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1.
BMC Infect Dis ; 20(1): 621, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32831057

RESUMO

BACKGROUND: We aimed to describe an outbreak of cutaneous abscesses caused by Panton-Valentine leukocidin (PVL)-producing methicillin-susceptible Staphylococcus aureus (MSSA) among gold mine workers. METHODS: In February 2018, we retrospectively reviewed a random sample of 50 medical records from 243 cases and conducted face-to-face interviews using a structured questionnaire. Pus aspirates were sent to the National Institute for Communicable Diseases from prospectively-identified cases (November 2017-March 2018). Nasopharyngeal swabs were collected during a colonisation survey in February 2018. Staphylococcus aureus isolates were screened with a conventional PCR for lukS/F-PV. Pulsed-field gel electrophoresis (PFGE) was performed to determine the genetic relatedness among the isolates. A sample of isolates were selected for whole genome sequencing (WGS). We conducted an assessment on biological risks associated with mining activities. RESULTS: From January 2017 to February 2018, 10% (350/3582) of mine workers sought care for cutaneous abscesses. Forty-seven medical files were available for review, 96% were male (n = 45) with a mean age of 43 years (SD = 7). About 52% (24/46) were involved in stoping and 28% (13/47) worked on a particular level. We cultured S. aureus from 79% (30/38) of cases with a submitted specimen and 14% (12/83) from colonisation swabs. All isolates were susceptible to cloxacillin. Seventy-one percent of S. aureus isolates (30/42) were PVL-PCR-positive. Six PFGE clusters were identified, 57% (21/37) were closely related. WGS analysis found nine different sequence types. PFGE and WGS analysis showed more than one cluster of S. aureus infections involving closely related isolates. Test reports for feed and product water of the mine showed that total plate counts were above the limits of 1000 cfu/ml, coliform counts > 10 cfu/100 ml and presence of faecal coliforms. Best practices were poorly implemented as some mine workers washed protective clothing with untreated water and hung them for drying at the underground surface. CONCLUSIONS: PVL-producing MSSA caused an outbreak of cutaneous abscesses among underground workers at a gold mining company. To our knowledge, no other outbreaks of PVL-producing S. aureus involving skin and soft tissue infections have been reported in mining facilities in South Africa. We recommend that worker awareness of infection prevention and control practices be strengthened.


Assuntos
Abscesso/microbiologia , Dermatopatias/epidemiologia , Infecções dos Tecidos Moles/epidemiologia , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/patogenicidade , Adulto , Toxinas Bacterianas/metabolismo , Surtos de Doenças , Eletroforese em Gel de Campo Pulsado , Exotoxinas/metabolismo , Feminino , Ouro , Humanos , Leucocidinas/metabolismo , Masculino , Meticilina/farmacologia , Pessoa de Meia-Idade , Mineradores , Estudos Retrospectivos , Dermatopatias/microbiologia , Infecções dos Tecidos Moles/microbiologia , África do Sul/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo
2.
BMC Infect Dis ; 20(1): 602, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32799799

RESUMO

BACKGROUND: The objectives of this study were to determine for the first time, in Morocco, the nasal carriage rate, antimicrobial susceptibility profiles and virulence genes of Staphylococcus. aureus isolated from animals and breeders in close contact. METHODS: From 2015 to 2016, 421 nasal swab samples were collected from 26 different livestock areas in Tangier. Antimicrobial susceptibility phenotypes were determined by disk diffusion according to EUCAST 2015. The presence of nuc, mecA, mecC, lukS/F-PV, and tst genes were determined by Polymerase Chain Reaction (PCR) for all isolates. RESULTS: The overall S. aureus nasal carriage rate was low in animals (9.97%) and high in breeders (60%) with a statistically significant difference, (OR = 13.536; 95% CI = 7.070-25.912; p < 0.001). In general, S. aureus strains were susceptible to the majority of antibiotics and the highest resistance rates were found against tetracycline (16.7% in animals and 10% in breeders). No Methicillin-Resistant S. aureus (MRSA) was detected in animals and breeders. A high rate of tst and lukS/F-PV genes has been recovered only from animals (11.9 and 16.7%, respectively). CONCLUSION: Despite the lower rate of nasal carriage of S. aureus and the absence of MRSA strains in our study, S. aureus strains harbored a higher frequency of tst and lukS/F-PV virulence genes, which is associated to an increased risk of infection dissemination in humans. This highlights the need for further larger and multi-center studies to better define the transmission of the pathogenic S. aureus between livestock, environment, and humans.


Assuntos
Nariz/microbiologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/veterinária , Staphylococcus aureus/efeitos dos fármacos , Animais , Animais Domésticos/microbiologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Portador Sadio , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Humanos , Leucocidinas/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Nuclease do Micrococo/genética , Marrocos/epidemiologia , Proteínas de Ligação às Penicilinas/genética , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/patogenicidade , Tetraciclina/farmacologia , Virulência/genética
3.
Nucleic Acids Res ; 48(15): 8545-8561, 2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32735661

RESUMO

A crucial bacterial strategy to avoid killing by antibiotics is to enter a growth arrested state, yet the molecular mechanisms behind this process remain elusive. The conditional overexpression of mazF, the endoribonuclease toxin of the MazEF toxin-antitoxin system in Staphylococcus aureus, is one approach to induce bacterial growth arrest, but its targets remain largely unknown. We used overexpression of mazF and high-throughput sequence analysis following the exact mapping of non-phosphorylated transcriptome ends (nEMOTE) technique to reveal in vivo toxin cleavage sites on a global scale. We obtained a catalogue of MazF cleavage sites and unearthed an extended MazF cleavage specificity that goes beyond the previously reported one. We correlated transcript cleavage and abundance in a global transcriptomic profiling during mazF overexpression. We observed that MazF affects RNA molecules involved in ribosome biogenesis, cell wall synthesis, cell division and RNA turnover and thus deliver a plausible explanation for how mazF overexpression induces stasis. We hypothesize that autoregulation of MazF occurs by directly modulating the MazEF operon, such as the rsbUVW genes that regulate the sigma factor SigB, including an observed cleavage site on the MazF mRNA that would ultimately play a role in entry and exit from bacterial stasis.


Assuntos
Proteínas de Ligação a DNA/genética , Endorribonucleases/genética , Proteínas de Escherichia coli/genética , Staphylococcus aureus/genética , Sistemas Toxina-Antitoxina/genética , Antibacterianos/farmacologia , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA/química , Escherichia coli/genética , Humanos , Óperon/genética , RNA Mensageiro/genética , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Especificidade por Substrato , Transcriptoma/genética
4.
PLoS Genet ; 16(7): e1008779, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32730248

RESUMO

Staphylococcus aureus is an opportunistic pathogen that can grow in a wide array of conditions: on abiotic surfaces, on the skin, in the nose, in planktonic or biofilm forms and can cause many type of infections. Consequently, S. aureus must be able to adapt rapidly to these changing growth conditions, an ability largely driven at the posttranscriptional level. RNA helicases of the DEAD-box family play an important part in this process. In particular, CshA, which is part of the degradosome, is required for the rapid turnover of certain mRNAs and its deletion results in cold-sensitivity. To understand the molecular basis of this phenotype, we conducted a large genetic screen isolating 82 independent suppressors of cold growth. Full genome sequencing revealed the fatty acid synthesis pathway affected in many suppressor strains. Consistent with that result, sublethal doses of triclosan, a FASII inhibitor, can partially restore growth of a cshA mutant in the cold. Overexpression of the genes involved in branched-chain fatty acid synthesis was also able to suppress the cold-sensitivity. Using gas chromatography analysis of fatty acids, we observed an imbalance of straight and branched-chain fatty acids in the cshA mutant, compared to the wild-type. This imbalance is compensated in the suppressor strains. Thus, we reveal for the first time that the cold sensitive growth phenotype of a DEAD-box mutant can be explained, at least partially, by an improper membrane composition. The defect correlates with an accumulation of the pyruvate dehydrogenase complex mRNA, which is inefficiently degraded in absence of CshA. We propose that the resulting accumulation of acetyl-CoA fuels straight-chained fatty acid production at the expense of the branched ones. Strikingly, addition of acetate into the medium mimics the cshA deletion phenotype, resulting in cold sensitivity suppressed by the mutations found in our genetic screen or by sublethal doses of triclosan.


Assuntos
RNA Helicases DEAD-box/genética , Ácidos Graxos/metabolismo , Infecções Estafilocócicas/genética , Staphylococcus aureus/genética , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Ácidos Graxos/genética , Regulação Bacteriana da Expressão Gênica/genética , Humanos , Proteínas de Membrana/genética , RNA Mensageiro/genética , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/patogenicidade
5.
Nat Commun ; 11(1): 3526, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32665571

RESUMO

Gene tandem amplifications are thought to drive bacterial evolution, but they are transient in the absence of selection, making their investigation challenging. Here, we analyze genomic sequences of Staphylococcus aureus USA300 isolates from the same geographical area to identify variations in gene copy number, which we confirm by long-read sequencing. We find several hotspots of variation, including the csa1 cluster encoding lipoproteins known to be immunogenic. We also show that the csa1 locus expands and contracts during bacterial growth in vitro and during systemic infection of mice, and recombination creates rapid heterogeneity in initially clonal cultures. Furthermore, csa1 copy number variants differ in their immunostimulatory capacity, revealing a mechanism by which gene copy number variation can modulate the host immune response.


Assuntos
Genoma Bacteriano/genética , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Animais , Evolução Biológica , Genótipo , Camundongos , Fenótipo , Staphylococcus aureus/patogenicidade
6.
PLoS One ; 15(7): e0236319, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726328

RESUMO

Jacaranda mimosifolia trees are grown in frost-free regions globally. The aim of this study was to evaluate the methanol crude extract and various fractions of increasing polarity of J. mimosifolia leaves for bioactive metabolites, as well as antimicrobial, antioxidant and anticancer activities. The anti-inflammatory potential of the various fractions of J. mimosifolia leaf extract was studied via the lipoxygenase (LOX) inhibitory assay. Methanol crude extract (ME), derived fractions extracted with chloroform (CF) and ethyl acetate (EAF), and residual aqueous extract (AE) of dried J. mimosifolia leaves were assayed for polyphenolic compounds, their antioxidant, antimicrobial and lipoxygenase (LOX) inhibitory activities, and anticancer properties. Polyphenolic compounds were determined via HPLC while phytochemicals (total phenolics, flavonoids, tannins and ortho-diphenol contents), antioxidant activities (DPPH, hydrogen peroxideperoxide, hydroxyl and superoxide radical anions) and LOX were measured via spectrophotometry. Methanol extracts and various fractions were evaluated for antibacterial activities against Bacillus subtilis, Klebsiella pneumonia, Pseudomonas aeruginosa and Staphylococcus aureus. Antifungal potential of the fractions was tested against three species: Aspergillus flavus, Aspergillus fumigatus and Fusarium oxysporum. The highest values for total phenolic content (TPC), total flavonoid content (TFC), flavonols, tannins and ortho-diphenols were in the ME, followed by CF > EAF > AE. ME also had the highest antioxidant activity with EC50 values 48±1.3, 45±2.4, 42±1.3 and 46±1.3 µg/mL based on the DPPH, hydrogen peroxide, hydroxyl radical and superoxide radical assays, respectively. TPC and TFC showed a significant, strong and positive correlation with the values for each of these antioxidant activities. ME exhibited anti-inflammatory potential based on its LOX inhibitory activity (IC50 = 1.3 µg/mL). ME also had the maximum antibacterial and antifungal potential, followed by EAF > CF > AE. Furthermore, ME showed the strongest cytotoxic effect (EC50 = 10.7 and 17.3 µg/mL) against human hormone-dependent prostate carcinoma (LnCaP) and human lung carcinoma (LU-1) cell lines, respectively. Bioactive compounds present in leaf methanol extracts of J. mimosifolia were identified using gas chromatography-mass spectrometry (GC-MS). Fifteen compounds were identified including phenolic and alcoholic compounds, as well as fatty acids. Our results suggest that J. mimosifolia leaves are a good source of natural products with antioxidant, anti-inflammatory and anti-cancer properties for potential therapeutic, nutraceutical and functional food applications.


Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Bignoniaceae/química , Extratos Vegetais/farmacologia , Anti-Infecciosos/química , Antioxidantes/química , Aspergillus/efeitos dos fármacos , Aspergillus/patogenicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citotoxinas/química , Citotoxinas/farmacologia , Humanos , Inibidores de Lipoxigenase/química , Inibidores de Lipoxigenase/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Extratos Vegetais/química , Folhas de Planta/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade
7.
PLoS One ; 15(6): e0234542, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555702

RESUMO

Staphylococcus aureus is one of the principal causative agents of bacteremia which can progress to sepsis. Rapid diagnostic tests for identification and antibiotic resistance profiling of S. aureus would improve patient outcomes and antibiotic stewardship, but existing methods require a lengthy culture step to obtain enough material for testing. Complexity of the host matrix, where pathogenic microbes are often present, also interferes with many diagnostic methods. Here, we describe a straightforward and rapid method for enriching viable S. aureus using bio-orthogonal, or "click," chemistry methods. Bacteria labeled in this manner can potentially be cultured, interrogated using molecular methods for pathogen identification, or used to test antibiotic susceptibility.


Assuntos
Técnicas Bacteriológicas , Sepse/diagnóstico , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus/isolamento & purificação , Testes Diagnósticos de Rotina , Farmacorresistência Bacteriana , Humanos , Sepse/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/patogenicidade , Propriedades de Superfície
8.
Medicine (Baltimore) ; 99(26): e20892, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590796

RESUMO

INTRODUCTION: Patients with rheumatoid arthritis (RA) tend to be immunosuppressed due to RA itself and the therapeutic drugs administered. The management of surgical site infection (SSI) following upper cervical spinal instrumented fusion in RA patients is challenging; however, literature on the treatment for such conditions is scarce. We report 3 consecutive patients with RA, who developed deep SSI following upper cervical posterior fusion and were treated using antibiotic-loaded bone cement (ALBC). PATIENT CONCERNS: All 3 patients reported in the current study experienced compression myelopathy with upper cervical spinal deformity and received prednisolone and methotrexate for controlling RA preoperatively. The patient in Case 1 underwent C1-2 posterior fusion and developed deep SSI due to methicillin-sensitive Staphylococcus aureus at 3 months postoperatively; the patient in Case 2 underwent occipito-C2 posterior fusion and developed deep SSI due to methicillin-sensitive Staphylococcus aureus at 2 weeks postoperatively; and the patient in Case 3 underwent occipito-C2 posterior instrumented fusion and laminoplasty at C3-7, and developed deep SSI due to methicillin-resistant coagulase negative staphylococci at 3 weeks postoperatively. DIAGNOSIS: All patients developed deep staphylococcal SSI in the postoperative period. INTERVENTIONS: All 3 patients were treated using ALBC placed on and around the instrumentation to cover them and occupy the dead space after radical open debridement. OUTCOMES: The deep infection was resolved uneventfully after the single surgical intervention retaining spinal instrumentation. Good clinical outcomes of the initial surgery were maintained until the final follow-up without recurrence of SSI in all 3 cases. CONCLUSION: ALBC embedding spinal instrumentation procedure can be a viable treatment for curing SSI in complex cases, such as patients with RA who undergo high cervical fusion surgeries without implant removal.


Assuntos
Artrite Reumatoide/complicações , Cimentos para Ossos/uso terapêutico , Luxações Articulares/cirurgia , Infecções Estafilocócicas/tratamento farmacológico , Adulto , Idoso , Antibacterianos/uso terapêutico , Artrite Reumatoide/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Fusão Vertebral/efeitos adversos , Infecções Estafilocócicas/etiologia , Infecções Estafilocócicas/fisiopatologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/cirurgia
9.
J Infect Public Health ; 13(9): 1360-1362, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32507402

RESUMO

A pre-school aged boy presented to the Pediatric Emergency Department with a high grade fever and neck pain and stiffness. Blood culture was positive for methicillin-sensitive Staphylococcus aureus (MSSA) and Doppler ultrasound of the neck revealed partial thrombosis of the left internal jugular vein. He was diagnosed with Lemierre's syndrome (LS) and treated with a prolonged course of antibiotics and anticoagulation. After discharge home, he was followed in the outpatient clinics and had a full recovery. This case report will highlight the presentation of LS and will briefly review the microbiology of this condition.


Assuntos
Síndrome de Lemierre/diagnóstico , Síndrome de Lemierre/microbiologia , Staphylococcus aureus/patogenicidade , Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Pré-Escolar , Humanos , Veias Jugulares/diagnóstico por imagem , Síndrome de Lemierre/tratamento farmacológico , Masculino , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Resultado do Tratamento , Ultrassonografia
10.
PLoS One ; 15(5): e0232987, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407399

RESUMO

Escherichia coli and Staphylococcus aureus are important agents of urinary tract infections that can often evolve to severe infections. The rise of antibiotic-resistant strains has driven the search for novel therapies to replace the use or act as adjuvants of antibiotics. In this context, plant-derived compounds have been widely investigated. Cuminaldehyde is suggested as the major antimicrobial compound of the cumin seed essential oil. However, this effect is not fully understood. Herein, we investigated the in silico and in vitro activities of cuminaldehyde, as well as its ability to potentiate ciprofloxacin effects against S. aureus and E. coli. In silico analyses were performed by using different computational tools. The PASS online and SwissADME programmes were used for the prediction of biological activities and oral bioavailability of cuminaldehyde. For analysis of the possible toxic effects and the theoretical pharmacokinetic parameters of the compound, the Osiris, SwissADME and PROTOX programmes were used. Estimations of cuminaldehyde gastrointestinal absorption, blood brain barrier permeability and skin permeation by using SwissADME; and drug likeness and score by using Osiris, were also evaluated The in vitro antimicrobial effects of cuminaldehyde were determined by using microdilution, biofilm formation and time-kill assays. In silico analysis indicated that cuminaldehyde may act as an antimicrobial and as a membrane permeability enhancer. It was suggested to be highly absorbable by the gastrointestinal tract and likely to cross the blood brain barrier. Also, irritative and harmful effects were predicted for cuminaldehyde if swallowed at its LD50. Good oral bioavailability and drug score were also found for this compound. Cuminaldehyde presented antimicrobial and anti-biofilm effects against S. aureus and E. coli.. When co-incubated with ciprofloxacin, it enhanced the antibiotic antimicrobial and anti-biofilm actions. We suggest that cuminaldehyde may be useful as an adjuvant therapy to ciprofloxacin in S. aureus and E. coli-induced infections.


Assuntos
Antibacterianos/administração & dosagem , Benzaldeídos/administração & dosagem , Ciprofloxacino/administração & dosagem , Cimenos/administração & dosagem , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Adjuvantes Farmacêuticos/administração & dosagem , Adjuvantes Farmacêuticos/farmacocinética , Adjuvantes Farmacêuticos/toxicidade , Administração Oral , Benzaldeídos/farmacocinética , Benzaldeídos/toxicidade , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Disponibilidade Biológica , Simulação por Computador , Cimenos/farmacocinética , Cimenos/toxicidade , Sinergismo Farmacológico , Escherichia coli/patogenicidade , Escherichia coli/fisiologia , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Técnicas In Vitro , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/patogenicidade , Staphylococcus aureus/fisiologia , Infecções Urinárias/tratamento farmacológico
11.
Proc Natl Acad Sci U S A ; 117(20): 10989-10999, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32354997

RESUMO

Staphylococcus aureus infections can lead to diseases that range from localized skin abscess to life-threatening toxic shock syndrome. The SrrAB two-component system (TCS) is a global regulator of S. aureus virulence and critical for survival under environmental conditions such as hypoxic, oxidative, and nitrosative stress found at sites of infection. Despite the critical role of SrrAB in S. aureus pathogenicity, the mechanism by which the SrrAB TCS senses and responds to these environmental signals remains unknown. Bioinformatics analysis showed that the SrrB histidine kinase contains several domains, including an extracellular Cache domain and a cytoplasmic HAMP-PAS-DHp-CA region. Here, we show that the PAS domain regulates both kinase and phosphatase enzyme activity of SrrB and present the structure of the DHp-CA catalytic core. Importantly, this structure shows a unique intramolecular cysteine disulfide bond in the ATP-binding domain that significantly affects autophosphorylation kinetics. In vitro data show that the redox state of the disulfide bond affects S. aureus biofilm formation and toxic shock syndrome toxin-1 production. Moreover, with the use of the rabbit infective endocarditis model, we demonstrate that the disulfide bond is a critical regulatory element of SrrB function during S. aureus infection. Our data support a model whereby the disulfide bond and PAS domain of SrrB sense and respond to the cellular redox environment to regulate S. aureus survival and pathogenesis.


Assuntos
Proteínas de Bactérias/metabolismo , Cisteína/metabolismo , Proteínas Repressoras/metabolismo , Staphylococcus aureus/metabolismo , Animais , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Toxinas Bacterianas , Sequência de Bases , Biofilmes , Domínio Catalítico , Modelos Animais de Doenças , Endocardite , Enterotoxinas , Feminino , Regulação Bacteriana da Expressão Gênica , Histidina Quinase/metabolismo , Masculino , Modelos Moleculares , Mutação , Oxirredução , Domínios Proteicos , Coelhos , Proteínas Repressoras/química , Proteínas Repressoras/genética , Sepse , Infecções Estafilocócicas/metabolismo , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Superantígenos , Thermotoga maritima , Virulência/genética , Virulência/fisiologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-32235764

RESUMO

Staphylococcus aureus is an important bacterial pathogen. This study utilized known staphylococcal epidemiology to track S. aureus between patients, surfaces, staff hands and air in a ten-bed intensive care unit (ICU). METHODS: Patients, air and surfaces were screened for total colony counts and S. aureus using dipslides, settle plates and an MAS-100 slit-sampler once a month for 10 months. Data were modelled against proposed standards for air and surfaces, and ICU-acquired staphylococcal infection. Whole-cell genomic typing (WGS) demonstrated possible transmission pathways between reservoirs. RESULTS: Frequently touched sites were more likely to be contaminated (>12 cfu/cm2; p = 0.08). Overall, 235 of 500 (47%) sites failed the surface standard (≤2.5 cfu/cm2); 20 of 40 (50%) passive air samples failed the "Index of Microbial Air" standard (2 cfu/9 cm plate/h), and 15/40 (37.5%) air samples failed the air standard (<10 cfu/m3). Settle plate data were closer to surface counts than automated air data; the surface count most likely to reflect pass/fail rates for air was 5 cfu/cm2. Surface counts/bed were associated with staphylococcal infection rates (p = 0.012). Of 34 pairs of indistinguishable S. aureus, 20 (59%) showed autogenous transmission, with another four (12%) occurring between patients. Four (12%) pairs linked patients with hand-touch sites and six (18%) linked airborne S. aureus, staff hands and hand-touch sites. CONCLUSION: Most ICU-acquired S. aureus infection is autogenous, while staff hands and air were rarely implicated in onward transmission. Settle plates could potentially be used for routine environmental screening. ICU staphylococcal infection is best served by admission screening, systematic cleaning and hand hygiene.


Assuntos
Infecção Hospitalar , Unidades de Terapia Intensiva , Infecções Estafilocócicas , Contaminação de Equipamentos , Humanos , Infecções Estafilocócicas/transmissão , Staphylococcus aureus/patogenicidade
13.
BMJ Case Rep ; 13(4)2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32317365

RESUMO

Cystic fibrosis (CF) is the most common life-limiting autosomal recessive genetic disorder among Caucasian populations. The majority of CF cases are diagnosed in childhood; however, increasing numbers of adults are being diagnosed with the condition. We present the case of a 65-year-old Irish woman presenting with a chronic cough and a history of recurrent respiratory tract infections. Staphylococcus aureus, Scedosporium apiospermum and Stenotrophomonas maltophilia were grown from bronchoalveolar lavage raising suspicion for CF. Sweat testing was negative; however, genetic testing revealed the presence of ∆F508 and R117H CF mutations, the latter mutation conferring a milder form of CF. The patient commenced treatment with the cystic fibrosis transmembrane conductance regulator (CFTR) potentiator medication ivacaftor to good effect. Novel CFTR potentiators and modulators have significant potential to benefit morbidity and mortality in this group. In this case, the microbiological results were key in pursuing genetic testing and diagnosing CF.


Assuntos
Aminofenóis/uso terapêutico , Líquido da Lavagem Broncoalveolar/microbiologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/diagnóstico , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Quinolonas/uso terapêutico , Idoso , Feminino , Testes Genéticos , Humanos , Mutação , Scedosporium/patogenicidade , Staphylococcus aureus/patogenicidade , Stenotrophomonas maltophilia/patogenicidade
14.
Emerg Infect Dis ; 26(8): 1939-1941, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32298228
15.
Medicine (Baltimore) ; 99(17): e19984, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332684

RESUMO

Susceptibility to infectious disease may be a marker of immunodeficiency caused by unrecognized cancer. To test the hypothesis, the risk of incident primary cancer was estimated among survivors of Staphylococcus aureus bacteremia (SAB) and compared to a random population cohort.Nation-wide population-based matched cohort study. Cases of SAB were identified from a national database and incident primary cancers were ascertained by record linkage. Incidence rate (IR) and ratio (IRR) with 95% confidence interval (CI) of 27 cancers was calculated by Poisson regression.During the first year of follow-up, 165 and 943 incident cases of cancer occurred in the case cohort (n = 12,918 (1.3%)) and the population cohort (n = 117,465 (0.8%)) for an IR of 3.78 (3.22-4.40) and 2.28 (2.14-2.43) per 100,000 person-years. The IRR was 1.65 (1.40-1.95). Of 27 cancers, 7 cancers occurred more frequently amongst cases than controls: cervical cancer (IRR 37.83 (4.23-338.47)), multiple myeloma (IRR 6.31 (2.58-15.44)), leukemia (IRR 4.73 (2.21-10.10)), sarcoma (IRR 4.73 (1.18-18.91)), liver cancer (IRR 3.64 (1.30-10.21)), pancreatic cancer (IRR 2.8 (1.27-6.16)), and urinary tract cancer (IRR 2.58 (1.23-5.39)). Compared to the control population, the risk of cancer was higher for those without comorbidity and with younger age. The overall risk of cancer during 2 to 5 years of follow-up was not increased (IRR 0.99 (95% CI: 0.89-1.11). However, the risk of pharyngeal cancer was increased (IRR 1.88 (1.04-3.39)) and the risk of liver cancer remained increased (IRR 3.93 (2.36-6.55)).The risk of primary incident cancer was 65% higher in the SAB cohort compared to the population cohort during the first year of follow-up and included 7 specific cancers. The risk was higher for those without comorbidity and with younger age. Screening for these specific cancers in selected populations may allow for earlier detection.


Assuntos
Bacteriemia/etiologia , Achados Incidentais , Neoplasias/diagnóstico , Staphylococcus aureus/patogenicidade , Adolescente , Adulto , Idoso , Bacteriemia/sangue , Bacteriemia/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Distribuição de Poisson , Fatores de Risco , Staphylococcus aureus/efeitos dos fármacos
16.
J Dairy Sci ; 103(5): 4732-4737, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32113752

RESUMO

Staphylococcus aureus is an important intramammary pathogen for dairy cows that also is remarkably important for public health. Multiple virulence factors can be involved simultaneously during the pathogenesis of a staphylococcal disease, including adhesion proteins, extracellular enzymes, and toxins. The main objective of this study was to assess virulence factors that are associated with cow intramammary infection (IMI) and of human health concern among Staph. aureus isolates obtained from bulk tank milk (BTM) and adherences on milking equipment surfaces. A total of 166 Staph. aureus isolates from 23 dairy farms were characterized according to their virulence profiles. For virulence factors of importance in IMI, the presence of the virulence markers thermonuclease (nuc) and coagulase (coa) and virulence genes such as fibronectin (fnbA) and intercellular adhesion (icaA, icaD) were assessed. For virulence factors of public health concern, presence of antimicrobial resistance (mecA and mecC) and enterotoxin (sea and seb) genes were analyzed. Among all Staph. aureus isolates, 5 virulence profiles were found; the profile nuc(+)coa(+)fnbA(+)icaA(+)icaD(+)mecA(-)mecC(-)sea(-)seb(-) was the most frequently observed (21 out of 23 dairy farms). No differences were found between the virulence profile frequencies of Staph. aureus from BTM and adherences on milking equipment surfaces. The virulence profiles most frequently observed included genes involved in the adherence and biofilm-forming ability of Staph. aureus, which could represent a potential advantage for the bacterium during the early stages of IMI colonization and for persistence on surfaces. Our results indicate a greater frequency of virulence factors of importance for IMI pathogenesis than virulence factors of public health concern, consistent with the dairy origin of isolates. The mecA, mecC, and seb genes were not observed among Staph. aureus isolates analyzed in this study. However, the sea gene was detected in 3 Staph. aureus isolated from BTM, thus posing a potential public health threat. Our results emphasize the importance of understanding the epidemiology and dynamics of Staph. aureus on dairy farms as a tool for the improvement of udder health and milk safety.


Assuntos
Biofilmes/crescimento & desenvolvimento , Mastite Bovina/microbiologia , Leite/microbiologia , Infecções Estafilocócicas/veterinária , Staphylococcus aureus/patogenicidade , Fatores de Virulência/genética , Animais , Bovinos , Chile , Coagulase/genética , Indústria de Laticínios/instrumentação , Enterotoxinas/genética , Fazendas , Feminino , Glândulas Mamárias Animais/microbiologia , Nuclease do Micrococo/genética , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/fisiologia , Virulência
17.
Biochim Biophys Acta Biomembr ; 1862(7): 183280, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32220553

RESUMO

Short linear antimicrobial peptides are attractive templates for developing new antibiotics. Here, it is described a study of the interaction between two short Trp-rich peptides, horine and verine-L, and model membranes. Isothermal titration calorimetry studies showed that the affinity of these peptides towards large unilamellar vesicles (LUV) having a lipid composition mimicking the lipid composition of S. aureus membranes is ca. 30-fold higher than that towards E. coli mimetics. The former interaction is driven by enthalpy and entropy, while the latter case is driven by entropy, suggesting differences in the forces that play a role in the binding to the two types of model membranes. Upon membrane binding the peptides acquired different conformations according to circular dichroism (CD) studies; however, in both cases CD studies indicated stacked W-residues. Peptide-induced membrane permeabilization, lipid flip-flop, molecular packing at the membrane-water interface, and lateral lipid segregation were observed in all cases. However, the extent of these peptide-induced changes on membrane properties was always higher in S. aureus than E. coli mimetics. Both peptides seem to act via a similar mechanism of membrane permeabilization of S. aureus membrane mimetics, while their mechanisms seem to differ in the case of E. coli. This may be the result of differences in both the peptides´ structure and the membrane lipid composition between both types of bacteria.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Bicamadas Lipídicas/química , Lipídeos de Membrana/química , Conformação Molecular , Sequência de Aminoácidos/genética , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/genética , Biomimética , Calorimetria , Dicroísmo Circular , Escherichia coli/química , Escherichia coli/patogenicidade , Humanos , Staphylococcus aureus/química , Staphylococcus aureus/patogenicidade , Termodinâmica , Triptofano/química , Triptofano/genética , Lipossomas Unilamelares/química
18.
Georgian Med News ; (298): 75-79, 2020 Jan.
Artigo em Russo | MEDLINE | ID: mdl-32141854

RESUMO

The article presents the results of a multicenter study of the etiology, antibiotic sensitivity and pharmacoepidemiology of infective endocarditis in the Russian Federation. The purpose of this study is to analyze the current practice of management of patients with infective endocarditis in conditions of low frequency of etiologically significant pathogens in the Russian Federation. The study included patients of both sexes of all age groups with definite and probable infective endocarditis. 406 cases of infectious endocarditis (240 in retrospect and 166 in the prospective part) were analyzed. Etiologically significant pathogen was isolated in 144 cases (35.5%). The structure of pathogens was dominated by gram (+) cocci (90.3%), most often - Staphylococcus aureus (46.5% of all isolated pathogens). Aminoglycosides (22.8%), parenteral cephalosporins of the III generation (22.1%) and glycopeptides (14.5%) were most frequently used in the course of starting antimicrobial therapy. When changing the mode of antimicrobial therapy, glycopeptides (18.6%), aminoglycosides (15.3%), fluoroquinolones (11.2%) and parenteral cephalosporins of generation III (9.5%) were most often prescribed.


Assuntos
Antibacterianos/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Cocos Gram-Positivos/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Cefalosporinas , Resistência a Medicamentos , Endocardite Bacteriana/epidemiologia , Endocardite Bacteriana/microbiologia , Feminino , Cocos Gram-Positivos/patogenicidade , Humanos , Masculino , Testes de Sensibilidade Microbiana , Farmacoepidemiologia , Estudos Prospectivos , Federação Russa/epidemiologia , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/patogenicidade
19.
PLoS One ; 15(3): e0230031, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32163464

RESUMO

We characterised 80 Staphylococcus aureus strains isolated from human patients with SSTIs at a rural hospital in Ethiopia. Susceptibility to antibiotic of all strains was tested. The MLST method was used to type and a phylogenetic analysis was conducted employing the sequences of 7 housekeeping genes. PCR amplification was used to investigate the presence of the following virulence genes in all strains: hla (α-haemolysin), tstH (toxic shock syndrome toxin), luk PV (Panton-Valentine leukocidin), fnbA (fibronectin binding protein A) and mecA (methicillin resistance). Most of the strains were resistant to penicillin and ampicillin, but only 3 strains were resistant to oxacillin, and 1 of them was a true MRSA. The MLST results showed a high diversity of sequence types (ST), 55% of which were new, and ST152 was the most prevalent. A phylogeny study showed that many of the new STs were phylogenetically related to other previously described STs, but bore little relationship to the only ST from Ethiopia described in the database. Virulence gene detection showed a high prevalence of strains encoding the hla, fnbA and pvl genes (98.77%, 96.3% and 72.84%, respectively), a low prevalence of the tst gene (13.58%) and a markedly low prevalence of MRSA (1.25%). S. aureus strains isolated from patients in a rural area in Ethiopia showed low levels of antibiotic resistance, except to penicillin. Moreover, this study reveals new STs in Eastern Africa that are phylogenetically related to other previously described STs, and confirm the high prevalence of the pvl gene and the low prevalence of MRSA on the continent.


Assuntos
Antibacterianos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Virulência/genética , Proteínas de Bactérias/classificação , Proteínas de Bactérias/genética , Toxinas Bacterianas/classificação , Toxinas Bacterianas/genética , Cefalosporinas/farmacologia , Farmacorresistência Bacteriana/genética , Etiópia , Exotoxinas/classificação , Exotoxinas/genética , Hospitais Rurais , Humanos , Leucocidinas/classificação , Leucocidinas/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Penicilinas/farmacologia , Filogenia , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/classificação , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/patogenicidade
20.
BMC Infect Dis ; 20(1): 225, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183752

RESUMO

BACKGROUND: Otitis media is inflammation of the middle ear, comprising a spectrum of diseases. It is the commonest episode of infection in children, which often occurs after an acute upper respiratory tract infection. Otitis media is ranked as the second most important cause of hearing loss and the fifth global burden of disease with a higher incidence in developing worlds like Sub-Saharan Africa and South Asia. Therefore, this systematic review is aimed to quantitatively estimate the current status of bacterial otitis media, bacterial etiology and their susceptibility profile in sub-Saharan Africa. METHODS: A literature search was conducted from major databases and indexing services including EMBASE (Ovid interface), PubMed/MEDLINE, Google Scholar, ScienceDirect, Cochrane Library, WHO African Index-Medicus and others. All studies (published and unpublished) addressing the prevalence of otitis media and clinical isolates conducted in sub-Saharan Africa were included. Format prepared in Microsoft Excel was used to extract the data and data was exported to Stata version 15 software for the analyses. Der-Simonian-Laird random-effects model at a 95% confidence level was used for pooled estimation of outcomes. The degree of heterogeneity was presented with I2 statistics. Publication bias was presented with funnel plots of standard error supplemented by Begg's and Egger's tests. The study protocol is registered on PROSPERO with reference number ID: CRD42018102485 and the published methodology is available from http://www.crd.york.ac.uk/CRD42018102485. RESULTS: A total of 33 studies with 6034 patients were included in this study. All studies have collected ear swab/discharge samples for bacterial isolation. The pooled isolation rate of bacterial agents from the CSOM subgroup was 98%, patients with otitis media subgroup 87% and pediatric otitis media 86%. A univariate meta-regression analysis indicated the type of otitis media was a possible source of heterogeneity (p-value = 0.001). The commonest isolates were P. aeruginosa (23-25%), S. aureus (18-27%), Proteus species (11-19%) and Klebsiella species. High level of resistance was observed against Ampicillin, Amoxicillin-clavulanate, Cotrimoxazole, Amoxicillin, and Cefuroxime. CONCLUSION: The analysis revealed that bacterial pathogens like P. aeruginosa and S. aureus are majorly responsible for otitis media in sub-Saharan Africa. The isolates have a high level of resistance to commonly used drugs for the management of otitis media.


Assuntos
Infecções Bacterianas/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Otite Média/microbiologia , África ao Sul do Saara/epidemiologia , Infecções Bacterianas/tratamento farmacológico , Criança , Humanos , Otite Média/tratamento farmacológico , Prevalência , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade
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