RESUMEN
A major problem today is bacterial resistance to antibiotics and the small number of new therapeutic agents approved in recent years. The development of new antibiotics capable of acting on new targets is urgently required. The filamenting temperature-sensitive Z (FtsZ) bacterial protein is a key biomolecule for bacterial division and survival. This makes FtsZ an attractive new pharmacological target for the development of antibacterial agents. There have been several attempts to develop ligands able to inhibit FtsZ. Despite the large number of synthesized compounds that inhibit the FtsZ protein, there are no quantitative structure-activity relationships (QSAR) that allow for the rational design and synthesis of promising new molecules. We present the first 3D-QSAR study of a large and diverse set of molecules that are able to inhibit the FtsZ bacterial protein. We summarize a set of chemical changes that can be made in the steric, electrostatic, hydrophobic and donor/acceptor hydrogen-bonding properties of the pharmacophore, to generate new bioactive molecules against FtsZ. These results provide a rational guide for the design and synthesis of promising new antibacterial agents, supported by the strong statistical parameters obtained from CoMFA (r(2)(pred) = 0.974) and CoMSIA (r(2)(pred) = 0.980) analyses.
Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/antagonistas & inhibidores , Benzamidas/farmacología , Proteínas del Citoesqueleto/antagonistas & inhibidores , Farmacorresistencia Bacteriana , Relación Estructura-Actividad Cuantitativa , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/química , Benzamidas/química , Diseño de Fármacos , Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Ligandos , Modelos Moleculares , Electricidad EstáticaRESUMEN
The presence of vancomycin-resistant enterococci (VRE) in our hospital prompted us to apply an appropriate method for assessing its rectal carriage. A screening method with bile-esculin azide agar plus different concentrations of vancomycin was used. The antimicrobial susceptibility study of enterococci isolated from clinical samples was also emphasized. The present study includes the surveillance and detection of VRE in our hospital during two years. A total of 260 samples corresponding to 138 patients were studied, 158 of them resulting positive. All EVR were Van A Enterococcus faecium, with MICs of vancomycin > or = 256 micrograms/ml. The analysis of susceptibility patterns shows variations with chloramphenicol, tetracycline and high level gentamicin concentrations. This method was easily applied because materials could be available in any clinical microbiology laboratory, and in our hands it has demonstrated to be useful for epidemiological surveillance for EVR.
Asunto(s)
Resistencia a Medicamentos , Enterococcus faecium/efectos de los fármacos , Infecciones por Bacterias Grampositivas/microbiología , Vancomicina/farmacología , Argentina/epidemiología , Cloranfenicol/farmacología , Farmacorresistencia Bacteriana Múltiple , Enterococcus faecium/aislamiento & purificación , Gentamicinas/farmacología , Infecciones por Bacterias Grampositivas/epidemiología , Hospitales de Distrito/estadística & datos numéricos , Humanos , Pruebas de Sensibilidad Microbiana , Estudios Retrospectivos , Tetraciclina/farmacologíaRESUMEN
The presence of vancomycin-resistant enterococci (VRE) in our hospital prompted us to apply an appropriate method for assessing its rectal carriage. A screening method with bile-esculin azide agar plus different concentrations of vancomycin was used. The antimicrobial susceptibility study of enterococci isolated from clinical samples was also emphasized. The present study includes the surveillance and detection of VRE in our hospital during two years. A total of 260 samples corresponding to 138 patients were studied, 158 of them resulting positive. All EVR were Van A Enterococcus faecium, with MICs of vancomycin > or = 256 micrograms/ml. The analysis of susceptibility patterns shows variations with chloramphenicol, tetracycline and high level gentamicin concentrations. This method was easily applied because materials could be available in any clinical microbiology laboratory, and in our hands it has demonstrated to be useful for epidemiological surveillance for EVR.
RESUMEN
The presence of vancomycin-resistant enterococci (VRE) in our hospital prompted us to apply an appropriate method for assessing its rectal carriage. A screening method with bile-esculin azide agar plus different concentrations of vancomycin was used. The antimicrobial susceptibility study of enterococci isolated from clinical samples was also emphasized. The present study includes the surveillance and detection of VRE in our hospital during two years. A total of 260 samples corresponding to 138 patients were studied, 158 of them resulting positive. All EVR were Van A Enterococcus faecium, with MICs of vancomycin > or = 256 micrograms/ml. The analysis of susceptibility patterns shows variations with chloramphenicol, tetracycline and high level gentamicin concentrations. This method was easily applied because materials could be available in any clinical microbiology laboratory, and in our hands it has demonstrated to be useful for epidemiological surveillance for EVR.