RESUMO
The new prenylated phloroglucinol α-pyrones 1-3 and the new dibenzofuran 4, together with the known 23-methyl-6-O-demethylauricepyrone (5), achyrofuran (6), and 5,7-dihydroxy-3,8-dimethoxyflavone (gnaphaliin A), were isolated from the aerial parts of Achyrocline satureioides. Their structures were determined by 1D and 2D NMR spectroscopic studies, while the absolute configuration of the sole stereogenic center of 1 was established by vibrational circular dichroism measurements in comparison to density functional theory calculated data. The same (S) absolute configuration of the α-methylbutyryl chain attached to the phloroglucinol nucleus was assumed for compounds 2-6 based on biogenetic considerations. Derivatives 7-16 were prepared from 1 and 5, and the antimicrobial activities of the isolated metabolites and some of the semisynthetic derivatives against a selected panel of Gram-positive and Gram-negative bacteria, as well as a set of yeast molds, were determined.
Assuntos
Achyrocline/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Floroglucinol/isolamento & purificação , Floroglucinol/farmacologia , Pironas/isolamento & purificação , Pironas/farmacologia , Antibacterianos/química , Argentina , Flavonoides/química , Flavonoides/isolamento & purificação , Furanos/química , Furanos/isolamento & purificação , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Floroglucinol/química , Pironas/químicaRESUMO
OBJECTIVE: To determine the molecular epidemiology and presence of virulence genes in community-acquired (CA) and hospital-acquired (HA) methicillin-resistant Staphylococcus aureus (MRSA) isolates and their relationship to clinical outcomes. METHODS: An observational and prospective study of infections caused by MRSA was conducted between June 2006 and December 2007 across seven hospitals in three Colombian cities. MRSA isolates were analyzed for SCCmec. Also, pulsed-field gel electrophoresis and multilocus sequence typing were performed and 25 virulence genes were identified. RESULTS: Two hundred and seventy isolates were collected from 262 adult hospital patients with MRSA infections. Overall, 68% of the isolates were classified as HA-MRSA and 32% as CA-MRSA. We identified differences in the patterns of virulence genes: 85% of HA-MRSA isolates possessed the enterotoxin gene cluster (egc), whereas 92% of CA-MRSA isolates possessed the lukF-PV/lukS-PV genes. Multivariate analysis showed an increased risk of mortality for seg (p=0.001, odds ratio 4.73) and a protective effect for eta (p=0.018, odds ratio 0.33). CONCLUSIONS: Our study confirms that three clones of MRSA predominantly circulate in Colombia: a Chilean clone, a pediatric clone that causes HA-MRSA infections, and a USA300-related clone (SCCmec IVc) in CA-MRSA infections, which differ in the content of clinically important virulence genes. This study confirms that PVL is not a determinant of severity or mortality in CA-MRSA infections.
Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Infecção Hospitalar/epidemiologia , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/epidemiologia , Virulência/genética , Colômbia/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/microbiologia , Humanos , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Filogenia , Prevalência , Estudos Prospectivos , Infecções Estafilocócicas/microbiologia , Fatores de Virulência/genéticaRESUMO
Currently, there is a pressing need for novel antibacterial agents against drug-resistant bacteria, especially those which have been common in our communities and hospitals, such as methicillin-resistant Staphylococcus aureus (MRSA). The South American plant Achyrocline satureioides ("Marcela") has been widely used in traditional medicine for a number of diseases, including infections. Several crude extracts from this plant have shown good antimicrobial activities in vitro. In the search for the active principle(s) that confers these antimicrobial activities, we have processed the dichloromethane extract from the aerial parts of the plant. One of the isolated compounds showed extraordinary antibacterial activities against a set of clinically relevant Gram-positive strains that widely differ in their antibiogram profiles. This compound was identified as achyrofuran on the basis of its spectroscopic and physical data. We determined the MIC to be around 0.1 µM (0.07 µg/ml) for the reference methicillin-resistant and vancomycin-intermediate S. aureus strain NRS402. Moreover, nanomolar concentrations of achyrofuran killed 10(6) bacteria within 12 h. Based on the presence of the 2,2'-biphenol core, we further studied whether achyrofuran killed bacteria through a mechanism of action similar to that reported for the naturally occurring antibiotic MC21-A. Indeed, we found that achyrofuran was not bacteriolytic by itself although it greatly compromised membrane impermeability as determined by increased SYTOX Green uptake.
Assuntos
Achyrocline/química , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Furanos/farmacologia , Resistência a Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Resistência a Vancomicina/efeitos dos fármacos , Antibacterianos/isolamento & purificação , Argentina , Relação Dose-Resposta a Droga , Furanos/isolamento & purificação , Componentes Aéreos da Planta/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologiaRESUMO
BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus strains (CA-MRSA) have emerged as the causative agent of health care-associated infections. METHODS: An observational and prospective study was carried out in 5 hospitals in Bogotá, Colombia; severe MRSA infections were identified, and their origin led to classification as health care-associated (HA-MRSA), community-associated, or nosocomial infections. MRSA isolates were analyzed by SCCmec, pulsed-field gel electrophoresis, multilocus sequence typing, and virulence factors. RESULTS: Twenty-six (10.4%) CA-MRSA nosocomial infection-causing strains (eg, USA300) were detected in 250 MRSA infection isolates in mainly primary bacteremia and surgical site infections. The mortality related to nosocomial infection by CA-MRSA was 27%. CONCLUSION: The presence of nosocomial infection by CA-MRSA in Colombia was confirmed.