Antibacterial, cyto and genotoxic activities of A22 compound ((S-3, 4 -dichlorobenzyl) isothiourea hydrochloride).

The A22 is a chemical compound that acts as a reversible inhibitor of a bacterial cell wall protein MreB leading the rods to the coccoid form. Thus, by changing the bacterial form, many properties can be affected, as the acquisition of nutrients, cell division, the clamping surfaces, motility and pathogenesis. Infections caused by strains of Pseudomonas aeruginosa have great clinical importance because these microorganisms can include more than one resistance mechanism acting together, limiting treatment options. Thus, it is important to investigate the action of A22 against P. aeruginosa, once there are urgent needs for new antimicrobial compounds for increase the arsenal therapeutic to treat diseases caused by this microrganism. Therefore, this study investigated for the first time the antimicrobial activity of A22 against seve standards strains of Gram negative microorganisms and twenty-eight clinical isolates of P. aeruginosa. This study performed an additional investigation to analyze the cyto and genotoxic potential effects from A22 on human peripheral blood mononuclear cells (PBMCs). The antibacterial activity of A22 was studied by broth microdilution method and time-kill assay. The cytotoxicity was evaluated by MTT assay at 24, 48 and 72 h of exposure to A22 and the genotoxicity was evaluated by the Comet assay. The susceptibility tests showed A22 has a relevant antibacterial activity against P. aeruginosa, including multidrug-resistant (MDR) clinical isolates. The A22 treatment not showed genotoxic effects against PBMCs in almost all concentrations tested at 24 and 48 h of exposure. Only for concentration of 32 µg/mL (highest tested) the damage index was significantly higher in all moments. The MTT assay demonstrated that A22 was able to maintain cell viability in all exposure times. In summary, the A22 demonstrated important anti-Pseudomonas activity and showed no cyto and genotoxic significant effect. These results need to be considered in future in vitro and in vivo studies in order to introduce the A22 as a possible therapeutic option.

Molecular characterization of Enterobacteriaceae resistant to carbapenem antimicrobials / Caracterização molecular de enterobactérias resistentes aos carbapenêmicos

ABSTRACT The present study aimed to genotypically and phenotypically characterize clinical isolates of carbapenem-resistant Enterobacteriaceae collected from inpatients at the University Hospital of Santa Maria, during seven months. Among the clinical isolates subjected to the modified Hodge test (MHT), 62.5% were positive, indicating possible production of carbapenemase. Polymerase chain reaction (PCR) demonstrated that blaKPC was the most frequently found gene (31%), followed by blaIMP (12.5%). Combined use of the methods is needed to identify carbapenem resistance in enterobacteria to prevent their spread and control the infections caused by these organisms.

RESUMO Objetivou-se caracterizar fenotípica e genotipicamente isolados clínicos de enterobactérias resistentes aos carbapenêmicos (CRE) provenientes do Hospital Universitário de Santa Maria (RS). Entre os isolados clínicos submetidos ao teste modificado de Hodge (MHT), 62,5% apresentaram positividade, indicando possível produção de carbapenemase. A reação em cadeia da polimerase (PCR) demonstrou que o blaKPC foi o gene mais encontrado (31%), seguido de blaIMP (12,5%). O uso conjunto de distintas metodologias faz-se necessário para identificar a resistência aos carbapenêmicos produzida pelas enterobactérias, de modo a auxiliar o controle de infecção prevenindo a disseminação desses microrganismos.