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1.
BMC Pediatr ; 21(1): 265, 2021 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090356

RESUMO

BACKGROUND: Spontaneous infection of preexisting solitary renal cysts has been documented in adults but is extremely rare in children. To date, no cases of simple renal cysts infected with Streptococcus pneumoniae have been described. Recently, reports have described the diagnosis of bacterial infection using the 16 S rRNA gene as well as the accompanying antimicrobial stewardship for microorganisms that are difficult to culture and for culture-negative cases after preceding antibacterial administration. CASE PRESENTATION: A four-year-old Japanese girl who had a pleuroperitoneal shunt inserted to drain a right pleural effusion due to occlusion of the hepatic portion of the inferior vena cava at three years old visited our hospital due to fever and respiratory discomfort. She was incidentally found to have a right simple renal cyst 10 months before admission. The patient was suspected to have pneumonitis or catheter-related blood stream infection on chest X-ray, which showed right-side pleural effusion. She was diagnosed with invasive pneumococcal infection, as Streptococcus pneumoniae was detected from blood culture on admission. Transient improvements in her symptoms and decreases in the white blood cell count and C-reactive protein level were observed after effective antibiotic administration, but her respiratory condition deteriorated. Enhanced CT showed right renal cyst enlargement and enhancement and thickening of the surrounding wall. Using the melting temperature (Tm) mapping method, S. pneumoniae was rapidly detected directly from pus 4.5 hours after drainage. The specimen culture was negative, but the extracted 16 S rDNA sequence revealed 100 % identity for S. pneumoniae from the same specimen the subsequent day. We successfully performed optimal treatment and reduced medical cost based on the positive Tm mapping method result. CONCLUSIONS: We report the first case of a S. pneumoniae-infected simple renal cyst. The drainage culture was negative, but the Tm mapping method rapidly detected S. pneumoniae directly from the drainage. The Tm mapping method may have great impacts on rapid diagnosis and effective antimicrobial stewardship.


Assuntos
Doenças Renais Císticas , Derrame Pleural , Infecções Pneumocócicas , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Infecções Pneumocócicas/complicações , Infecções Pneumocócicas/diagnóstico , Infecções Pneumocócicas/tratamento farmacológico , Streptococcus pneumoniae/genética , Termografia
2.
BMC Infect Dis ; 21(1): 421, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952197

RESUMO

BACKGROUND: Streptococcus pneumoniae serotype 8 incidence has increased in Denmark after the introduction of pneumococcal conjugated vaccines (PCV). The mechanism behind the serotype 8 replacement is not well understood. In this study, we aimed to present epidemiological data on invasive pneumococcal disease (IPD) and molecular characterization of 96 serotype 8 clinical isolates. METHODS: IPD data from 1999 to 2019 were used to calculate the incidence and age distribution. Whole-genome sequencing (WGS) analysis was performed on 96 isolates (6.8% of the total serotype 8 IPD isolates in the period) to characterize the isolates with respect to pneumococcal lineage traits, a range of genes with potential species discrimination, presence of colonization and virulence factors, and molecular resistance pattern. RESULTS: The serotype 8 IPD incidence increased significantly (P < 0.05) for the age groups above 15 years after the introduction of PCV13, primarily affecting the elderly (65+). All isolates were phenotypically susceptible to penicillin, erythromycin and clindamycin. Molecular characterization revealed seven different MLST profiles with ST53 as the most prevalent lineage (87.5%) among the analyzed serotype 8 isolates. The genes covering the cell-surface proteins: lytA, rspB, pspA, psaA & Xisco and the pneumococcal toxin pneumolysin = ply were present in all isolates, while genes for the membrane transporter proteins: piaA/piaB/piaC; the capsular genes: cpsA (wzg) & psrP; the metallo-binding proteins zmpB & zmpC; and the neuroamidase proteins: nanA/nanB were variably present. Surprisingly, the putative transcriptional regulator gene SP2020 was not present in all isolates (98%). Susceptibility to penicillin, erythromycin and clindamycin was molecularly confirmed. CONCLUSION: The observed serotype 8 replacement was not significantly reflected with a change in the MLST profile or changes in antibiotic resistance- or virulence determinants.


Assuntos
Resistência Microbiana a Medicamentos/genética , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Dinamarca/epidemiologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Genes Bacterianos , Humanos , Incidência , Lactente , Proteínas de Membrana Transportadoras/genética , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Vacinas Pneumocócicas/farmacologia , Sorogrupo , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação , Vacinação , Vacinas Conjugadas/farmacologia , Fatores de Virulência/genética , Adulto Jovem
3.
Int J Mol Sci ; 22(9)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33925509

RESUMO

The structure of the exopolysaccharide capsule of Streptococcus pneumoniae is defined by the genetic arrangement of the capsule operon allowing the unequivocal identification of the pneumococcal serotype. Here, we investigated the environment-dependent composition of the polysaccharide structure of S. pneumoniae serotype 6F. When grown in a chemically defined medium (CDM) with glucose versus galactose, the exopolysaccharide capsule of the serotype 6F strains reveals a ratio of 1/0.6 or 1/0.3 for galactose/glucose in the capsule by 1H-NMR analyses, respectively. Increased production of the capsule precursor UDP-glucose has been identified by 31P-NMR in CDM with glucose. Flow cytometric experiments using monoclonal antibodies showed decreased labelling of Hyp6AG4 (specific for serotype 6A) antibodies when 6F is grown in glucose as compared to galactose, which mirrors the 1H-NMR results. Whole-genome sequencing analyses of serotype 6F isolates suggested that the isolates evolved during two different events from serotype 6A during the time when the 13-valent pneumococcal conjugate vaccine (PCV-13) was introduced. In conclusion, this study shows differences in the capsular structure of serotype 6F strains using glucose as compared to galactose as the carbon source. Therefore, 6F strains may show slightly different polysaccharide composition while colonizing the human nasopharynx (galactose rich) as compared to invasive locations such as the blood (glucose rich).


Assuntos
Carbono/metabolismo , Polissacarídeos Bacterianos/química , Streptococcus pneumoniae/química , Streptococcus pneumoniae/genética , Anticorpos Monoclonais/metabolismo , Evolução Biológica , Citometria de Fluxo , Galactose/metabolismo , Genoma Bacteriano , Glucose/metabolismo , Humanos , Espectroscopia de Ressonância Magnética/métodos , Nasofaringe/microbiologia , Fósforo , Filogenia , Infecções Pneumocócicas/microbiologia , Sorogrupo , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação
4.
Int J Infect Dis ; 105: 695-701, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33676003

RESUMO

OBJECTIVES: The emergence and spread of nonencapsulated Streptococcus pneumoniae (NESp) is a public health concern in the post-pneumococcal conjugate vaccine era. We analyzed the prevalence, molecular characteristics, and antimicrobial resistance of NESp responsible for noninvasive infections in northern Japan. METHODS: NESp isolates were identified using molecular and phenotypical methods among 4463 S. pneumoniae isolates from noninvasive infection cases during 4 study periods between January 2011 and January 2019. NESp isolates were analyzed for antimicrobial susceptibility, genotype, and virulence-associated genes. RESULTS: Seventy-one NESp isolates were identified (1.6% of total clinical isolates) and assigned to the null capsule clade (NCC)1 (pspK+) (94.4%) or NCC2 (aliC+/aliD+) (5.6%). The dominant sequence types (STs) were ST7502 (23.9%), ST4845 (19.7%), ST16214 (11.3%), ST11379 (9.9%), and ST7786 (7.0%). These 5 dominant STs and all 7 novel STs were related to the sporadic NESp lineage ST1106 or PMEN clone Denmark14-ST230. High non-susceptibility rates of NESp were observed for trimethoprim-sulfamethoxazole, erythromycin, and tetracycline (>92.9%), and multidrug resistance was observed in 88.7% of the NESp isolates, including all ST7502, ST4845, and ST11379 isolates. CONCLUSIONS: The study revealed that the dominant clonal groups of NESp were associated with a high prevalence of non-susceptibility to antimicrobials in northern Japan.


Assuntos
Farmacorresistência Bacteriana/genética , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Streptococcus pneumoniae/genética , Adolescente , Adulto , Antibacterianos/uso terapêutico , Criança , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Japão/epidemiologia , Testes de Sensibilidade Microbiana/métodos , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/genética , Prevalência , Streptococcus pneumoniae/isolamento & purificação , Vacinas Conjugadas/uso terapêutico , Virulência , Fatores de Virulência/genética
5.
Vaccine ; 39(9): 1392-1401, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33531198

RESUMO

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is an important pathogen causing both invasive and non-invasive infections in children, with significant morbidity and mortality worldwide. This study aimed to determine the potential relationships between age and vaccine coverage and between multiple phenotype-genotype characteristics of S. pneumoniae isolated from children. METHODS: All S. pneumoniae isolates were tested for antimicrobial susceptibility, virulence genes, serotypes, and sequence types. The restricted cubic spline models were used to reveal potential relationships between children age and pneumococcal vaccine coverage. RESULTS: For capsular-based vaccines, we observed a high coverage rate of 13-valent pneumococcal conjugate vaccine (PCV13, 85.8%) and a significantly non-linear relationship between children age and vaccine coverage (including PCV7, PCV10, and PCV13), with marked fluctuations in children aged < 2 years. For protein-based and pilus-based vaccine candidates, we demonstrated dynamic non-linear relationships between age and vaccine coverage, maintaining a stable and high coverage rate of ply and lytA for all age groups. Moreover, there were significantly high-dimensional corresponding relationships among multiple phenotype-genotype characteristics of S. pneumoniae isolates (such as ST271 associated with serotype 19F, PI-2, and extensively drug-resistance). CONCLUSIONS: Our findings suggest that the age for high PCV coverage being children aged ≥ 2 years and also provide important evidence for supporting ply and lytA as priority candidate targets for the development of new-generation protein vaccines.


Assuntos
Infecções Pneumocócicas , Criança , Pré-Escolar , Humanos , Lactente , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Sorogrupo , Sorotipagem , Streptococcus pneumoniae/genética , Vacinas Conjugadas , Virulência
6.
Appl Environ Microbiol ; 87(6)2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33397704

RESUMO

CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against viruses and plasmids by the detection and cleavage of invading foreign DNA. Modified versions of this system can be exploited as a biotechnological tool for precise genome editing at a targeted locus. Here, we developed a replicative plasmid that carries the CRISPR-Cas9 system for RNA-programmable genome editing by counterselection in the opportunistic human pathogen Streptococcus pneumoniae Specifically, we demonstrate an approach for making targeted markerless gene knockouts and large genome deletions. After a precise double-stranded break (DSB) is introduced, the cells' DNA repair mechanism of homology-directed repair (HDR) is exploited to select successful transformants. This is achieved through the transformation of a template DNA fragment that will recombine in the genome and eliminate recognition of the target of the Cas9 endonuclease. Next, the newly engineered strain can be easily cured from the plasmid, which is temperature sensitive for replication, by growing it at the nonpermissive temperature. This allows for consecutive rounds of genome editing. Using this system, we engineered a strain with three major virulence factors deleted. The approaches developed here could potentially be adapted for use with other Gram-positive bacteria.IMPORTANCE Streptococcus pneumoniae (the pneumococcus) is an important opportunistic human pathogen killing more than 1 million people each year. Having the availability of a system capable of easy genome editing would significantly facilitate drug discovery and efforts to identify new vaccine candidates. Here, we introduced an easy-to-use system to perform multiple rounds of genome editing in the pneumococcus by putting the CRISPR-Cas9 system on a temperature-sensitive replicative plasmid. The approaches used here will advance genome editing projects in this important human pathogen.


Assuntos
Proteína 9 Associada à CRISPR , Sistemas CRISPR-Cas , Edição de Genes/métodos , Streptococcus pneumoniae/genética , Proteínas de Bactérias/genética , Genoma Bacteriano , Fatores de Virulência/genética
7.
BMC Infect Dis ; 21(1): 45, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33423657

RESUMO

BACKGROUND: The Taiwanese national 23-valent pneumococcal polysaccharide vaccine (PPV23) program in adults ≥75 years of age and the 13-valent pneumococcal conjugate vaccine (PCV13) program for children were implemented in 2008 and 2013, respectively. In this study we evaluated PPV23 vaccine effectiveness (PPV23VE) in the elderly, with regard to both direct protection from the vaccine itself and the indirect protection conferred by PCV13 immunization in children. METHODS: The incidence of invasive pneumococcal disease (IPD) in Taiwan from July 2008 to June 2016 was collected from IPD surveillance data. A comparison of IPD incidence with a nationwide vaccination registry allowed an estimation of PPV23VE by the screening and indirect cohort methods. RESULTS: The incidence of IPD in adults ≥75 years of age ranged from 13.9 per 100,000 inhabitants during the period July 2008-June 2013 to 10.4 per 100,000 inhabitants between July 2013 and June 2016 (relative risk [RR]: 0.75; 95% confidence interval [95% CI]: 0.67-0.85). According to the screening method, PPV23VE against death within 30 days of IPD onset, all IPD, and PPV23-serotype IPD was 32.5% (95% CI: 17.5-44.7%), 33.9% (95% CI: 25.2-41.5%) and 43.4% (95% CI: 34.4-51.2%), respectively. PPV23VE with the indirect cohort method was 39.0% (95% CI: 15.5-55.9%) for all PPV23 serotypes and 71.5% (95% CI: 44.2-85.4%) for 11 serotypes included in PPV23 but not in PCV13. During the period July 2008-June 2012, PPV23VE against PPV23-serotype IPD was 55.1% (95% CI: 27.2-72.3%). CONCLUSIONS: PPV23 is able to prevent IPD and 30-day fatality in adults 75 years of age and older due to a combination of direct effects from PPV23 and indirect effects from PCV13. It might confer higher protection against PPV23-serotype IPD before the introduction of PCV13 program in children.


Assuntos
Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Programas de Imunização , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Avaliação de Programas e Projetos de Saúde , Sistema de Registros , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/genética , Taiwan/epidemiologia , Adulto Jovem
8.
ISME J ; 15(5): 1523-1538, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33408365

RESUMO

Streptococcus pneumoniae can be divided into many strains, each a distinct set of isolates sharing similar core and accessory genomes, which co-circulate within the same hosts. Previous analyses suggested the short-term vaccine-associated dynamics of S. pneumoniae strains may be mediated through multi-locus negative frequency-dependent selection (NFDS), which maintains accessory loci at equilibrium frequencies. Long-term simulations demonstrated NFDS stabilised clonally-evolving multi-strain populations through preventing the loss of variation through drift, based on polymorphism frequencies, pairwise genetic distances and phylogenies. However, allowing symmetrical recombination between isolates evolving under multi-locus NFDS generated unstructured populations of diverse genotypes. Replication of the observed data improved when multi-locus NFDS was combined with recombination that was instead asymmetrical, favouring deletion of accessory loci over insertion. This combination separated populations into strains through outbreeding depression, resulting from recombinants with reduced accessory genomes having lower fitness than their parental genotypes. Although simplistic modelling of recombination likely limited these simulations' ability to maintain some properties of genomic data as accurately as those lacking recombination, the combination of asymmetrical recombination and multi-locus NFDS could restore multi-strain population structures from randomised initial populations. As many bacteria inhibit insertions into their chromosomes, this combination may commonly underlie the co-existence of strains within a niche.


Assuntos
Polimorfismo Genético , Seleção Genética , Bactérias , Genótipo , Streptococcus pneumoniae/genética
9.
BMC Genomics ; 22(1): 39, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413118

RESUMO

BACKGROUND: Streptococcus pneumoniae serotype 1 remains a leading cause of invasive pneumococcal diseases, even in countries with PCV-10/PCV-13 vaccine implementation. The main objective of this study, which is part of the Pneumococcal African Genome project (PAGe), was to determine the phylogenetic relationships of serotype 1 isolates recovered from children patients in Casablanca (Morocco), compared to these from other African countries; and to investigate the contribution of accessory genes and recombination events to the genetic diversity of this serotype. RESULTS: The genome average size of the six-pneumococcus serotype 1 from Casablanca was 2,227,119 bp, and the average content of coding sequences was 2113, ranging from 2041 to 2161. Pangenome analysis of the 80 genomes used in this study revealed 1685 core genes and 1805 accessory genes. The phylogenetic tree based on core genes and the hierarchical bayesian clustering analysis revealed five sublineages with a phylogeographic structure by country. The Moroccan strains cluster in two different lineages, the five invasive strains clusters altogether in a divergent clade distantly related to the non-invasive strain, that cluster with all the serotype 1 genomes from Africa. CONCLUSIONS: The whole genome sequencing provides increased resolution analysis of the highly virulent serotype 1 in Casablanca, Morocco. Our results are concordant with previous works, showing that the phylogeography of S. pneumoniae serotype 1 is structured by country, and despite the small size (six isolates) of the Moroccan sample, our analysis shows the genetic cohesion of the Moroccan invasive isolates.


Assuntos
Infecções Pneumocócicas , Streptococcus pneumoniae , Teorema de Bayes , Criança , Pré-Escolar , Genômica , Humanos , Marrocos/epidemiologia , Filogenia , Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas , Sorogrupo , Sorotipagem , Streptococcus pneumoniae/genética
10.
Int J Infect Dis ; 104: 580-583, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33476756

RESUMO

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) of serogroup 19 are mainly represented by serotypes 19A and 19F, which are associated with antimicrobial resistance and disease. The wzy gene, a component of the pneumococcal capsular locus, is the target to differentiate serotypes 19A and 19F by PCR-based capsular typing. In the last decade, allelic variants of the wzy19F gene have been described, leading to misinterpretation of capsular typing results. METHODS: A collection of 154 serotype 19F S. pneumoniae strains recovered from carriage and disease in Brazil was evaluated to identify and characterize wzy19F variant isolates. RESULTS: Eleven (7%) wzy19F variant isolates were detected and identified as belonging to ST810 (n = 10) or ST13673 (n = 1; single-locus variant of ST810). They were mostly recovered from diseased patients, susceptible to the antimicrobial agents tested (except for one multidrug-resistant strain) and did not harbor pili genes. Sequences of the wzy19F gene of these variants were identical to each other and to those previously described in Brazil, but slightly different from wzy19F variants identified in other countries. CONCLUSION: This study indicated that wzy19F variants present a geographically driven distribution and was the first to uncover phenotypic and genetic features of a wzy19F variant lineage occurring in Brazil since 1989.


Assuntos
Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação , Alelos , Infecções Assintomáticas , Cápsulas Bacterianas/classificação , Cápsulas Bacterianas/genética , Brasil , Proteínas de Transporte/genética , Portador Sadio/microbiologia , Feminino , Variação Genética , Humanos , Masculino , Tipagem de Sequências Multilocus , Reação em Cadeia da Polimerase , Sorogrupo , Sorotipagem , Streptococcus pneumoniae/genética
12.
Carbohydr Polym ; 254: 117323, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33357884

RESUMO

Capsular polysaccharides (CPS) are the key virulent factors in the pathogenesis of Streptococcus pneumoniae. The previously unknown CPS structures of the pneumococcal serotype 28F and 28A were thoroughly characterized by NMR spectroscopy, chemical analysis and AF4-MALS-dRI. The following repeat unit structures were determined: -4)[α-l-Rhap-[4-P-2-Gro]]-(1-3)-α-d-Sug-[6-P-Cho]-(1-3)-ß-l-Rhap-[2-OAc]-(1-4)-ß-d-Glcp-(1-; 28F: Sug = Glcp, Mw: 540.5 kDa; 28A: Sug = GlcpNAc, Mw: 421.9 kDa; The correlation of CPS structures with biosynthesis showed that glycosyltransferase WciU in serotypes 28F and 28A had different sugar donor specificity toward α-d-Glcp and α-d-GlcNAcp, respectively. Furthermore, latex agglutination tests of de-OAc and de-PO4 CPS were conducted to understand cross-reactions between serogroup 28 with factor antiserum 23d. Interestingly, the de-OAc 28F and 28A CPS can still weakly react with factor antiserum 23d, while de-PO4 CPS did not react with factor antiserum 23d. This indicated that OAc group could affect the affinity and P-2-Gro was crucial for cross-reacting with factor antiserum 23d.


Assuntos
Cápsulas Bacterianas/química , Soros Imunes/imunologia , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/imunologia , Sorogrupo , Streptococcus pneumoniae/química , Streptococcus pneumoniae/genética , Sequência de Aminoácidos , Reações Cruzadas , Glicosiltransferases/química , Testes de Fixação do Látex , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Peso Molecular , Polissacarídeos Bacterianos/biossíntese
13.
Nihon Saikingaku Zasshi ; 75(2): 173-183, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33361653

RESUMO

This review summarizes current knowledge regarding the pathological mechanism of Streptococcus pneumoniae, a major cause of pneumonia, sepsis, and meningitis, with focus on our previously presented studies.To identify pneumococcal adhesins or invasins on cell surfaces, we investigated several proteins with an LPXTG anchoring motif and identified one showing interaction with human fibronectin, which was designated PfbA. Next, the mechanism of pneumococcal evasion form host immunity system in blood was examined and pneumococcal α-Enolase was found to function as a neutrophil extracellular trap induction factor. Although S. pneumoniae organisms are partially killed by iron ion-induced free radicals, they have an ability to invade red blood cells and then evade antibiotics, neutrophil phagocytosis, and H2O2 killing. In addition, our findings have indicated that zinc metalloprotease ZmpC suppresses pneumococcal virulence by inhibiting bacterial invasion of the central nervous system. Since evolutionarily conserved virulence factors are potential candidate therapeutic targets, we performed molecular evolutionary analyses, which revealed that cbpJ had the highest rate of codons under negative selection to total number of codons among genes encoding choline-binding proteins. Our experimental analysis results indicated that CbpJ functions as a virulence factor in pneumococcal pneumonia by contributing to evasion of neutrophil killing.Use of a molecular biological approach based on bacterial genome sequences, clinical disease states, and molecular evolutionary analysis is an effective strategy for revealing virulence factors and important therapeutic targets.


Assuntos
Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidade , Fatores de Virulência , Virulência , Animais , Proteínas de Bactérias/genética , Códon , Evolução Molecular , Humanos , Metaloendopeptidases/farmacologia , Camundongos , Terapia de Alvo Molecular , Neutrófilos/microbiologia , Fagocitose , Fosfopiruvato Hidratase , Infecções Pneumocócicas/tratamento farmacológico , Virulência/efeitos dos fármacos
14.
J Nippon Med Sch ; 87(5): 299-303, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33311009

RESUMO

In Japan, pneumococcal vaccine has been routinely administered since 2010 to prevent invasive pneumococcal diseases such as Streptococcus pneumoniae meningitis. We describe a case of pneumococcal meningitis in a 7-month-old girl who had received three doses of 13-valent pneumococcal conjugate vaccine. Brain magnetic resonance imaging showed infarcts in the right frontal region, and she was treated with antibiotics, intravenous immunoglobulin, dexamethasone, and edaravone. On day 27, an enhanced brain CT scan showed improvement of abnormal findings in the frontal region, except for slight atrophy. The S. pneumoniae serotype was 12F, which is not included in the 13-valent pneumococcal conjugate vaccine. A future vaccine is expected to use cross-reactivity to target common antigens.


Assuntos
Meningites Bacterianas/etiologia , Meningites Bacterianas/microbiologia , Infecções Pneumocócicas , Vacinas Pneumocócicas/efeitos adversos , Streptococcus pneumoniae , Vacinas Conjugadas/efeitos adversos , Antígenos de Bactérias/imunologia , Encéfalo/diagnóstico por imagem , Reações Cruzadas , Dexametasona/uso terapêutico , Edaravone/uso terapêutico , Feminino , Humanos , Imunoglobulinas Intravenosas , Lactente , Imageamento por Ressonância Magnética , Meningites Bacterianas/diagnóstico por imagem , Meningites Bacterianas/tratamento farmacológico , Infecções Pneumocócicas/prevenção & controle , Sorogrupo , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/imunologia , Tomografia Computadorizada por Raios X
15.
Nat Commun ; 11(1): 4365, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32868761

RESUMO

Current approaches explore bacterial genes that change transcriptionally upon stress exposure as diagnostics to predict antibiotic sensitivity. However, transcriptional changes are often specific to a species or antibiotic, limiting implementation to known settings only. While a generalizable approach, predicting bacterial fitness independent of strain, species or type of stress, would eliminate such limitations, it is unclear whether a stress-response can be universally captured. By generating a multi-stress and species RNA-Seq and experimental evolution dataset, we highlight the strengths and limitations of existing gene-panel based methods. Subsequently, we build a generalizable method around the observation that global transcriptional disorder seems to be a common, low-fitness, stress response. We quantify this disorder using entropy, which is a specific measure of randomness, and find that in low fitness cases increasing entropy and transcriptional disorder results from a loss of regulatory gene-dependencies. Using entropy as a single feature, we show that fitness and quantitative antibiotic sensitivity predictions can be made that generalize well beyond training data. Furthermore, we validate entropy-based predictions in 7 species under antibiotic and non-antibiotic conditions. By demonstrating the feasibility of universal predictions of bacterial fitness, this work establishes the fundamentals for potentially new approaches in infectious disease diagnostics.


Assuntos
Bactérias/genética , Evolução Molecular Direcionada , Farmacorresistência Bacteriana/genética , Estresse Fisiológico , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Fenômenos Fisiológicos Bacterianos , Doenças Transmissíveis/diagnóstico , Entropia , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos , Genoma Bacteriano , Análise de Sequência de RNA , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/metabolismo , Transcriptoma
16.
PLoS One ; 15(8): e0237871, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817720

RESUMO

Streptococcus pneumoniae is a common cause of infectious diseases such as pneumonia and sepsis. Its colonization is thought to be the first step in the development of invasive pneumococcal diseases. This study aimed to investigate pneumococcal colonization patterns in early childhood. A longitudinal birth cohort study was conducted for investigating nasopharyngeal colonized pneumococci at 1, 6, 12, 18, 24, and 36 months of age, particularly focusing on the serotype distribution and antimicrobial susceptibilities. Pneumococcal conjugate vaccine (PCV) effect on nasopharyngeal colonization was also assessed. During 2013-2017, 855 infants were enrolled and a total of 107 isolates were recovered from 95 infants during the first three years of life. In this period, the prevalence of pneumococcal colonization increased, with values ranging from 0.2% (2/834) at 1 month of age to 5.9% (19/323) at 36 months of age. The investigation of serotype revealed that 81.1% (73/90) belonged to the non-PCV13 serotypes-23A, 15A, 15C, and 15B. Moreover, PCV13 serotypes significantly decreased during 2014-2015, when routine PCV13 vaccination was initiated in Taiwan. PCV13 introduction may lead to the reduction in the rates of pneumococcal isolates resistant (R) to penicillin. Under conditional PCV13 vaccination, pneumococcal isolates primarily belonged to non-PCV13 serotypes. This non-PCV13 serotype replacement exhibited lower rates of penicillin R isolates, suggesting that PCV13 administration may reduce the antibiotic-nonsusceptible pneumococcal disease burden and antibiotic use.


Assuntos
Doenças Nasofaríngeas/tratamento farmacológico , Nasofaringe/efeitos dos fármacos , Infecções Pneumocócicas/tratamento farmacológico , Streptococcus pneumoniae/efeitos dos fármacos , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Doenças Nasofaríngeas/imunologia , Doenças Nasofaríngeas/microbiologia , Doenças Nasofaríngeas/patologia , Nasofaringe/microbiologia , Penicilinas/administração & dosagem , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/patologia , Vacinas Pneumocócicas/administração & dosagem , Pneumonia/microbiologia , Pneumonia/prevenção & controle , Sepse/microbiologia , Sepse/prevenção & controle , Sorogrupo , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidade , Taiwan , Vacinas Conjugadas/administração & dosagem
17.
PLoS Comput Biol ; 16(7): e1008010, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32628660

RESUMO

Antibiotic-resistant infections are a growing threat to human health, but basic features of the eco-evolutionary dynamics remain unexplained. Most prominently, there is no clear mechanism for the long-term coexistence of both drug-sensitive and resistant strains at intermediate levels, a ubiquitous pattern seen in surveillance data. Here we show that accounting for structured or spatially-heterogeneous host populations and variability in antibiotic consumption can lead to persistent coexistence over a wide range of treatment coverages, drug efficacies, costs of resistance, and mixing patterns. Moreover, this mechanism can explain other puzzling spatiotemporal features of drug-resistance epidemiology that have received less attention, such as large differences in the prevalence of resistance between geographical regions with similar antibiotic consumption or that neighbor one another. We find that the same amount of antibiotic use can lead to very different levels of resistance depending on how treatment is distributed in a transmission network. We also identify parameter regimes in which population structure alone cannot support coexistence, suggesting the need for other mechanisms to explain the epidemiology of antibiotic resistance. Our analysis identifies key features of host population structure that can be used to assess resistance risk and highlights the need to include spatial or demographic heterogeneity in models to guide resistance management.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Genética Populacional , Infecções Estreptocócicas/microbiologia , Algoritmos , Evolução Molecular , Geografia , Humanos , Modelos Teóricos , Prevalência , Análise de Regressão , Risco , Espanha/epidemiologia , Infecções Estreptocócicas/epidemiologia , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética
18.
Nat Commun ; 11(1): 3442, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32651390

RESUMO

Genomic evolution, transmission and pathogenesis of Streptococcus pneumoniae, an opportunistic human-adapted pathogen, is driven principally by nasopharyngeal carriage. However, little is known about genomic changes during natural colonisation. Here, we use whole-genome sequencing to investigate within-host microevolution of naturally carried pneumococci in ninety-eight infants intensively sampled sequentially from birth until twelve months in a high-carriage African setting. We show that neutral evolution and nucleotide substitution rates up to forty-fold faster than observed over longer timescales in S. pneumoniae and other bacteria drives high within-host pneumococcal genetic diversity. Highly divergent co-existing strain variants emerge during colonisation episodes through real-time intra-host homologous recombination while the rest are co-transmitted or acquired independently during multiple colonisation episodes. Genic and intergenic parallel evolution occur particularly in antibiotic resistance, immune evasion and epithelial adhesion genes. Our findings suggest that within-host microevolution is rapid and adaptive during natural colonisation.


Assuntos
Infecções Pneumocócicas/genética , Streptococcus pneumoniae/genética , Evolução Molecular , Genética , Genoma Bacteriano/genética , Humanos , Sequenciamento Completo do Genoma
19.
Int J Infect Dis ; 98: 113-120, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32562849

RESUMO

BACKGROUND: Streptococcus pneumoniae remains a major contributor to childhood infections and deaths globally. In Cameroon, the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in July 2011, using a 3-dose Expanded programme on immunization (EPI) schedule administered to infants at 6, 10 and 14 weeks of age. To evaluate PCV13 effects, we assessed pneumococcal nasopharyngeal colonization and serotype distribution among Cameroonian children after PCV13 introduction. METHODS: Nasopharyngeal (NP) swabs were collected from eligible children aged 24-36 months in two cross-sectional surveys conducted from March to July: in 2013 (PCV13-unvaccinated), and in 2015 (PCV13-vaccinated). Using a systematic World Health Organization (WHO) cluster coverage sampling technique in 40 communities, NP swabs collected were processed following WHO recommendations. Standard bacterial culture techniques were used for the isolation of S. pneumoniae from gentamicin-blood agar plates and identification using optochin susceptibility testing. Serotyping was performed using sequential multiplex polymerase chain reaction, supplemented with Quellung test. RESULTS: Among the PCV13-vaccinated children, overall pneumococcal carriage prevalence was 61.8% (426/689) and PCV13 vaccine-type carriage prevalence was 18.0% (123/689). Eleven out of the 13 vaccine serotypes were detected in the vaccinated children. The most common serotypes were 19F (4.5%, 31/689) and 15B/C (7.3%, 50/689). CONCLUSION: In Cameroon, four years after infant vaccination nearly all of the PCV13-serotypes continued to circulate in the population. This suggests that the direct and indirect effects of the vaccination programme have not resulted in expected low levels of vaccine-type transmission. Continuous monitoring is needed to assess the long term effects of the PCV13 on nasopharyngeal carriage and disease.


Assuntos
Nasofaringe/microbiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/imunologia , Camarões/epidemiologia , Portador Sadio/epidemiologia , Portador Sadio/imunologia , Portador Sadio/microbiologia , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Programas de Imunização , Esquemas de Imunização , Masculino , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/imunologia , Prevalência , Sorogrupo , Sorotipagem , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/crescimento & desenvolvimento , Streptococcus pneumoniae/isolamento & purificação , Vacinação
20.
Int J Infect Dis ; 97: 374-379, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32534142

RESUMO

OBJECTIVES: To report atypical pathogens from clinical trial data comparing delafloxacin to moxifloxacin in the treatment of adults with community-acquired bacterial pneumonia (CABP). METHODS: Multiple diagnostic methods were employed to diagnose atypical infections including culture, serology, and urinary antigen. RESULTS: The microbiological intent-to-treat (MITT) population included 520 patients; 30% had an atypical bacterial pathogen identified (156/520). Overall, 13.1% (68/520) had a monomicrobial atypical infection and 2.3% (12/520) had polymicrobial all-atypical infections. Among patients with polymicrobial infections, Streptococcus pneumoniae was the most frequently occurring co-infecting organism and Chlamydia pneumoniae was the most frequently occurring co-infecting atypical organism. For Mycoplasma pneumoniae and Legionella pneumophila, serology yielded the highest number of diagnoses. Delafloxacin and moxifloxacin had similar in vitro activity against M. pneumoniae and delafloxacin had greater activity against L. pneumophila. Two macrolide-resistant M. pneumoniae isolates were recovered. No fluoroquinolone-resistant M. pneumoniae were isolated. The rates of microbiological success (documented or presumed eradication) at test-of-cure were similar between the delafloxacin and moxifloxacin groups. There was no evidence of a correlation between minimum inhibitory concentration (MIC) and outcome; a high proportion of favorable outcomes was observed across all delafloxacin baseline MICs. CONCLUSIONS: Delafloxacin may be considered a treatment option as monotherapy for CABP in adults, where broad-spectrum coverage including atypical activity is desirable.


Assuntos
Antibacterianos/administração & dosagem , Infecções Comunitárias Adquiridas/tratamento farmacológico , Fluoroquinolonas/administração & dosagem , Moxifloxacina/administração & dosagem , Pneumonia Bacteriana/tratamento farmacológico , Adulto , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Humanos , Legionella pneumophila/efeitos dos fármacos , Legionella pneumophila/crescimento & desenvolvimento , Legionella pneumophila/isolamento & purificação , Macrolídeos/administração & dosagem , Masculino , Testes de Sensibilidade Microbiana , Mycoplasma pneumoniae/efeitos dos fármacos , Mycoplasma pneumoniae/crescimento & desenvolvimento , Mycoplasma pneumoniae/isolamento & purificação , Pneumonia Bacteriana/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação , Adulto Jovem
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