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1.
Nat Commun ; 11(1): 4697, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943639

RESUMO

Unassisted metastasis through the lymphatic system is a mechanism of dissemination thus far ascribed only to cancer cells. Here, we report that Streptococcus pyogenes also hijack lymphatic vessels to escape a local infection site, transiting through sequential lymph nodes and efferent lymphatic vessels to enter the bloodstream. Contrasting with previously reported mechanisms of intracellular pathogen carriage by phagocytes, we show S. pyogenes remain extracellular during transit, first in afferent and then efferent lymphatics that carry the bacteria through successive draining lymph nodes. We identify streptococcal virulence mechanisms important for bacterial lymphatic dissemination and show that metastatic streptococci within infected lymph nodes resist and subvert clearance by phagocytes, enabling replication that can seed intense bloodstream infection. The findings establish the lymphatic system as both a survival niche and conduit to the bloodstream for S. pyogenes, explaining the phenomenon of occult bacteraemia. This work provides new perspectives in streptococcal pathogenesis with implications for immunity.


Assuntos
Linfonodos/microbiologia , Metástase Linfática , Vasos Linfáticos/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/patogenicidade , Animais , Bacteriemia/microbiologia , Bacteriemia/patologia , Modelos Animais de Doenças , Feminino , Interleucina-8/metabolismo , Linfonodos/imunologia , Linfonodos/patologia , Metástase Linfática/patologia , Sistema Linfático , Vasos Linfáticos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neutrófilos/microbiologia , Fagocitose , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/patologia , Streptococcus pyogenes/genética , Virulência
2.
Nat Commun ; 11(1): 3545, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669564

RESUMO

Group A Streptococcus (GAS) infection causes a range of diseases, but vaccine development is hampered by the high number of serotypes. Here, using reverse vaccinology the authors identify SPy_2191 as a cross-protective vaccine candidate. From 18 initially identified surface proteins, only SPy_2191 is conserved, surface-exposed and inhibits both GAS adhesion and invasion. SPy_2191 immunization in mice generates bactericidal antibodies resulting in opsonophagocytic killing of prevalent and invasive GAS serotypes of different geographical regions, including M1 and M49 (India), M3.1 (Israel), M1 (UK) and M1 (USA). Resident splenocytes show higher interferon-γ and tumor necrosis factor-α secretion upon antigen re-stimulation, suggesting activation of cell-mediated immunity. SPy_2191 immunization significantly reduces streptococcal load in the organs and confers ~76-92% protection upon challenge with invasive GAS serotypes. Further, it significantly suppresses GAS pharyngeal colonization in mice mucosal infection model. Our findings suggest that SPy_2191 can act as a universal vaccine candidate against GAS infections.


Assuntos
Proteínas de Bactérias/imunologia , Proteção Cruzada/imunologia , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/imunologia , Streptococcus pyogenes/imunologia , Animais , Aderência Bacteriana/imunologia , Linhagem Celular , Clonagem Molecular , Modelos Animais de Doenças , Feminino , Humanos , Imunogenicidade da Vacina , Camundongos , Testes de Neutralização , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/imunologia , Sorogrupo , Infecções Estreptocócicas/microbiologia , Vacinas Estreptocócicas/administração & dosagem , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia
3.
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
5.
Cochrane Database Syst Rev ; 6: CD012431, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32497279

RESUMO

BACKGROUND: Sore throat is a common condition caused by viruses or bacteria, and is a leading cause of antibiotic prescription in primary care. The most common bacterial species is group A streptococcus ('strep throat'). Between 50% to 70% of pharyngitis cases are treated with antibiotics, despite the majority of cases being viral in origin. One strategy to reduce antibiotics is to use rapid tests for group A streptococcus to guide antibiotic prescriptions. Rapid tests can be used alone or in combination with a clinical scoring system. OBJECTIVES: To assess the efficacy and safety of strategies based on rapid tests to guide antibiotic prescriptions for sore throat in primary care settings. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Web of Science, and LILACS, as well as the trial registries ClinicalTrials.gov and the WHO ICTRP on 5 June 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing rapid tests with management based on clinical grounds to guide the prescription of antibiotics for people with a sore throat in ambulatory care settings. We included trials that randomised individuals, as well as cluster-RCTs in which individual practitioners (or practices) or emergency departments were randomised. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data on the primary outcomes (number of participants provided with an antibiotic prescription; number of participants with an antibiotic dispensed) and secondary outcomes (duration of sore throat symptoms; duration of other symptoms; quality of life measures; number of participants with a complication attributed to the index infection; number of participants in need of re-consultation by the end of follow-up; number of participants in need of hospital admission by the end of follow-up; number of satisfied participants; number of participants with an adverse event attributed to the rapid test). We assessed the risk of bias of all included trials and used GRADE to assess the certainty of the evidence. We performed meta-analyses and sensitivity analyses when feasible. MAIN RESULTS: We included five trials (2891 children and adult participants in total; 2545 participants after adjusting for clustering). Management in the intervention group was as follows: in three trials rapid tests were used in combination with a clinical scoring system; in one trial, some physicians were asked to use rapid tests alone, while others were asked to use rapid tests in combination with a clinical scoring system; in one trial, rapid tests were used alone. Based on data from five trials (2545 participants), a large reduction in prescribed antibiotics was found in the rapid test group (481/1197) versus management based on clinical grounds (865/1348), for a summary risk difference (RD) of -25%, 95% confidence interval (CI) -31% to -18%; I2 = 62%; moderate-certainty evidence. Estimates of effect on antibiotic prescription rates were stable in various sensitivity analyses. Based on data from two trials (900 people) originating from the same overarching study, the evidence suggests that rapid tests may not reduce dispensed antibiotic treatments: rapid test group (156/445) versus management based on clinical grounds (197/455); summary RD -7%, 95% CI -17% to 2%; I2 = 53%; low-certainty evidence. Four trials (2075 participants) reported data on the number of participants with a complication attributed to the index infection; the summary odds ratio (OR) was 0.85, 95% CI 0.03 to 26.65; P = 0.93; I2 = 62%; very low-certainty evidence, which means that people in the rapid testing group were less likely to develop complications of the index infection, but the evidence is very uncertain. Two trials (1161 participants) reported on the number of participants in need of re-consultation by the end of follow-up; the summary OR was 1.12, 95% CI 0.57 to 2.21; P = 0.74; I2 = 59%; low-certainty evidence, which means that participants in the rapid testing group were more likely to be in need of re-consultation by the end of the study follow-up, but the evidence is uncertain. Lack of data impeded assessment of other secondary outcomes (including safety outcomes) and of sources of heterogeneity.  AUTHORS' CONCLUSIONS: Rapid testing to guide antibiotic treatment for sore throat in primary care probably reduces antibiotic prescription rates by 25% (absolute risk difference), but may have little or no impact on antibiotic dispensing. More studies are needed to assess the efficacy and safety of rapid test-guided antibiotic prescribing, notably to evaluate patient-centred outcomes and variability across subgroups (e.g. adults versus children).


Assuntos
Antibacterianos/uso terapêutico , Faringite/tratamento farmacológico , Faringite/microbiologia , Infecções Estreptocócicas/diagnóstico , Streptococcus pyogenes/isolamento & purificação , Adulto , Técnicas Bacteriológicas , Criança , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Masculino , Faringite/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Estreptocócicas/microbiologia
6.
PLoS One ; 15(6): e0235139, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574205

RESUMO

Viral infections complicated by a bacterial infection are typically referred to as coinfections or superinfections. Streptococcus pyogenes, the group A streptococcus (GAS), is not the most common bacteria associated with influenza A virus (IAV) superinfections but did cause significant mortality during the 2009 influenza pandemic even though all isolates are susceptible to penicillin. One approach to improve the outcome of these infections is to use passive immunization targeting GAS. To test this idea, we assessed the efficacy of passive immunotherapy using antisera against either the streptococcal M protein or streptolysin O (SLO) in a murine model of IAV-GAS superinfection. Prophylactic treatment of mice with antiserum to either SLO or the M protein decreased morbidity compared to mice treated with non-immune sera; however, neither significantly decreased mortality. Therapeutic use of antisera to SLO decreased morbidity compared to mice treated with non-immune sera but neither antisera significantly reduced mortality. Overall, the results suggest that further development of antibodies targeting the M protein or SLO may be a useful adjunct in the treatment of invasive GAS diseases, including IAV-GAS superinfections, which may be particularly important during influenza pandemics.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas de Transporte/imunologia , Imunoterapia/métodos , Vírus da Influenza A/imunologia , Infecções por Orthomyxoviridae/imunologia , Infecções Estreptocócicas/imunologia , Streptococcus pyogenes/imunologia , Estreptolisinas/imunologia , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/metabolismo , Proteínas da Membrana Bacteriana Externa/antagonistas & inibidores , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/metabolismo , Coinfecção/microbiologia , Coinfecção/terapia , Coinfecção/virologia , Feminino , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Soros Imunes/imunologia , Soros Imunes/farmacologia , Vírus da Influenza A/fisiologia , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/terapia , Infecções por Orthomyxoviridae/virologia , Coelhos , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/terapia , Streptococcus pyogenes/metabolismo , Streptococcus pyogenes/fisiologia , Estreptolisinas/antagonistas & inibidores , Estreptolisinas/metabolismo , Superinfecção/microbiologia , Superinfecção/terapia , Superinfecção/virologia
7.
Arch Microbiol ; 202(8): 2071-2081, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32488560

RESUMO

Streptococcus intermedius is a causative agent of brain or liver abscesses. S. intermedius produces intermedilysin that plays a pivotal role in pathogenicity. We identified other pathogenic factors and described a fibronectin binding protein (FBP) homolog of S. intermedius (FbpI) that mediated bacterial adhesion to epithelial cells and virulence for mice. The amino acid sequence of FbpI is similar to that of atypical FBPs, which do not possess a conventional secretion signal and an anchoring motif. A full-length recombinant FbpI (rFbpI) bound to immobilized fibronectin in a dose-dependent manner. The fibronectin binding activity of an N-terminal construct of rFbpI comprising the translation initiation methionine of the open reading frame to lysine 265 (rFbpI-N) bound immobilized fibronectin to a much lesser extent compared with rFbpI. A construct comprising the C-terminal domain (alanine 266 to methionine 549; rFbpI-C) bound immobilized fibronectin equivalently to rFbpI. Adherence of the isogenic mutant ΔfbpI to cultured epithelial cells and immobilized fibronectin was significantly lower than that of the wild-type strain. Abscess formation of ΔfbpI reduced in a mouse infection model compared with that in the wild-type. Thus, FbpI may play a role in bacterial adhesion to host cells and represent a critical pathogenic factor of S. intermedius.


Assuntos
Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/patologia , Streptococcus intermedius/genética , Streptococcus intermedius/patogenicidade , Virulência/genética , Animais , Aderência Bacteriana , Bacteriocinas , Proteínas de Transporte/metabolismo , Modelos Animais de Doenças , Fibronectinas/metabolismo , Humanos , Camundongos , Ligação Proteica , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Streptococcus intermedius/metabolismo
8.
Arch Microbiol ; 202(8): 2023-2032, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32504132

RESUMO

Streptococcus pyogenes is a species of Gram-positive bacteria. It is also known as Group A Streptococcus (GAS) that causes pathogenesis to humans only. The GAS infection has several manifestations including invasive illness. Current research has linked the molecular modes of GAS virulence with substantial sequencing determinations for the isolation of genomes. These advances help to comprehend the molecular evolution resulting in the pandemic strains. Thus, it is indispensable to reconsider the philosophy that involves GAS pathogenesis. The recent investigations involve studying GAS in the nasopharynx and its capability to cause infection or asymptomatically reside in the host. These advances have been discussed in this article with an emphasis on the natural history of GAS and the evolutionary change in the pandemic strains. In addition, this review describes the unique functions for major pathogenicity determinants to comprehend their physiological effects.


Assuntos
Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/genética , Streptococcus pyogenes/patogenicidade , Proteínas de Bactérias/genética , Evolução Molecular , Genoma Bacteriano/genética , Humanos , Infecções Estreptocócicas/patologia , Fatores de Virulência/genética
9.
BMC Infect Dis ; 20(1): 370, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448130

RESUMO

BACKGROUND: Brain abscesses, a severe infectious disease of the CNS, are usually caused by a variety of different pathogens, which include Streptococcus intermedius (S. intermedius). Pulmonary arteriovenous fistulas (PAVFs), characterized by abnormal direct communication between pulmonary artery and vein, are a rare underlying cause of brain abscesses. CASE PRESENTATION: The patient was a previous healthy 55-year-old man who presented with 5 days of headache and fever. Cerebral magnetic resonance imaging (MRI) suggested a brain abscess. Thoracic CT scan and angiography demonstrated PAVFs. Aiding by metagenomic next-generation sequencing (mNGS) of the cerebrospinal fluid (CSF) sample which identified S. intermedius as the causative pathogen, the patient was switched to the single therapy of large dose of penicillin G and was cured precisely and economically. CONCLUSIONS: It is an alternative way to perform mNGS to identify causative pathogens in patients with brain abscesses especially when the results of traditional bacterial culture were negative. Further thoracic CT or pulmonary angiography should also be undertaken to rule out PAVFs as the potential cause of brain abscess if the patient without any known premorbid history.


Assuntos
Fístula Arteriovenosa/diagnóstico por imagem , Abscesso Encefálico/diagnóstico por imagem , Abscesso Encefálico/tratamento farmacológico , Penicilina G/uso terapêutico , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus intermedius/genética , Fístula Arteriovenosa/complicações , Abscesso Encefálico/líquido cefalorraquidiano , Abscesso Encefálico/microbiologia , Angiografia por Tomografia Computadorizada , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/diagnóstico por imagem , Veias Pulmonares/diagnóstico por imagem , Infecções Estreptocócicas/líquido cefalorraquidiano , Infecções Estreptocócicas/microbiologia , Streptococcus intermedius/isolamento & purificação , Resultado do Tratamento
11.
BMC Infect Dis ; 20(1): 351, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32423417

RESUMO

BACKGROUND: Eikenella corrodens and Streptococcus anginosus, which are primary colonization bacteria of the normal flora of the oropharynx, are infrequent bacteria, especially the former. Here, we report a case of lung abscess with a coinfection of Eikenella corrodens and Streptococcus anginosus in a lung cancer patient. CASE PRESENTATION: A 66-year-old Chinese man with lung cancer was admitted to the hospital, complaining of a cough and expectoration for five months and fever for two months. After a series of inspections to differentiate a cancer-related fever from an infectious fever, he was diagnosed with lung abscess. Draining pus culture demonstrated Eikenella corrodens and Streptococcus anginosus. After more than 1 month of antibiotic therapy and draining in total, he gradually recovered to fight against lung cancer. CONCLUSION: This report highlights the increased pathogenicity of Eikenella corrodens and Streptococcus anginosus in an immunocompromised cancer patient, especially after a few invasive operations. Additionally, even though a patient has been diagnosed with cancerous fever, strong vigilance is needed in case an infection arises.


Assuntos
Coinfecção/diagnóstico , Eikenella corrodens/isolamento & purificação , Infecções por Bactérias Gram-Negativas/diagnóstico , Abscesso Pulmonar/microbiologia , Neoplasias Pulmonares/complicações , Infecções Estreptocócicas/diagnóstico , Streptococcus anginosus/isolamento & purificação , Idoso , Antibacterianos/uso terapêutico , Coinfecção/tratamento farmacológico , Drenagem , Febre/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Abscesso Pulmonar/tratamento farmacológico , Masculino , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Resultado do Tratamento
12.
BMC Infect Dis ; 20(1): 302, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321444

RESUMO

BACKGROUND: Estimates of Group B Streptococcus (GBS) disease burden, antimicrobial susceptibility, and serotypes in pregnant women are limited for many resource-limited countries including Kenya. These data are required to inform recommendations for prophylaxis and treatment of infections due to GBS. METHODS: We evaluated the prevalence, antimicrobial susceptibility patterns, serotypes, and risk factors associated with rectovaginal GBS colonization among pregnant women receiving antenatal care at Kenyatta National Hospital (KNH) between August and November 2017. Consenting pregnant women between 12 and 40 weeks of gestation were enrolled. Interview-administered questionnaires were used to assess risk factors associated with GBS colonization. An anorectal swab and a lower vaginal swab were collected and cultured on Granada agar for GBS isolation. Positive colonies were tested for antimicrobial susceptibility to penicillin G, ampicillin, vancomycin, and clindamycin using the disk diffusion method. Serotyping was performed by latex agglutination. Logistic regression was used to identify factors associated with GBS colonization. RESULTS: A total of 292 women were enrolled. Median age was 30 years (Interquartile range {IQR} 26-35) and a median gestational age of 35 weeks (IQR 30-37). Overall GBS was identified in 60/292 (20.5%) of participants. Among the positive isolates, resistance was detected for penicillin G in 42/58 (72.4%) isolates, ampicillin in 32/58 (55.2%) isolates, clindamycin in 14/46 (30.4%) isolates, and vancomycin in 14/58 (24.1%) isolates. All ten GBS serotypes were isolated, and 37/53 (69.8%) of GBS positive participants were colonized by more than one serotype. None of the risk factors was associated with GBS colonization. CONCLUSION: The prevalence of GBS colonization was high among antenatal women at KNH. In addition, a high proportion of GBS isolates were resistant to commonly prescribed intrapartum antibiotics. Hence, other measures like GBS vaccination is a potentially useful approaches to GBS prevention and control in this population. Screening of pregnant mothers for GBS colonization should be introduced and antimicrobial susceptibility test performed on GBS positive samples to guide antibiotic prophylaxis.


Assuntos
Testes de Sensibilidade Microbiana , Complicações Infecciosas na Gravidez/epidemiologia , Reto/microbiologia , Infecções Estreptocócicas/epidemiologia , Streptococcus agalactiae/classificação , Streptococcus agalactiae/isolamento & purificação , Vagina/microbiologia , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Estudos Transversais , Feminino , Humanos , Quênia/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Prevalência , Fatores de Risco , Sorogrupo , Sorotipagem , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/efeitos dos fármacos
13.
PLoS One ; 15(4): e0228122, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32243441

RESUMO

The present study aimed to specify diagnostics for peritonsillar abscesses (PTAs) and to clarify the role of minor salivary glands. This prospective cohort study included 112 patients with acute tonsillitis (AT) and PTA recruited at a tertiary hospital emergency department between February and October 2017. All patients completed a questionnaire concerning their current disease. Serum amylase (S-Amyl) and C-reactive protein (S-CRP) levels, tonsillar findings, and pus aspirate samples and throat cultures were analyzed. Eight of 58 PTA patients (13.8%) had no signs of tonsillar infection. The absence of tonsillar erythema and exudate was associated with low S-CRP (p<0.001) and older age (p<0.001). We also observed an inverse correlation between S-Amyl and S-CRP levels (AT, r = -0.519; PTA, r = -0.353). Therefore, we observed a group of PTA patients without signs of tonsillar infection who had significantly lower S-CRP levels than other PTA patients. These findings support that PTA may be caused by an etiology other than AT. Variations in the S-Amyl levels and a negative correlation between S-Amyl and S-CRP levels may indicate that minor salivary glands are involved in PTA development.


Assuntos
Abscesso Peritonsilar/epidemiologia , Glândulas Salivares Menores/microbiologia , Infecções Estreptocócicas/epidemiologia , Streptococcus pyogenes/isolamento & purificação , Tonsilite/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amilases/sangue , Proteína C-Reativa/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tonsila Palatina/microbiologia , Abscesso Peritonsilar/diagnóstico , Abscesso Peritonsilar/microbiologia , Abscesso Peritonsilar/patologia , Prevalência , Estudos Prospectivos , Glândulas Salivares Menores/patologia , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/patologia , Tonsilite/sangue , Tonsilite/epidemiologia , Tonsilite/microbiologia , Adulto Jovem
14.
Am J Pathol ; 190(4): 862-873, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32200972

RESUMO

Group A streptococcus (GAS) is a major pathogen that impacts health and economic affairs worldwide. Although the oropharynx is the primary site of infection, GAS can colonize the female genital tract and cause severe diseases, such as puerperal sepsis, neonatal infections, and necrotizing myometritis. Our understanding of how GAS genes contribute to interaction with the primate female genital tract is limited by the lack of relevant animal models. Using two genome-wide transposon mutagenesis screens, we identified 69 GAS genes required for colonization of the primate vaginal mucosa in vivo and 96 genes required for infection of the uterine wall ex vivo. We discovered a common set of 39 genes important for GAS fitness in both environments. They include genes encoding transporters, surface proteins, transcriptional regulators, and metabolic pathways. Notably, the genes that encode the surface-exclusion protein (SpyAD) and the immunogenic secreted protein 2 (Isp2) were found to be crucial for GAS fitness in the female primate genital tract. Targeted gene deletion confirmed that isogenic mutant strains ΔspyAD and Δisp2 are significantly impaired in ability to colonize the primate genital tract and cause uterine wall pathologic findings. Our studies identified novel GAS genes that contribute to female reproductive tract interaction that warrant translational research investigation.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Membrana/metabolismo , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/genética , Streptococcus pyogenes/patogenicidade , Doenças Vaginais/microbiologia , Animais , Proteínas de Bactérias/genética , Modelos Animais de Doenças , Feminino , Regulação Bacteriana da Expressão Gênica , Macaca fascicularis , Proteínas de Membrana/genética , Infecções Estreptocócicas/metabolismo , Streptococcus pyogenes/metabolismo , Doenças Vaginais/patologia , Virulência
15.
BMC Infect Dis ; 20(1): 223, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171281

RESUMO

BACKGROUND: Streptococcus suis is a zoonotic pathogen that causes serious systemic infections in pigs and occupation-related infections in humans who contact with pigs or pork products. In China, it has caused two outbreaks of human infection and surveillance for S.suis has been ongoing since last time. CASE PRESENTATION: Two cases of meningitis and sepsis caused by S. suis were reported in this study. Both patients work in relation to the pork trade, a risk factor for S. suis infection. The outcome was favorable after a prolonged ceftriaxone therapy but one patient was left with mild hearing loss. Two isolates were identified as sequencing type (ST) 7, S. suis serotype 2 (SS2), which is one the most prevalent and cause two outbreaks in China. Whole-genome sequencing (WGS) revealed that a high degree identity was noted in the genome organizations and sequences between two sporadic ST7 SS2 isolates in this study and representative epidemic virulent isolates. Major differences among them are two sporadic ST7 SS2 isolates lacked a virulence factor called agglutinin receptor and an 89 K pathogenicity island (PAI), which plays important role in the pathogenesis of streptococcal toxic shock syndrome (STSS). A summary about STs of human infection with S. suis in China was completed. The result showed ST1 and ST7 were still the major STs and several novel STs were successfully discovered in different provinces. CONCLUSIONS: Our results enhanced the understanding of the ability to cause life-threatening infections in humans and the distribution and evolution of the S. suis in China.


Assuntos
Epidemias , Doenças Profissionais/microbiologia , Sorogrupo , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/genética , Streptococcus suis/genética , Doenças dos Suínos/epidemiologia , Idoso , Animais , Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , China/epidemiologia , Genoma Bacteriano/genética , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Choque Séptico/microbiologia , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Streptococcus suis/isolamento & purificação , Suínos/microbiologia , Doenças dos Suínos/transmissão , Resultado do Tratamento , Fatores de Virulência
16.
PLoS One ; 15(3): e0229911, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32155208

RESUMO

BACKGROUND: The unique characteristics of long-term care facilities (LTCFs) including host factors and living conditions contribute to the spread of contagious pathogens. Control measures are essential to interrupt the transmission and to manage outbreaks effectively. AIM: The aim of this systematic review was to verify the causes and problems contributing to transmission and to identify control measures during outbreaks in LTCFs. METHODS: Four electronic databases were searched for articles published from 2007 to 2018. Articles written in English reporting outbreaks in LTCFs were included. The quality of the studies was assessed using the risk-of-bias assessment tool for nonrandomized studies. FINDINGS: A total of 37 studies were included in the qualitative synthesis. The most commonly reported single pathogen was influenza virus, followed by group A streptococcus (GAS). Of the studies that identified the cause, about half of them noted outbreaks transmitted via person-to-person. Suboptimal infection control practice including inadequate decontamination and poor hand hygiene was the most frequently raised issue propagating transmission. Especially, lapses in specific care procedures were linked with outbreaks of GAS and hepatitis B and C viruses. About 60% of the included studies reported affected cases among staff, but only a few studies implemented work restriction during outbreaks. CONCLUSIONS: This review indicates that the violation of basic infection control practice could be a major role in introducing and facilitating the spread of contagious diseases in LTCFs. It shows the need to promote compliance with basic practices of infection control to prevent outbreaks in LTCFs.


Assuntos
Infecção Hospitalar/prevenção & controle , Surtos de Doenças/prevenção & controle , Controle de Infecções/organização & administração , Instituições Residenciais/organização & administração , Infecção Hospitalar/epidemiologia , Higiene das Mãos/organização & administração , Higiene das Mãos/normas , Higiene das Mãos/estatística & dados numéricos , Hepacivirus/isolamento & purificação , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Hepatite B/transmissão , Hepatite B/virologia , Vírus da Hepatite B/isolamento & purificação , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Hepatite C/transmissão , Hepatite C/virologia , Humanos , Higiene/normas , Controle de Infecções/normas , Controle de Infecções/estatística & dados numéricos , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Influenza Humana/transmissão , Influenza Humana/virologia , Assistência de Longa Duração/organização & administração , Assistência de Longa Duração/normas , Assistência de Longa Duração/estatística & dados numéricos , Orthomyxoviridae/isolamento & purificação , Orthomyxoviridae/patogenicidade , Instituições Residenciais/normas , Instituições Residenciais/estatística & dados numéricos , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/prevenção & controle , Infecções Estreptocócicas/transmissão , Streptococcus pyogenes/isolamento & purificação
17.
J Med Microbiol ; 69(4): 576-586, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32125264

RESUMO

Introduction. In some species, the population structure of pathogenic bacteria is clonal. However, the mechanisms that determine the predominance and persistence of specific bacterial lineages of group C Streptococcus remain poorly understood. In Brazil, a previous study revealed the predominance of two main lineages of Streptococcus dysgalactiae subsp. equisimilis (SDSE).Aim. The aim of this study was to assess the virulence and fitness advantages that might explain the predominance of these SDSE lineages for a long period of time.Methodology. emm typing was determined by DNA sequencing. Adhesion and invasion tests were performed using human bronchial epithelial cells (16HBE14o-). Biofilm formation was tested on glass surfaces and the presence of virulence genes was assessed by PCR. Additionally, virulence was studied using Caenorhabditis elegans models and competitive fitness was analysed in murine models.Results. The predominant lineages A and B were mostly typed as emm stC839 and stC6979, respectively. Notably, these lineages exhibited a superior ability to adhere and invade airway cells. Furthermore, the dominant lineages were more prone to induce aversive olfactory learning and more likely to kill C. elegans. In the competitive fitness assays, they also showed increased adaptability. Consistent with the increased virulence observed in the ex vivo and in vivo models, the predominant lineages A and B showed a higher number of virulence-associated genes and a superior ability to accumulate biofilm.Conclusion. These results suggest strongly that this predominance did not occur randomly but rather was due to adaptive mechanisms that culminated in increased colonization and other bacterial properties that might confer increased bacteria-host adaptability to cause disease.


Assuntos
Biodiversidade , Infecções Estreptocócicas/microbiologia , Streptococcus/patogenicidade , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Brasil , Caenorhabditis elegans , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Streptococcus/classificação , Streptococcus/genética , Streptococcus/isolamento & purificação , Virulência
18.
PLoS One ; 15(3): e0229064, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32214338

RESUMO

Streptococcus pyogenes is a strict human pathogen responsible for more than 700 million infections annually worldwide. Strains of serotype M28 S. pyogenes are typically among the five more abundant types causing invasive infections and pharyngitis in adults and children. Type M28 strains also have an unusual propensity to cause puerperal sepsis and neonatal disease. We recently discovered that a one-nucleotide indel in an intergenic homopolymeric tract located between genes Spy1336/R28 and Spy1337 altered virulence in a mouse model of infection. In the present study, we analyzed size variation in this homopolymeric tract and determined the extent of heterogeneity in the number of tandemly-repeated 79-amino acid domains in the coding region of Spy1336/R28 in large samples of strains recovered from humans with invasive infections. Both repeat sequence elements are highly polymorphic in natural populations of M28 strains. Variation in the homopolymeric tract results in (i) changes in transcript levels of Spy1336/R28 and Spy1337 in vitro, (ii) differences in virulence in a mouse model of necrotizing myositis, and (iii) global transcriptome changes as shown by RNAseq analysis of isogenic mutant strains. Variation in the number of tandem repeats in the coding sequence of Spy1336/R28 is responsible for size variation of R28 protein in natural populations. Isogenic mutant strains in which genes encoding R28 or transcriptional regulator Spy1337 are inactivated are significantly less virulent in a nonhuman primate model of necrotizing myositis. Our findings provide impetus for additional studies addressing the role of R28 and Spy1337 variation in pathogen-host interactions.


Assuntos
Proteínas de Bactérias/genética , Fasciite Necrosante/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/genética , Streptococcus pyogenes/isolamento & purificação , Virulência/genética , Animais , Modelos Animais de Doenças , Fasciite Necrosante/patologia , Regulação Bacteriana da Expressão Gênica , Heterogeneidade Genética , Humanos , Camundongos , Polimorfismo Genético , Infecções Estreptocócicas/patologia , Transcriptoma , Fatores de Virulência/genética
19.
Nat Commun ; 11(1): 1502, 2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32198389

RESUMO

Although certain microbial lipids are toxins, the structural features important for cytotoxicity remain unknown. Increased functional understanding is essential for developing therapeutics against toxic microbial lipids. Group B Streptococci (GBS) are bacteria associated with preterm births, stillbirths, and severe infections in neonates and adults. GBS produce a pigmented, cytotoxic lipid, known as granadaene. Despite its importance to all manifestations of GBS disease, studies towards understanding granadaene's toxic activity are hindered by its instability and insolubility in purified form. Here, we report the synthesis and screening of lipid derivatives inspired by granadaene, which reveal features central to toxin function, namely the polyene chain length. Furthermore, we show that vaccination with a non-toxic synthetic analog confers the production of antibodies that inhibit granadaene-mediated hemolysis ex vivo and diminish GBS infection in vivo. This work provides unique structural and functional insight into granadaene and a strategy to mitigate GBS infection, which will be relevant to other toxic lipids encoded by human pathogens.


Assuntos
Hemólise , Lipídeos/química , Polienos/química , Nascimento Prematuro/microbiologia , Infecções Estreptocócicas/metabolismo , Adulto , Animais , Linfócitos B , Toxinas Bacterianas/química , Vacinas Bacterianas , Linfócitos T CD4-Positivos , Modelos Animais de Doenças , Feminino , Humanos , Recém-Nascido , Lipídeos/imunologia , Lipídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Polienos/imunologia , Gravidez , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/prevenção & controle , Streptococcus agalactiae , Vacinação
20.
Res Vet Sci ; 130: 68-72, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32146377

RESUMO

Modified-live virus (MLV) vaccines derived from highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) were wildly used in China, which resulted in the emergence of MLV-like strains in pigs. Previous studies demonstrated that secondary bacterial infection could enhance HP-PRRSV infection-mediated inflammatory responses, but it is unknown whether early bacterial infection could enhance the HP-PRRSV MLV-like infection-mediated pathological reaction. In this paper, to gain the evidence for infection of pigs with MLV-like strains in China, we firstly analyzed the genetic characterization of the HP-PRRSV MLV-like isolate (TJxq1701) and further evaluated whether the early Streptococcus suis infection synergizes HP-PRRSV MLV-like infection-mediated pathological reaction. Our results showed that the whole genome of TJxq1701 shared the highest homology with JXA1-P80 and a total of 16 amino acids residues unique to JXA1-P80 in ORF1a, ORF1b, GP2, GP3, GP4, and GP5 were found in the corresponding locations. The results of infection experiments in pigs revealed that TJxq1701 caused transitional fever, moderate respiratory clinical sign and microscopic lung lesions in piglets, but early infection with low virulence Streptococcus suis serotype 2 (SS2) exhibited seriously clinical signs, including high fever, anorexia, and respiratory distress, leading to 60% mortality within four weeks in comparison with alone infected group. Taken together, our findings reveal that early bacterial infection could enhance the HP-PRRSV MLV-like infection-mediated pathological reaction, which provide an important clue for understanding that streptococcus infection increases the pathogenicity of MLV-like virus and a new thought for prevention and control of PRRSV.


Assuntos
Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/patogenicidade , Infecções Estreptocócicas/veterinária , Streptococcus suis/fisiologia , Doenças dos Suínos/virologia , Animais , Sorogrupo , Infecções Estreptocócicas/microbiologia , Streptococcus suis/genética , Suínos , Doenças dos Suínos/microbiologia , Vacinas Atenuadas , Virulência
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