positive, EPnc were cultured at similar proportions in HQ1- and LQ1-sputa; if the other test was negative, EPnc were cultured less often in LQ1- than HQ1-sputa. EPnc were found less often in LQ2- than in HQ2-sputa. Our results suggest similar specificity in LQ- and HQ-sputum cultures. All sputum samples add value to the pneumococcal CAP-diagnosis in the elderly.


Assuntos
Infecções Comunitárias Adquiridas/diagnóstico , Pneumonia Pneumocócica/diagnóstico , Escarro/microbiologia , Streptococcus pneumoniae/isolamento & purificação , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Contagem de Colônia Microbiana , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Humanos , Masculino , Pneumonia Pneumocócica/microbiologia , Sensibilidade e Especificidade , Sorotipagem , Streptococcus pneumoniae/crescimento & desenvolvimento
6.
Microb Pathog ; 130: 271-282, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30914386

RESUMO

Streptococcus pneumoniae is widely recognized as the main cause of bacterial pneumonia among all age groups. Other important gram-positive, gram-negative and atypical bacteria causing pneumonia majorly infect children and infants. Despite abundant occurrence of bacterial pneumonia, there is no specific antibiotic therapy available. On the other hand non-specific therapies are less effective and may influence bacterial resistance. Therefore, search for novel drug targets for pathogen is highly necessary. The current study suggested novel potential drug targets through the subtractive and comparative genomics approach. Putative drug targets were identified from highly virulent strain of Streptococcus pneumoniae using target identification (TiD) software and compared with other 12 pneumonia causing pathogens. The putative targets were prioritized through druggability analysis, virulence analysis, metabolic pathway enrichment followed by functional annotations and interactome network. Prioritization of 74 drug targets revealed that 42 of them were enzymes which included 29 new targets and seven chokepoint enzymes. Twenty (out of 74) potential targets are proposed as hub genes through interactome analysis and explored their significance in survival of the pathogen. Comparative analysis of 20 hub genes represents that 15 are enzymes and five are non-enzymes. Functional annotation of two chokepoint hub enzymes namely, peptidoglycan bridge formation alanyltransferase MurN (fibB) and PTS mannitol transporter subunit IIA (mltF) were significantly enriched in peptidoglycan biosynthesis and phosphotransferase system (PTS) respectively. Therefore these enzymes would be of prior interest for rational design of targeted therapy against bacterial pneumonia.


Assuntos
Antibacterianos/farmacologia , Biologia Computacional , Pneumonia Pneumocócica/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos , Genômica , Humanos , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Streptococcus pneumoniae/genética
7.
Microb Drug Resist ; 25(5): 744-751, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30676875

RESUMO

Pneumococcal isolates from adult patients in northern Japan in 2016 were subjected to molecular investigation related to pneumococcal surface protein A (PspA) and drug resistance determinants. Of the 51 isolates, serotype 3/ST180 was the most prevalent (17.6%), followed by 35B (ST2755/ST558) (11.8%) and 15A (ST63/ST7874/ST13068/ST13785) (9.8%). Coverage of serotypes by 13-valent conjugate vaccine and 23-valent polysaccharide vaccine was 27.5% and 49%, respectively. All the isolates expressed PspA family 1 or 2 (51% and 49%, respectively). Each serotype was associated with either of the PspA families (e.g., serotype 3, PspA family 1; serotypes 35B and 15A, PspA family 2). Multidrug resistance (MDR) was found in 84.3% of the isolates. Minimum of one altered penicillin-binding protein gene was detected in 82.4% of isolates, indicating 25.5% non-susceptibility to penicillin. Serotypes 15A and 35B were predominant and demonstrated MDR. An isolate of serotype 15A/ST13785 (single-locus variant of ST242) was resistant to fluoroquinolones associated with double mutation in the quinolone resistance-determining regions of gyrA and parC. The present study indicates the spread of MDR pneumococci represented by isolates of serotypes 3, 15A, and 35B, and prevalence of both PspA family 1 and 2 in isolates obtained from adult patients.


Assuntos
Proteínas de Bactérias/genética , Farmacorresistência Bacteriana Múltipla/genética , Proteínas de Ligação às Penicilinas/genética , Pneumonia Pneumocócica/epidemiologia , Streptococcus pneumoniae/genética , Adolescente , Adulto , Antibacterianos/farmacologia , DNA Girase/genética , DNA Topoisomerase IV/genética , Feminino , Fluoroquinolonas/farmacologia , Expressão Gênica , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Mutação , Vacinas Pneumocócicas/administração & dosagem , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/microbiologia , Pneumonia Pneumocócica/prevenção & controle , Prevalência , Sorogrupo , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação
8.
Expert Rev Anti Infect Ther ; 17(2): 107-115, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30618315

RESUMO

INTRODUCTION: Community-acquired pneumonia (CAP) continues to be a leading cause of hospitalization and mortality worldwide. Streptococcus pneumoniae and Legionella pneumophila remain the major etiological agents and are responsible for a significant proportion of CAP mortality. Among diagnostic tests for CAP, urine antigen detection of S. pneumoniae and L. pneumophila is widely accepted due to the simplicity of collection and the rapidity of the test results. Areas covered: This comprehensive review outlines the urinary antigen tests available, discusses their sensitivity and specificity, and assesses the usefulness of their results as the basis for targeted therapy. Expert commentary: There have been advances in urine antigen detection tests for patients with CAP. New methodologies show greater sensitivity, detect S. pneumoniae and L. pneumophila in a single test, and also detect pneumococcal serotypes. In addition, urine antigen detection tests have shown a high specificity, which means that a positive result practically indicates the causative pathogen of CAP. Therefore, a positive result can lead to a targeted therapy that is likely to improve patient outcomes and reduce the risk of resistance and adverse events. However, well-designed studies are needed to evaluate the usefulness of urine antigen detection tests with regard to clinical outcomes.


Assuntos
Antígenos de Bactérias/urina , Infecções Comunitárias Adquiridas/diagnóstico , Pneumonia Bacteriana/diagnóstico , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Infecções Comunitárias Adquiridas/microbiologia , Farmacorresistência Bacteriana , Hospitalização , Humanos , Legionella pneumophila/isolamento & purificação , Doença dos Legionários/diagnóstico , Doença dos Legionários/microbiologia , Pneumonia Bacteriana/microbiologia , Pneumonia Pneumocócica/diagnóstico , Pneumonia Pneumocócica/microbiologia , Sensibilidade e Especificidade , Streptococcus pneumoniae/isolamento & purificação
9.
Chest ; 155(4): 795-804, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30471269

RESUMO

BACKGROUND: Antibiotic combinations that include macrolides have shown lower mortality rates than ß-lactams in monotherapy or combined with fluoroquinolones in patients with community-acquired pneumonia (CAP). However, this effect has not been studied according to the levels of C-reactive protein in CAP with identified microbial cause. In patients with CAP and known microbial cause we aimed to evaluate 30-day mortality of a ß-lactam plus macrolide (BL + M) compared with a fluoroquinolone alone or with a ß-lactam (FQ ± BL). METHODS: We analyzed a prospective observational cohort of patients with CAP admitted to the Hospital Clinic of Barcelona between 1996 and 2016. We included only patients with known microbial cause. RESULTS: Of 1,715 patients (29%) with known etiology, a total of 932 patients (54%) received BL + M. Despite lower crude mortality in the BL + M group in the overall population (BL + M, 5% vs FQ ± BL, 8%; P = .015), after adjustment by a propensity score and baseline characteristics, the combination of BL + M had a protective effect on mortality only in patients with high inflammatory response (C-reactive protein, > 15 mg/dL) and pneumococcal CAP (adjusted OR, 0.28; 95% CI, 0.09-0.93). No benefits on mortality were observed for the population without high inflammatory response and pneumococcal CAP or with other etiologies. CONCLUSIONS: The combination of a ß-lactam with a macrolide was associated with decreased mortality in patients with pneumococcal CAP and in patients with high systemic inflammatory response. When both factors occurred together, BL + M was protective for mortality in the multivariate analysis.


Assuntos
Infecções Comunitárias Adquiridas/tratamento farmacológico , Macrolídeos/uso terapêutico , Pneumonia Pneumocócica/tratamento farmacológico , Pontuação de Propensão , Streptococcus pneumoniae/isolamento & purificação , beta-Lactamas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Causas de Morte/tendências , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/mortalidade , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pneumonia Pneumocócica/microbiologia , Pneumonia Pneumocócica/mortalidade , Estudos Prospectivos , Espanha/epidemiologia , Escarro/microbiologia , Taxa de Sobrevida/tendências
10.
J Infect Dis ; 219(10): 1545-1553, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30561674

RESUMO

BACKGROUND: The pathogenicity of Streptococcus pneumoniae under anaerobic conditions remains largely unknown. We examined the pathogenicity of S. pneumoniae cultured under anaerobic conditions in a murine model of pneumococcal pneumonia. METHODS: Mice were infected with S. pneumoniae grown under anaerobic or aerobic conditions. The pathogenic effects in vivo in the lower airway tract were then compared. The effect of anaerobic culture on lytA/ply transcript levels in vitro and in vivo were analyzed by quantitative real-time polymerase chain reaction. RESULTS: Mice inoculated with anaerobically cultured S. pneumoniae exhibited significantly lower survival rates and higher bacterial loads in the lungs and blood as compared to those infected with aerobically cultured S. pneumoniae. Aerobically cultured S. pneumoniae in the early log phase of growth was also able to induce severe pneumonia at levels equivalent to those of anaerobic S. pneumoniae. However, ply/gyrB transcript levels were significantly increased in the lungs of mice infected with anaerobically grown S. pneumoniae. In vitro, S. pneumoniae grown under anaerobic culture conditions demonstrated greater proliferation than S. pneumoniae grown under aerobic culture conditions, and bacterial concentrations were maintained for 24 hours without detectable upregulation of lytA messenger RNA. CONCLUSIONS: S. pneumoniae grown under anaerobic conditions had the potential to induce severe invasive bacteremic pneumococcal pneumonia in a manner different from that of S. pneumoniae grown under aerobic conditions.


Assuntos
Pneumonia Pneumocócica/microbiologia , Streptococcus pneumoniae/patogenicidade , Fatores de Virulência/genética , Anaerobiose , Animais , Proteínas de Bactérias/genética , Técnicas Bacteriológicas , Genes Bacterianos , Pulmão/microbiologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos BALB C , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/metabolismo , Estreptolisinas/genética , Estreptolisinas/metabolismo , Fatores de Virulência/metabolismo
11.
Mol Biol Rep ; 46(1): 1013-1021, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30569391

RESUMO

Streptococcus pneumoniae is the most important pathogen causing community-acquired pneumonia (CAP). The current diagnostic microbial standard detects S. pneumoniae in less than 30% of CAP cases. A quantitative polymerase chain reaction (PCR) targeting autolysin (lytA) is able to increase the rate of detection. The aim of this study is validation of this quantitative PCR in vitro using different available strains and in vivo using clinical samples (oropharyngeal swabs). The PCR autolysin (lytA) was validated by testing the intra- and inter-run variability. Also, the in vitro specificity and sensitivity, including the lower limit of detection was determined. In addition, a pilot-study was performed using samples from patients (n = 28) with pneumococcal pneumonia and patients (n = 28) with a pneumonia without detection of S. pneumoniae with the current diagnostic microbial standard, but with detection of either a viral and or another bacterial pathogen to validate this test further. The intra- and inter-run variability were relatively low (SD's ranging from 0.08 to 0.96 cycle thresholds). The lower limit of detection turned out to be 1-10 DNA copies/reaction. In-vitro sensitivity and specificity of the tested specimens (8 strains carrying lytA and 6 strains negative for lytA) were both 100%. In patients with pneumococcal and non-pneumococcal pneumonia a cut-off value of 6.000 copies/mL would lead to a sensitivity of 57.1% and a specificity of 85.7%. We were able to develop a quantitative PCR targeting lytA with good in-vitro test characteristics.


Assuntos
Boca/microbiologia , Faringe/microbiologia , Pneumonia Pneumocócica/diagnóstico , Pneumonia Pneumocócica/microbiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Curva ROC , Reprodutibilidade dos Testes , Adulto Jovem
12.
Rev Med Chil ; 146(7): 839-845, 2018 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-30534882

RESUMO

BACKGROUND: Bacteremic pneumococcal pneumonia (BPP) is a preventable disease with high morbimortality. AIM: To evaluate clinical aspects and mortality on BPP patients admitted to a Chilean regional hospital. PATIENTS AND METHODS: We looked for adult patients with Streptococcus pneumoniae isolated from blood cultures between 2010 and 2014 years and reviewed clinical records of those who were admitted with pneumonia. RESULTS: We identified 70 BPP patients: 58% were men, mean age was 56 years, 30% were > 65 years, 70% with basic public health insurance, 26% were alcoholics, 86% had comorbidities. Only two patients were vaccinated against S. pneumoniae. CURB-65 severity index for community acquired pneumonia was > 3 in 37% of patients. Twenty-four patients were admitted to ICU, twenty required mechanical ventilation and twenty-four died (34%). Mortality was associated with an age over 65 years, presence of comorbidities and complications of pneumonia. A total of 22 serotypes of S. pneumoniae were identified, five of them (1,3,7F,14 y 9V) were present in 57% of cases. CONCLUSIONS: Elevated mortality of our BNN patients was associated with comorbidities and possibly with socio economic factors, which conditioned a late access to medical care.


Assuntos
Bacteriemia/mortalidade , Pneumonia Pneumocócica/mortalidade , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Ceftriaxona/uso terapêutico , Chile/epidemiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/mortalidade , Comorbidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Pneumocócica/diagnóstico , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/microbiologia , Fatores de Risco , Índice de Gravidade de Doença , Fatores Socioeconômicos , Streptococcus pneumoniae/isolamento & purificação
13.
PLoS One ; 13(11): e0206661, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30395582

RESUMO

Respiratory tract infections and invasive disease caused by Streptococcus pneumoniae in high-risk groups are a major global health problem. Available human vaccines have reduced immunogenicity and low immunological memory in these populations, as well as high cost as a public health strategy in poor communities. In addition, no single pneumococcal protein antigen has been able to elicit protection comparable to that achieved using protein-polysaccharide conjugate vaccines. In this context, chimeric pneumococcal proteins raise as potential good vaccine candidates because of their simplicity of production and reduced cost. The aim of this work was to study whether the nasal immunization of infant mice with the recombinant chimeric pneumococcal protein (PSFP) was able to improve resistance to S. pneumoniae, and whether the immunomodulatory strain Lactobacillus rhamnosus CRL1505 or its cell wall (CW1505) could be used as effective mucosal adjuvants. Our results showed that the nasal immunization with PSPF improved pneumococcal-specific IgA and IgG levels in broncho-alveolar lavage (BAL), reduced lung bacterial counts, and avoided dissemination of pneumococci into the blood. Of interest, immunization with PSPF elicited cross-protective immunity against different pneumococcal serotypes. It was also observed that the nasal immunization of infant mice with PSPF+CW1505 significantly increased the production of pneumococcal-specific IgA and IgG in BAL, as well as IgM and IgG in serum when compared with PSPF alone. PSPF+CW1505 immunization also improved the reduction of pneumococcal lung colonization and its dissemination in to the bloodstream when compared to PSPF alone. Our results suggest that immunization with PSPF together with the cell wall of the immunomodulatory strain L. rhamnosus CRL1505 as a mucosal adjuvant could be an interesting alternative to improve protection against pneumococcal infection in children.


Assuntos
Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Administração Intranasal , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/administração & dosagem , Proteínas de Bactérias/administração & dosagem , Proteínas de Bactérias/imunologia , Parede Celular/imunologia , Criança , Proteção Cruzada , Citocinas/sangue , Humanos , Imunidade nas Mucosas , Imunização , Lactobacillus rhamnosus/imunologia , Pulmão/imunologia , Pulmão/microbiologia , Masculino , Camundongos , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/imunologia , Pneumonia Pneumocócica/imunologia , Pneumonia Pneumocócica/microbiologia , Pneumonia Pneumocócica/prevenção & controle , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/imunologia , Streptococcus pneumoniae/imunologia
14.
PLoS One ; 13(11): e0206912, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30388168

RESUMO

Non-invasive pneumococcal pneumonia (NIPP) is a frequent cause of morbidity and mortality worldwide. The 13-valent pneumococcal conjugate vaccine (PCV13) was included in the national immunization program of children living in Portugal in 2015. Until then, PCV7 (since late 2001) and PCV13 (since early 2010) were given through the private market. We determined the serotype distribution and antimicrobial susceptibility of isolates causing adult NIPP in 2012-2015 and compared the results with previously published data (2007-2011). There were 50 serotypes among the 1435 isolates. The most common were serotypes: 3 (14%), 11A (8%), 19F (6%), 23A (5%), 6C (5%), 19A (4%), 23B (4%), 9N (4%) and non-typable isolates (4%). When considering data since the availability of PCV13 for children in the private market, the proportion of PCV13 serotypes declined from 44.0% in 2010 to 29.7% in 2015 (p < 0.001), mainly due to early decreases in the proportions of serotypes 3 and 19A. In contrast, during the same period, PCV7 serotypes (11.9% in 2012-2015) and the serotypes exclusive of the 23-valent polysaccharide vaccine (26.0% in 2012-2015), remained relatively stable, while non-vaccine types increased from 27.0% in 2010 to 41.9% in 2015 (p<0.001). According to the Clinical and Laboratory Standards Institute (CLSI) breakpoints, penicillin non-susceptible and erythromycin resistant isolates accounted for 1% and 21.7%, respectively, of the isolates recovered in 2012-2015, with no significant changes seen since 2007. Comparison of NIPP serotypes with contemporary invasive disease serotypes identified associations of 19 serotypes with either disease presentation. The introduction of PCV13 in the national immunization program for children from 2015 onwards may lead to reductions in the proportion of NIPP due to vaccine serotypes but continued NIPP surveillance is essential due to a different serotype distribution from invasive disease.


Assuntos
Infecções Pneumocócicas/tratamento farmacológico , Vacinas Pneumocócicas/uso terapêutico , Pneumonia Pneumocócica/tratamento farmacológico , Vacinas Conjugadas/uso terapêutico , Adolescente , Adulto , Idoso , Farmacorresistência Bacteriana/imunologia , Eritromicina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/efeitos dos fármacos , Nasofaringe/microbiologia , Nasofaringe/patologia , Penicilinas/uso terapêutico , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/prevenção & controle , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/microbiologia , Pneumonia Pneumocócica/prevenção & controle , Portugal/epidemiologia , Sorogrupo , Sorotipagem , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/patogenicidade , Adulto Jovem
15.
PLoS One ; 13(10): e0206305, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30339709

RESUMO

Streptococcus pneumoniae colonization is a precursor to pneumococcal disease. Although children with a tracheostomy have an increased risk of pneumococcal pneumonia, the pneumococci colonizing their lower airways remain largely uncharacterized. We sought to compare lower respiratory tract isolates colonizing tracheostomy patients and a convenience sample of isolates from individuals intubated for acute conditions. We collected pneumococcal isolates from the lower respiratory tract of 27 patients with a tracheostomy and 42 patients intubated for acute conditions. We compared the penicillin susceptibility, rates of co-colonization, genetic background, and serotype of isolates colonizing these patient populations. Isolates from both groups showed high genetic diversity. Forty multi-locus sequence types and 20 serotypes were identified. There was no significant difference in serotype distribution, co-colonization rates, vaccine coverage, or non-susceptibility to penicillin among pneumococcal isolates from the two groups. Colonization of the lower airways with non-vaccine serotypes 15B/C, 23B and 35B was noted for the first time in patients with tracheostomies and supports recently observed increases in nasopharyngeal colonization and disease due to these serotypes.


Assuntos
Intubação Intratraqueal , Pneumonia Pneumocócica/microbiologia , Streptococcus pneumoniae/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Farmacorresistência Bacteriana , Feminino , Humanos , Lactente , Masculino , Nasofaringe/microbiologia , Penicilinas/farmacologia , Penicilinas/uso terapêutico , Vacinas Pneumocócicas/imunologia , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/prevenção & controle , Insuficiência Respiratória/terapia , Estudos Retrospectivos , Sorogrupo , Streptococcus pneumoniae/efeitos dos fármacos , Traqueostomia
16.
Pathog Dis ; 76(7)2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30285091

RESUMO

Haemophilus influenzae and Streptococcus pneumoniae are known aetiologic agents of chronic otitis media, frequently as a multispecies infection. In this study, we show that the outcome of H. influenzae/S. pneumoniae interactions is dependent on the nutrient source. In continuous culture containing chemically defined media with lactose, S. pneumoniae was non-viable in mono-culture, and in co-culture remained non-viable until 288 h. With glucose, S. pneumoniae became non-viable in mono-culture, but uniquely existed in 3 distinct states in co-culture: parental cells (until 24 h), a dormant state until 336 h and its re-emergence as a non-mucoidal, small colony variant (SCV). The S. pneumoniae SCV was stable and whole genome sequencing showed three major single nucleotide polymorphisms in the SCV cells-cap3A (capsule biosynthesis pathway), fpg (DNA glycosylase of the DNA repair mechanism) and glutamate-5-kinase. Previously, fpg mutants have shown increased mutator rates, permitting bacterial survival against host-generated stresses. Transcriptomics showed these SCV cells up-regulated sugar transporters and toxin/antitoxin systems. An animal model revealed a reduced survival in the lungs and ear by SCV cells. This is the first study documenting the effect of carbon source and the development of a distinct S. pneumoniae cell type during H. influenzae/S. pneumoniae interactions.


Assuntos
Haemophilus influenzae/crescimento & desenvolvimento , Interações Microbianas , Polissacarídeos Bacterianos/metabolismo , Streptococcus pneumoniae/crescimento & desenvolvimento , Animais , Técnicas Bacteriológicas , Técnicas de Cocultura , Meios de Cultura/química , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Genes Bacterianos , Viabilidade Microbiana , Mutação , Pneumonia Pneumocócica/microbiologia , Pneumonia Pneumocócica/patologia , Polimorfismo de Nucleotídeo Único , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/metabolismo , Virulência , Sequenciamento Completo do Genoma
17.
Hum Vaccin Immunother ; 14(10): 2527-2532, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30188760

RESUMO

BACKGROUND: Community acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide, and is a leading cause of hospitalization in previously healthy individuals without predisposing risk factors or comorbidities. In this study we determined PCV13 serotype distribution in adults aged ≥50 years with radiographically confirmed CAP in Israel. METHODS: Subjects aged ≥50 years were enrolled from one of three hospitals (Emek Medical Center, Meir Medical Center and Sheba Medical Center) from March 2014 to July 2015. Information was collected on subject demographics, comorbidities, risk factors, and pneumococcal vaccine immunization status. Subjects presented with suspected CAP supported by radiographic evidence, and provided a urine sample and informed consent. Subjects without radiographic confirmation of CAP or who received PPSV23 within 30 days of study enrollment were excluded from the final analysis. Serotype distribution was performed using the urinary antigen detection (UAD) assay and/or microbiological culture. RESULTS: Overall, 498 subjects with radiographically confirmed CAP were enrolled in the study. Eighty subjects (16.1%) were positive for any S. pneumoniae serotype by ≥1 assay, and 38 (7.6%) were positive for PCV13 serotypes via the UAD. The overall 30-day mortality rate was 1.2%, though S. pneumoniae was not isolated from any case leading to death. CONCLUSION: Despite six years of high pneumococcal immunization coverage in children in Israel, we have shown that 7.6% of CAP cases among adults in Israel remain related to PCV13 serotypes; and that the burden of PCV13 may be as high as 47% of observed pneumococcal CAP.


Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Vacinas Pneumocócicas/imunologia , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/microbiologia , Sorogrupo , Streptococcus pneumoniae/classificação , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Vacinas Pneumocócicas/administração & dosagem , Prevalência , Streptococcus pneumoniae/isolamento & purificação
18.
Chembiochem ; 19(22): 2380-2386, 2018 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-30211457

RESUMO

Streptococcus pneumoniae (pneumococcus) is a prevalent human pathogen responsible for a variety of diseases, including pneumonia, bacteremia, sepsis, meningitis and otitis media, with a death toll of >22 000 a year in the United States alone. Pneumococcus uses the competence regulon and its associated signaling peptide, the competence stimulating peptide (CSP), to initiate its attack on the host and establish an infection. In this work, we set out to: 1) develop a pan-group quorum sensing inhibitor that could effectively interact with both the pneumococcus ComD1 and ComD2 receptors; and 2) evaluate the utility of dominant-negative CSPs (dnCSPs) in attenuating pneumococcus infectivity. Our results highlight the potential of inhibiting the competence regulon as a therapeutic approach to combat pneumococcus infections.


Assuntos
Proteínas de Bactérias , Pneumonia Pneumocócica , Percepção de Quorum/efeitos dos fármacos , Streptococcus pneumoniae , Doença Aguda , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/farmacologia , Modelos Animais de Doenças , Humanos , Camundongos , Terapia de Alvo Molecular , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidade , Virulência
19.
Cytokine ; 112: 75-86, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30077545

RESUMO

Streptococcus pneumoniae, a Gram-positive bacterium, can cause a broad range of severe diseases including pneumonia, septicemia and meningitis. The pneumococcal pathophysiology is highly dependent on host nutrients such as purines, pyrimidines, amino acids and carbon sources. The study of S. pneumoniae metabolism is essential for understanding the adaption strategies that are required to deal with the host environment during infection and to identify possible new drug targets. By using a combination of high analytical techniques, such as nuclear magnetic resonance (NMR), liquid chromatography (LC) and/or gas chromatography (GC) coupled with mass spectroscopy (MS) the metabolism of S. pneumoniae can be precisely investigated. This review summarizes the metabolism and major virulence factors of S. pneumoniae within the context of infection. Furthermore, it addresses the antibiotic resistance and its influence on metabolism as well as new antimicrobial substances for the treatment of S. pneumoniae.


Assuntos
Pneumonia Pneumocócica/metabolismo , Streptococcus pneumoniae/metabolismo , Fatores de Virulência/metabolismo , Aminoácidos/metabolismo , Animais , Anti-Infecciosos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos
20.
PLoS One ; 13(7): e0200620, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30028834

RESUMO

BACKGROUND: The pneumococcal urinary antigen test (UAT) has been known to improve sensitivity and specificity for the diagnosis of pneumococcal pneumonia. Associations of UAT results with prognosis in community acquired pneumonia (CAP) are not known. We hypothesized that positive UAT is associated with a good prognosis, and incorporation of UAT into CRB65 would improve its prognostic performance. METHODS: In this registry-based retrospective study, we analyzed CAP patients over a 10-year period beginning in April 2008. Patients who had UAT results were included in multivariable extended Cox-regression analyses to determine the association between UAT positivity and 30-day mortality. UAT results were incorporated for patients with a CRB65 score of 1 by subtracting 1 from the scoring system if the test was positive. The performance of the modified scoring systems was assessed with area under the receiver operating characteristic (AUROC) curves. RESULTS: Among 5145 CAP patients, total 2280 patients had UAT results and were included in analyses. A positive UAT result was associated with a good prognosis after a week of hospitalization (aHR, 0.14; p = 0.007). After modification of CRB65 using UAT results, positive and negative predictive values for 30-day mortality were increased from 7.7 to 8.3 (p<0.001) and 98.9 to 99.1 (p = 0.010). The AUROC increased from 0.73 to 0.75 (p<0.001). CONCLUSIONS: Positive results on UAT could be considered as a good prognostic factor in CAP. UAT could be used as a useful tool in deciding whether to refer patients to the hospital, especially in moderate CAP with a CRB score of 1.


Assuntos
Antígenos de Bactérias/urina , Infecções Comunitárias Adquiridas/mortalidade , Pneumonia Pneumocócica/mortalidade , Streptococcus pneumoniae/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Pneumocócica/diagnóstico , Pneumonia Pneumocócica/microbiologia , Pneumonia Pneumocócica/urina , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , República da Coreia/epidemiologia , Estudos Retrospectivos , Streptococcus pneumoniae/imunologia , Taxa de Sobrevida
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