Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20.687
Filtrar
1.
Pan Afr Med J ; 39: 84, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34466186

RESUMO

The treatment of acute osteomyelitis is becoming more challenging since the emergence of community-acquired methicillin-resistant Staphylococcus aureus. We collected data on all patients with acute osteomyelitis caused by this germ over a period of 21 years (January 1995-December 2016) and we analyzed the peculiarities of this disorder. Our case series includes 15 children, with an average age of 9 years. All patients had affected lower limb. Local trauma was reported in 8 cases and skin carriage in 4 cases. Acute onset was reported in 12 cases associated with pseudo-paralysis of the affected limb. One patient had Staphylococcus aureus pulmonary infection with signs of septicopyemia. Blood culture was positive in 8 cases. In one case PCR assay for detection of Panton-Valentine leukocidin was performed with positive result. All these patients underwent surgical debridement and received secondarily adapted empirical antibiotic therapy. Outcome was good in 8 cases and poor in the other cases, with transition to a chronic state in 6 cases and one case of death. Pathological fracture was reported in 3 cases. Osteomyelitis cause by community-acquired methicillin-resistant Staphylococcus aureus is associated with a pejorative outcome. Recognizing the clinical and paraclinical signs of these infections is essential for a specific and early therapeutic management.


Assuntos
Infecções Comunitárias Adquiridas/diagnóstico , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Osteomielite/diagnóstico , Infecções Estafilocócicas/diagnóstico , Doença Aguda , Adolescente , Antibacterianos/administração & dosagem , Criança , Pré-Escolar , Terapia Combinada , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/terapia , Desbridamento/métodos , Feminino , Humanos , Masculino , Osteomielite/microbiologia , Osteomielite/terapia , Estudos Retrospectivos , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/terapia
2.
Eur J Med Res ; 26(1): 91, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380556

RESUMO

We present a case of bacterial endocarditis with both methicillin-sensitive and methicillin-resistant Staphylococcus aureus, which based on typing, originated from two distinct clones. Such a case may be misinterpreted by microbiology lab automation to be a monoclonal multi-drug resistant Staphylococcus aureus, while simple microbiology techniques will instantly reveal distinct clonality.


Assuntos
Endocardite Bacteriana/microbiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/microbiologia , Adulto , Coinfecção , Farmacorresistência Bacteriana , Endocardite Bacteriana/patologia , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Infecções Estafilocócicas/patologia
3.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360873

RESUMO

Staphylococcus aureus is a commensal bacterium that causes severe infections in soft tissue and the bloodstream. During infection, S. aureus manipulates host cell response to facilitate its own replication and dissemination. Here, we show that S. aureus significantly decreases the level of SUMOylation, an essential post-translational modification, in infected macrophages 24 h post-phagocytosis. The reduced level of SUMOylation correlates with a decrease in the SUMO-conjugating enzyme Ubc9. The over-expression of SUMO proteins in macrophages impaired bacterial intracellular proliferation and the inhibition of SUMOylation with ML-792 increased it. Together, these findings demonstrated for the first time the role of host SUMOylation response toward S. aureus infection.


Assuntos
Interações entre Hospedeiro e Microrganismos/imunologia , Macrófagos/imunologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/imunologia , Animais , Macrófagos/citologia , Camundongos , Células RAW 264.7 , Sumoilação , Enzimas de Conjugação de Ubiquitina/imunologia
4.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445550

RESUMO

Within-host adaptation is a typical feature of chronic, persistent Staphylococcus aureus infections. Research projects addressing adaptive changes due to bacterial in-host evolution increase our understanding of the pathogen's strategies to survive and persist for a long time in various hosts such as human and bovine. In this study, we investigated the adaptive processes of S. aureus during chronic, persistent bovine mastitis using a previously isolated isogenic strain pair from a dairy cow with chronic, subclinical mastitis, in which the last variant (host-adapted, Sigma factor SigB-deficient) quickly replaced the initial, dominant variant. The strain pair was cultivated under specific in vitro infection-relevant growth-limiting conditions (iron-depleted RPMI under oxygen limitation). We used a combinatory approach of surfaceomics, molecular spectroscopic fingerprinting and in vitro phenotypic assays. Cellular cytotoxicity assays using red blood cells and bovine mammary epithelial cells (MAC-T) revealed changes towards a more cytotoxic phenotype in the host-adapted isolate with an increased alpha-hemolysin (α-toxin) secretion, suggesting an improved capacity to penetrate and disseminate the udder tissue. Our results foster the hypothesis that within-host evolved SigB-deficiency favours extracellular persistence in S. aureus infections. Here, we provide new insights into one possible adaptive strategy employed by S. aureus during chronic, bovine mastitis, and we emphasise the need to analyse genotype-phenotype associations under different infection-relevant growth conditions.


Assuntos
Adaptação Fisiológica , Hemólise , Adaptação ao Hospedeiro , Glândulas Mamárias Animais/patologia , Mastite Bovina/patologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/patogenicidade , Animais , Apoptose , Bovinos , Feminino , Glândulas Mamárias Animais/microbiologia , Mastite Bovina/microbiologia , Fenótipo
5.
J Med Microbiol ; 70(8)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34338626

RESUMO

Introduction. Biofilm formation is a major virulence factor associated with Staphylococcus aureus infections. However, the influence of plasma proteins on biofilm formation of clinical isolates in vitro remains unclear.Hypotheses. We hypothesized that coating surfaces with plasma proteins might induce biofilm formation by S. aureus of different clonal lineages.Aim. To evaluate biofilm production by clinical S. aureus isolates of different clonal lineages isolated in Rio de Janeiro hospitals and investigated the presence of biofilm-associated genes.Methodology. This study assessed biofilm production of 60 S. aureus isolates in polystyrene microtitre plates with and without fibrinogen or fibronectin. The biochemical composition of the biofilm matrices was determined and the biofilm formation on fibrinogen-coated surfaces was also evaluated by confocal laser scanning microscopy. The presence of biofilm-related genes was detected by PCR, and the typing and functionality of agr operon was also evaluated.Results. Most of the isolates (45 %) were weak biofilm producers or non-producers. However, most of them presented a significant increase in biofilm production on plates covered with plasma proteins. There was no significant difference in biofilm formation between methicillin-resistant and -susceptible S. aureus isolates, or between different clonal lineages, except for ST30-IV (weak producers) and ST239-III (strong producers). The fnbB gene was associated with higher biofilm production.Conclusion. An increase in biofilm production in the presence of plasma proteins highlights the importance of investigating biofilm formation by S. aureus clinical isolates under different conditions since this virulence factor contributes to persistent infections and increased resistance to antimicrobials.


Assuntos
Biofilmes/crescimento & desenvolvimento , Fibrinogênio , Fibronectinas , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Staphylococcus aureus/patogenicidade , Adesinas Bacterianas/genética , Aderência Bacteriana/genética , Proteínas de Bactérias/genética , Genes Bacterianos , Genótipo , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/fisiologia , Óperon , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/fisiologia , Transativadores/genética
6.
J Med Microbiol ; 70(7)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34269673

RESUMO

Introduction. Staphylococcus aureus is a major cause of hospital infections worldwide. Awareness towards methicillin-resistant S. aureus (MRSA) infections is high but attention towards borderline oxacillin-resistant S. aureus (BORSA) is limited, possibly due to an underestimated clinical relevance, presumption of low incidence and diagnostic limitations.Gap statement. BORSA surveillance has not been routinely implemented, and thus consensus with regard to a definition and infection control measures is lacking.Aim. Our goals were to investigate the occurrence, molecular characteristics and clinical manifestations of BORSA infections in the hospital setting.Methodology. Following an increased incidence in 2016, BORSA cases in 2014/2016 (in our institution) were more specifically evaluated. Medical records were reviewed to investigate epidemiological links, clinical characteristics and outcomes. Resistance and virulence markers were assessed by whole genome sequencing (WGS). Conventional methods: amplified fragment length polymorphism (AFLP) ; multilocus sequence typing (MLST) and multiple locus variable-number tandem repeat analysis (MLVA) were compared with core genome MLST (cgMLST) and whole-genome single nucleotide polymorphism (wgSNP) analysis to confirm genetic clusters.Results. From 2009 to 2013, BORSA comprised 0.1 % of all clinical S. aureus strains. In 2016, the incidence was six-fold higher in comparison to the baseline. Whole-genome SNP and cgMLST confirmed two BORSA clusters among patients with dermatological conditions. Patients with BORSA presented with skin infections, and one case developed a severe invasive infection with a fatal outcome. Infection control measures successfully prevented further transmission in both clusters. WGS findings showed that BORSA strains carried multiple resistance and virulence genes with increased pathogenic potential.Conclusion. WGS and cgMLST effectively characterized and confirmed BORSA clusters among at-risk patients with clinical manifestations ranging from mild skin infections to life-threatening bacteraemia. Clinical awareness and active monitoring are therefore warranted for the timely implementation of infection control measures to prevent BORSA transmission in high-risk patients.


Assuntos
Antibacterianos/farmacologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana , Oxacilina/farmacologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Infecção Hospitalar/transmissão , Genoma Bacteriano , Hospitais/estatística & dados numéricos , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Polimorfismo de Nucleotídeo Único , Infecções Estafilocócicas/transmissão , Staphylococcus aureus/classificação , Staphylococcus aureus/efeitos dos fármacos , Sequenciamento Completo do Genoma
7.
Bone Joint J ; 103-B(7 Supple B): 9-16, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34192921

RESUMO

AIMS: The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time. METHODS: Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces. RESULTS: All animals tolerated surgery well, with preservation of gait mechanics and weightbearing in control individuals. Postoperative in vivo imaging demonstrated predictable evolution of infection with logarithmic signal decay coinciding with abscess formation. Postmortem mCT qualitative volumetric analysis showed high contact area and both cement-bone and cement-implant interdigitation. FE-SEM revealed biofilm formation on the prosthetic head. CONCLUSION: This study demonstrates the utility of a new, high-fidelity model of in vivo PJI using cemented hip hemiarthroplasty in rats. Inoculation with bioluminescent bacteria allows for non-invasive, real-time monitoring of infection. Cite this article: Bone Joint J 2021;103-B(7 Supple B):9-16.


Assuntos
Hemiartroplastia , Prótese de Quadril , Infecções Relacionadas à Prótese/diagnóstico por imagem , Infecções Relacionadas à Prótese/microbiologia , Infecções Estafilocócicas/diagnóstico por imagem , Infecções Estafilocócicas/microbiologia , Animais , Distinções e Prêmios , Biofilmes , Cimentos Ósseos , Modelos Animais de Doenças , Marcha , Masculino , Microscopia Eletrônica de Varredura , Impressão Tridimensional , Ratos , Ratos Sprague-Dawley , Microtomografia por Raio-X
8.
Expert Opin Drug Metab Toxicol ; 17(9): 1039-1048, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34225556

RESUMO

Introduction: Usage of ceftriaxone-based therapy to treat Methicillin-Susceptible Staphylococcus aureus (MSSA) infections is a controversial issue, from in vitro to clinical studies.Area covered: We conducted a literature review using PubMed of articles with ceftriaxone pharmacokinetics parameters and built a probability of target attainment (PTA) based on PK values from stable conditions (non-critically-ill patients) with goals of fT>55%, fT>75%, and fT>100%. Ceftriaxone's minimal inhibitory concentration from 31 MSSA strains (0.25-64 mg/L) was used to build the cumulative fraction response (CFR). The isolates were clinically relevant from blood, bronchoalveolar lavage, and soft tissue biopsy.Expert opinion: The results from controversies about using ceftriaxone for MSSA infections have been commonly addressed in the literature. However, variables such as (i) pharmacokinetic profile, (ii) pharmacodynamic target, (iii) site of infection, and (iv) MIC distributions may influence divergences. From this pharmacokinetics-pharmacodynamics perspective, ceftriaxone may be a reasonable option for MSSA infections when the MIC50 and MIC90 were 4 mg/L and 8 mg/L. CFR analysis demonstrated that ceftriaxone 1 g q24 h could be used if bacteriostasis is the aim (fT>55%), while 1 g q12h should be used for bactericidal effects (fT>75% or fT>100%). These dosing regimens should be considered in other clinical trials.


Assuntos
Antibacterianos/administração & dosagem , Ceftriaxona/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Ceftriaxona/farmacocinética , Ceftriaxona/farmacologia , Esquema de Medicação , Farmacorresistência Bacteriana , Humanos , Meticilina/farmacologia , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação
9.
Methods Mol Biol ; 2341: 127-131, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34264468

RESUMO

Staphylococcus aureus is an important human pathogen that causes a plethora of diverse infections within the human host that range in severity from the relatively minor to the severe. Of note, bloodstream infections caused by this organism result in high mortality rates, often following failed rounds of surgical and antibiotic intervention. The capacity for S. aureus to exist in blood is driven by myriad virulence factors that engage in a manipulation of various host responses to evade destruction and ensure survival. These include both secreted elements, such as coagulase and von Willebrand factor protein, as well as surface displayed factors, including clumping factor A and fibronectin binding protein A. In addition to this, there are a number of other loci within the S. aureus genome whose products have been shown to contribute to blood survival by more indirect means. Accordingly, ex vivo whole human blood survival assays are often used as a preliminary study to investigate host-bacterial interactions in an effort to delineate the pathogenicity of S. aureus strains. Herein we provide a detailed assessment of the protocol required to perform such studies.


Assuntos
Sangue/microbiologia , Staphylococcus aureus/crescimento & desenvolvimento , Fatores de Virulência/metabolismo , Proteínas de Bactérias/metabolismo , Sangue/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Viabilidade Microbiana , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/metabolismo , Staphylococcus aureus/patogenicidade
10.
Commun Biol ; 4(1): 836, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226658

RESUMO

Transporters play vital roles in acquiring antimicrobial resistance among pathogenic bacteria. In this study, we report the X-ray structure of NorC, a 14-transmembrane major facilitator superfamily member that is implicated in fluoroquinolone resistance in drug-resistant Staphylococcus aureus strains, at a resolution of 3.6 Å. The NorC structure was determined in complex with a single-domain camelid antibody that interacts at the extracellular face of the transporter and stabilizes it in an outward-open conformation. The complementarity determining regions of the antibody enter and block solvent access to the interior of the vestibule, thereby inhibiting alternating-access. NorC specifically interacts with an organic cation, tetraphenylphosphonium, although it does not demonstrate an ability to transport it. The interaction is compromised in the presence of NorC-antibody complex, consequently establishing a strategy to detect and block NorC and related transporters through the use of single-domain camelid antibodies.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Anticorpos de Domínio Único/metabolismo , Staphylococcus aureus/metabolismo , Animais , Antibacterianos/química , Antibacterianos/metabolismo , Proteínas de Bactérias/química , Sítios de Ligação , Cristalografia por Raios X , Humanos , Proteínas de Membrana Transportadoras/classificação , Proteínas de Membrana Transportadoras/genética , Modelos Moleculares , Filogenia , Ligação Proteica , Conformação Proteica , Anticorpos de Domínio Único/química , Infecções Estafilocócicas/microbiologia
11.
Molecules ; 26(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201372

RESUMO

A novel pleuromutilin derivative, 22-(4-(2-(4-nitrophenyl-piperazin-1-yl)-acetyl)-piperazin-1-yl)-22-deoxypleuromutilin (NPDM), was synthesized in our laboratory and proved excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). In this study, more methods were used to further study its preliminary pharmacological effect. The antibacterial efficacy and toxicity of NPDM were evaluated using tiamulin as the reference drug. The in vitro antibacterial activity study showed that NPDM is a potent bactericidal agent against MRSA that induced time-dependent growth inhibition and a concentration-dependent post-antibiotic effect (PAE). Toxicity determination showed that the cytotoxicity of NPDM was slightly higher than that of tiamulin, but the acute oral toxicity study proved that NPDM was a low-toxic compound. In an in vivo antibacterial effect study, NPDM exhibited a better therapeutic effect than tiamulin against MRSA in a mouse thigh infection model as well as a mouse systemic infection model with neutropenia. The 50% effective dose (ED50) of NPDM in a Galleria mellonella infection model was 50.53 mg/kg. The pharmacokinetic properties of NPDM were also measured, which showed that NPDM was a rapid elimination drug in mice.


Assuntos
Antibacterianos/farmacologia , Diterpenos/farmacologia , Nitrofenóis/farmacologia , Piperazina/farmacologia , Compostos Policíclicos/farmacologia , Animais , Linhagem Celular , Insetos/microbiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana/métodos , Ratos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia
12.
Infect Immun ; 89(9): e0015321, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34125598

RESUMO

Staphylococcus aureus is associated with the development of persistent and severe inflammatory diseases of the upper airways. Yet, S. aureus is also carried asymptomatically in the sinonasal cavity of ∼50% of healthy adults. The causes of this duality and host and microbial factors that tip the balance between S. aureus pathogenesis and commensalism are poorly understood. We have shown that by degrading mucins, anaerobic microbiota support the growth of airway pathogens by liberating metabolites that are otherwise unavailable. Given the widely reported culture-based detection of anaerobes from individuals with chronic rhinosinusitis (CRS), here we tested our hypothesis that CRS microbiota is characterized by a mucin-degrading phenotype that alters S. aureus physiology. Using 16S rRNA gene sequencing, we indeed observed an increased prevalence and abundance of anaerobes in CRS relative to non-CRS controls. PICRUSt2-based functional predictions suggested increased mucin degradation potential among CRS microbiota that was confirmed by direct enrichment culture. Prevotella, Fusobacterium, and Streptococcus comprised a core mucin-degrading community across CRS subjects that generated a nutrient pool that augmented S. aureus growth on mucin as a carbon source. Finally, using transcriptome sequencing (RNA-seq), we observed that S. aureus transcription is profoundly altered in the presence of mucin-derived metabolites, though expression of several key metabolism- and virulence-associated pathways varied between CRS-derived bacterial communities. Together, these data support a model in which S. aureus metabolism and virulence in the upper airways are dependent upon the composition of cocolonizing microbiota and the metabolites they exchange.


Assuntos
Interações Hospedeiro-Patógeno , Interações Microbianas , Microbiota , Infecções Respiratórias/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/fisiologia , Anaerobiose , Doença Crônica , Suscetibilidade a Doenças , Humanos
13.
J Mater Chem B ; 9(23): 4735-4745, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34095948

RESUMO

Large bone defects face a high risk of infection, which can also lead to bone homeostasis disorders. This seriously hinders the bone healing process; therefore, the help of a dual-functional scaffold that has both anti-infection and bone-homeostasis-regulating capacities is needed in the treatment of infected bone defects. In this study, a 3D printed dual-functional scaffold composed of poly-ε-caprolactone (PCL), mesoporous bioactive glasses (MBG), and gallium (Ga) was produced. In vitro experiments demonstrated the excellent antibacterial ability of the PCL/MBG/Ga scaffold against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). The scaffold also significantly inhibited osteoclastic activity and promoted osteogenic differentiation. Furthermore, a rabbit model with an infected bone defect in the radius was used to evaluate the in vivo bone healing capability of PCL/MBG/Ga. The results demonstrate that the PCL/MBG/Ga scaffold can significantly accelerate bone healing and prevent bone resorption, suggesting its potential for application in repairing infected bone defects.


Assuntos
Anti-Infecciosos/uso terapêutico , Osso e Ossos/patologia , Infecções por Escherichia coli/tratamento farmacológico , Gálio/química , Homeostase , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Impressão Tridimensional , Infecções Estafilocócicas/tratamento farmacológico , Animais , Regeneração Óssea , Osso e Ossos/microbiologia , Coelhos , Infecções Estafilocócicas/microbiologia , Tecidos Suporte , Cicatrização
14.
FASEB J ; 35(7): e21695, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34160101

RESUMO

Chronic wounds are a major disease burden worldwide. The breach of the epithelial barrier facilitates transition of skin commensals to invasive facultative pathogens. Therefore, we investigated the potential effects of Staphylococcus aureus (SA) on dermal fibroblasts as key cells for tissue repair. In co-culture systems combining live or heat-killed SA with dermal fibroblasts derived from the BJ-5ta cell line, healthy individuals, and patients with systemic sclerosis, we assessed tissue repair including pro-inflammatory cytokines, matrix metalloproteases (MMPs), myofibroblast functions, and host defense responses. Only live SA induced the upregulation of IL-1ß/-6/-8 and MMP1/3 as co-factors of tissue degradation. Additionally, the increased cell death reduced collagen production, proliferation, migration, and contractility, prerequisite mechanisms for wound closure. Intracellular SA triggered inflammatory and type I IFN responses via intracellular dsDNA sensor molecules and MyD88 and STING signaling pathways. In conclusion, live SA affected various key tissue repair functions of dermal fibroblasts from different sources to a similar extent. Thus, SA infection of dermal fibroblasts should be taken into account for future wound management strategies.


Assuntos
Fibroblastos/patologia , Dermatopatias Infecciosas/patologia , Pele/patologia , Infecções Estafilocócicas/complicações , Staphylococcus aureus/patogenicidade , Cicatrização , Adulto , Idoso , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Células Cultivadas , Feminino , Fibroblastos/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pele/microbiologia , Dermatopatias Infecciosas/microbiologia , Infecções Estafilocócicas/microbiologia , Adulto Jovem
15.
Artigo em Inglês | MEDLINE | ID: mdl-34094618

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the leading causes of both nosocomial and community infections worldwide. In the Philippines, MRSA rates have remained above 50% since 2010, but resistance to other antibiotics, including vancomycin, is low. The MRSA burden can be partially attributed to pathogen-specific characteristics of the circulating clones, but little was known about the S. aureus clones circulating in the Philippines. We sequenced the whole genomes of 116 S. aureus isolates collected in 2013-2014 within the Antimicrobial Resistance Surveillance Program. The multilocus sequence type, spa type, SCCmec type, presence of antimicrobial resistance (AMR) determinants and virulence genes and relatedness between the isolates were all derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined. The MRSA population in the Philippines comprised a limited number of genetic clones, including several international epidemic clones, such as CC30-spa-t019-SCCmec-IV-PVL+, CC5-SCCmec-typeIV and ST239-spa-t030-SCCmec-typeIII. The CC30 genomes were related to the South-West Pacific clone but formed a distinct, diverse lineage, with evidence of global dissemination. We showed independent acquisition of resistance to sulfamethoxazole/trimethoprim in various locations and genetic clones but mostly in paediatric patients with invasive infections. The concordance between phenotypic and genotypic resistance was 99.68% overall for eight antibiotics in seven classes. We have made the first comprehensive genomic survey of S. aureus in the Philippines, which bridges the gap in genomic data from the Western Pacific Region and will constitute the genetic background for contextualizing prospective surveillance.


Assuntos
Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/microbiologia , Genômica , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Filipinas/epidemiologia , Infecções Estafilocócicas/epidemiologia
17.
Science ; 372(6547): 1169-1175, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34112687

RESUMO

Emergent resistance to all clinical antibiotics calls for the next generation of therapeutics. Here we report an effective antimicrobial strategy targeting the bacterial hydrogen sulfide (H2S)-mediated defense system. We identified cystathionine γ-lyase (CSE) as the primary generator of H2S in two major human pathogens, Staphylococcus aureus and Pseudomonas aeruginosa, and discovered small molecules that inhibit bacterial CSE. These inhibitors potentiate bactericidal antibiotics against both pathogens in vitro and in mouse models of infection. CSE inhibitors also suppress bacterial tolerance, disrupting biofilm formation and substantially reducing the number of persister bacteria that survive antibiotic treatment. Our results establish bacterial H2S as a multifunctional defense factor and CSE as a drug target for versatile antibiotic enhancers.


Assuntos
Antibacterianos/farmacologia , Cistationina gama-Liase/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Sulfeto de Hidrogênio/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/metabolismo , Biofilmes , Cristalografia por Raios X , Cistationina gama-Liase/química , Cistationina gama-Liase/genética , Cistationina gama-Liase/metabolismo , Descoberta de Drogas , Farmacorresistência Bacteriana , Sinergismo Farmacológico , Tolerância a Medicamentos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/crescimento & desenvolvimento , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/enzimologia , Staphylococcus aureus/genética , Staphylococcus aureus/crescimento & desenvolvimento
18.
Int J Mol Sci ; 22(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068733

RESUMO

Wound infections are considered a major cause for wound-associated morbidity. There is a high demand for alternative, robust, and affordable methods that can provide relatable and reproducible results when testing topical treatments, both in research and in the pharmaceutical industry. Here we present an ex vivo wound infection model using porcine skin and a burn wounding method, allowing for the efficacy evaluation of topical antimicrobial formulations. Utilizing this model, we demonstrate the potential of topical treatments after infecting the wounds with clinically significant bacteria, P. aeruginosa and S. aureus. We show that the method is compatible with several analytical tools used to analyze infection and antimicrobial effects. Both bacterial strains successfully infected the wound surface, as well as deeper regions of the tissue. Quantification of viable bacteria on the wound surface and in the tissue, longitudinal measurements of bioluminescence, fluorescence microscopy, and scanning electron microscopy were used to confirm the effects of antibacterial treatments. Furthermore, we show that biofilms are formed on the wound surface, indicating that the demonstrated method mirrors typical in vivo infections.


Assuntos
Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Queimaduras/tratamento farmacológico , Infecção dos Ferimentos/tratamento farmacológico , Administração Tópica , Animais , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Queimaduras/patologia , Modelos Animais de Doenças , Composição de Medicamentos/métodos , Humanos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Suínos , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia
19.
BMC Infect Dis ; 21(1): 578, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34130629

RESUMO

BACKGROUND: Antibiotic Resistance is an imminent global public health threat. Antibiotic resistance emerged in healthcare settings and has now moved on to the community settings. This study was conducted to identify the rates of asymptomatic colonization with selected antibiotic resistant organisms, (Methicillin Resistant Staphylococcus aureus (MRSA), Extended Spectrum Beta Lactamase (ESBL) producing Escherichia coli and Klebsiella spp and carbapenem resistant E.coli and Klebsiella spp) - among a group of university students in Sri Lanka. Identification of genetic determinants of MRSA and ESBL was an additional objective of the study. METHODS: A self - collected nasal swab and a peri-rectal swab collected after passing stools were obtained. Routine microbiological methods were used for the isolation S.aureus from the nasal swab and E.coli and Klebsiella species from the peri-rectal swab. Antibiotic sensitivity testing was performed as recommended by clinical and laboratory standard institute (CLSI). Three (3) genes that are responsible for ESBL production; blaCTX-M, blaSHV, and blaTEM were tested using previously described primers and PCR procedures. Identification of MecA and PVL genes attributed to MRSA was also done with PCR. RESULTS: A total of 322 participants between 21 and 28 years were recruited representing 5 different faculties of study. Seventy one (22.0%) were colonized with S.aureus and 14 among them with MRSA, making the MRSA colonization rate of 4.3%. Forty five (15%) of the participants were colonized with an ESBL producing E.coli or Klebsiella spp. No one was colonized with carbapenem resistant E.coli or Klebsiella species. Of the 45 ESBL producers the commonest genetic determinant identified was blaCTX-M (n = 36), while 16 isolates had blaTEM and 7 had blaSHV. Similarly, of the 14 isolates identified as MRSA, 3 (21.4%) were found to be PVL positive while 11 (78.6%) were MecA positive. CONCLUSIONS: A high rate of colonization with ESBL producing E.coli and Klebsiella species was noted in our study group.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Farmacorresistência Bacteriana , Universidades , Adulto , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Carbapenêmicos/uso terapêutico , Estudos de Coortes , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Klebsiella/isolamento & purificação , Infecções por Klebsiella/microbiologia , Masculino , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Sri Lanka , Infecções Estafilocócicas/microbiologia , Estudantes , Adulto Jovem , beta-Lactamases/genética
20.
J Vet Diagn Invest ; 33(4): 655-663, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34075814

RESUMO

The use of oral fluid (OF) to detect zoonotic pathogens in pigs has been only scarcely assessed. We evaluated OF as a potential specimen for detection by culture of methicillin-resistant Staphylococcus aureus (MRSA) and Yersinia enterocolitica, and the detection of antibodies against Salmonella spp. and hepatitis E virus (HEV) using commercial ELISAs. Samples from 33 pig farms were collected at the beginning and end of the fattening period. Results of the OF samples were compared with the results of serum samples and nasal swabs from individual pigs and pen floor fecal samples, using the Cohen kappa (κ) and the McNemar test. For Salmonella spp. antibodies, OF samples were negative, although the corresponding serum samples were positive. The detection of HEV antibodies in sera and OF had agreement at the first sampling, and poor and significant agreement at the second sampling (κ = 0.185, McNemar p = 0.238; κ = 0.088, McNemar p < 0.001). At both sampling times, the detection of MRSA in nasal swabs and OF showed agreement (κ = 0.466, McNemar p = 0.077; κ = 0.603, McNemar p = 1); agreement was seen for the detection of Y. enterocolitica in fecal and OF samples (κ = 0.012, McNemar p = 0.868; κ = 0.082, McNemar p = 0.061, respectively). According to the McNemar test, the use of pen-based OFs is more feasible for the detection of MRSA and Y. enterocolitica by culture than is detection of antibodies by commercial ELISA.


Assuntos
Hepatite E/veterinária , Saliva/microbiologia , Salmonelose Animal/epidemiologia , Infecções Estafilocócicas/veterinária , Doenças dos Suínos/epidemiologia , Yersiniose/veterinária , Animais , Hepatite E/diagnóstico , Hepatite E/epidemiologia , Hepatite E/microbiologia , Vírus da Hepatite E/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Prevalência , Salmonella/isolamento & purificação , Salmonelose Animal/diagnóstico , Salmonelose Animal/microbiologia , Estudos Soroepidemiológicos , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Sus scrofa , Suínos , Doenças dos Suínos/diagnóstico , Doenças dos Suínos/microbiologia , Suíça/epidemiologia , Yersiniose/diagnóstico , Yersiniose/epidemiologia , Yersiniose/microbiologia , Yersinia enterocolitica/isolamento & purificação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...