RESUMO
AIMS: To evaluate the prevalence, molecular characteristics, antimicrobial susceptibility, and epithelial invasion of Streptococcus agalactiae strains isolated from pregnant women and newborns in Rio de Janeiro, Brazil. METHODS AND RESULTS: A total of 67 S. agalactiae isolates, 48 isolates from pregnant women and 19 from neonates, were analyzed. Capsular type Ia and V were predominant (35.8%/each). The multilocus sequence typing analysis revealed the presence of 19 STs grouped into 6 clonal complexes with prevalence of CC17/40.3% and CC23/34.3%. The lmb and iag virulence genes were found in 100% of isolates. Four S. agalactiae strains, belonging to CC17/ST1249 and CC23/ST23, were able to adhere to A549 respiratory epithelial cells. Antimicrobial resistance was verified mainly to tetracycline (85%), erythromycin (70.8%), and clindamycin (58.3%). Four S. agalactiae isolates were multidrug resistant. The resistance genes tested were found in 92.5% of isolates for tetM, 58.2% for ermB, 28.4% for mefAE, and 10.4% for tetO. CONCLUSION: The study showed a high prevalence of virulence and antimicrobial genes in S. agalactiae strains isolated from pregnant women and newborns, supporting the idea that continued surveillance is necessary to identify risk factors and perform long-term follow-up in pregnant women and neonates in Rio de Janeiro.
Assuntos
Antibacterianos , Células Epiteliais , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Infecções Estreptocócicas , Streptococcus agalactiae , Streptococcus agalactiae/genética , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/isolamento & purificação , Feminino , Humanos , Brasil , Gravidez , Infecções Estreptocócicas/microbiologia , Antibacterianos/farmacologia , Recém-Nascido , Células Epiteliais/microbiologia , Farmacorresistência Bacteriana/genética , Adulto , Fatores de Virulência/genética , Complicações Infecciosas na Gravidez/microbiologia , Farmacorresistência Bacteriana Múltipla/genética , Virulência/genéticaRESUMO
BACKGROUND: Streptococcus agalactiae capsular type III strains are a leading cause of invasive neonatal infections. Many pathogens have developed mechanisms to escape from host defense response using the host membrane microdomain machinery. Lipid rafts play an important role in a variety of cellular functions and the benefit provided by interaction with lipid rafts can vary from one pathogen to another. OBJECTIVES: This study aims to evaluate the involvement of membrane microdomains during infection of human endothelial cell by S. agalactiae. METHODS: The effects of cholesterol depletion and PI3K/AKT signaling pathway activation during S. agalactiae-human umbilical vein endothelial cells (HUVEC) interaction were analysed by pre-treatment with methyl-ß-cyclodextrin (MßCD) or LY294002 inhibitors, immunofluorescence and immunoblot analysis. The involvement of lipid rafts was analysed by colocalisation of bacteria with flotillin-1 and caveolin-1 using fluorescence confocal microscopy. FINDINGS: In this work, we demonstrated the importance of the integrity of lipid rafts microdomains and activation of PI3K/Akt pathway during invasion of S. agalactiae strain to HUVEC cells. Our results suggest the involvement of flotillin-1 and caveolin-1 during the invasion of S. agalactiae strain in HUVEC cells. CONCLUSIONS: The collection of our results suggests that lipid microdomain affects the interaction of S. agalactiae type III belonging to the hypervirulent ST-17 with HUVEC cells through PI3K/Akt signaling pathway.
Assuntos
Células Endoteliais/virologia , Lipídeos de Membrana , Microdomínios da Membrana/virologia , Streptococcus agalactiae/patogenicidade , Virulência , Humanos , Recém-Nascido , Streptococcus agalactiae/genéticaRESUMO
A maternal vaccine to protect newborns against invasive Streptococcus agalactiae infection is a developing medical need. The vaccine should be offered during the third trimester of pregnancy and induce strong immune responses and placental transfer of protective antibodies. Polysaccharide vaccines against S. agalactiae conjugated to protein carriers are in advanced stages of development. Additionally, protein-based vaccines are also in development, showing great promise as they can provide protection regardless of serotype. Furthermore, safety concerns regarding a new vaccine are the main barriers identified. Here, we present vaccines in development and identified safety, cost, and efficacy concerns, especially in high-need, low-income countries.
Assuntos
Infecções Estreptocócicas , Vacinas Estreptocócicas , Streptococcus agalactiae , Streptococcus agalactiae/imunologia , Humanos , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/prevenção & controle , Infecções Estreptocócicas/microbiologia , Vacinas Estreptocócicas/imunologia , Gravidez , Feminino , Animais , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/microbiologia , Desenvolvimento de Vacinas , Recém-Nascido , Anticorpos Antibacterianos/imunologiaRESUMO
Sepsis is a generalized disease characterized by an extreme response to a severe infection. Moreover, challenges remain in the diagnosis, treatment and management of septic patients. In this mini-review we demonstrate developments on cellular pathogenesis and the role of Caveolin-1 (Cav-1) in sepsis. Studies have shown that Cav-1 has a significant role in sepsis through the regulation of membrane traffic and intracellular signaling pathways. In addition, activation of apoptosis/autophagy is considered relevant for the progression and development of sepsis. However, how Cav-1 is involved in sepsis remains unclear, and the precise mechanisms need to be further investigated. Finally, the role of Cav-1 in altering cell permeability during inflammation, in sepsis caused by microorganisms, apoptosis/autophagy activation and new therapies under study are discussed in this mini-review.
Assuntos
Caveolina 1 , Sepse , Autofagia/fisiologia , Caveolina 1/genética , Caveolina 1/metabolismo , Humanos , Permeabilidade , Sepse/genética , Sepse/metabolismo , Transdução de SinaisRESUMO
Streptococcus agalactiae is a recognized pathogen associated with infections in neonates, elderly, and immunocompromised adults, particularly those with cancer. In the present investigation, clinical-epidemiological features, multidrug resistance profiles, and virulence genes of S. agalactiae strains isolated from cancer patients were investigated. S. agalactiae capsular distribution assays demonstrated that Ia (43.6%) and V (23.6%) types were predominantly detected among 55 clinical isolates tested; only one strain (GBS1428) was capsular type III/ST-17. The fbsB and hylB genes were detected in all isolates, while the iag, lmb, and fbsA genes were detected in 94.5%, 91%, and 91% of oncological isolates, respectively. The combination of PI-1 and PI-2a was the most common (60%) among S. agalactiae strains isolated from oncologic patients. S. agalactiae strains were resistant to tetracycline (85.5%), erythromycin (9%), and clindamycin (5.5%). Norfloxacin non-susceptible was detected in 7.3% of S. agalactiae strains. Our findings reinforce the need for S. agalactiae control measures in Brazil, including cancer patients.
Assuntos
Neoplasias/complicações , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/genética , Streptococcus agalactiae/isolamento & purificação , Adolescente , Adulto , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Brasil/epidemiologia , Farmacorresistência Bacteriana Múltipla , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Neoplasias/microbiologia , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/patogenicidade , Fatores de Virulência/genética , Adulto JovemRESUMO
Streptococcus agalactiae are important pathogenic bacteria that cause severe infections in humans, especially neonates. The mechanism by which ST-17 causes invasive infections than other STs is not well understood. In this study, we sequenced the first genome of a S. agalactiae ST-17 strain isolated in Brazil using the Illumina HiSeq 2500 technology. S. agalactiae GBS90356 ST-17 belongs to the capsular type III and was isolated from a neonatal with a fatal case of meningitis. The genome presented a size of 2.03 Mbp and a Gâ¯+â¯C content of 35.2%. S. agalactiae has 706 genes in its core genome and an open pan-genome with a size of 5.020 genes, suggesting a high genomic plasticity. GIPSy software was used to identify 10 Pathogenicity islands (PAIs) which corresponded to 15% of the genome size. IslandViewer4 corroborated the prediction of six PAIs. The pathogenicity islands showed important virulence factors genes for S. agalactiae e.g. neu, cps, dlt, fbs, cfb, lmb. SignalP detected 20 proteins with signal peptides among the 352 proteins found in PAIs, which 60% were located in the SagPAI_5. SagPAI_2 and 5 were mainly detected in ST-17 strains studied. Moreover, we identified 51 unique genes, 9 recombination regions and a large number of SNPs with an average of 760.3 polymorphisms, which can be related with high genomic plasticity and virulence during host-pathogen interactions. Our results showed implications for pathogenesis, evolution, concept of species and in silico analysis value to understand the epidemiology and genome plasticity of S. agalactiae.