RESUMO
OBJECTIVES: The aim of the present study is to describe clinical aminoglycoside- or carbapenem-resistant Pseudomonas aeruginosa isolates collected between 2018 and 2019 in a hospital in Recife City, Northeastern Brazil. It was done based on phenotypic and molecular markers of antimicrobial resistance, as well as on the clonal diversity of the investigated isolates. METHODS: Thirty-four carbapenem- and/or aminoglycoside-resistant P. aeruginosa isolates were collected in a hospital in Recife City-PE, Brazil. Their antimicrobial susceptibility profile was identified based on the automated BD Phoenix ™ system. In addition, broth microdilution was performed to determine the MICs of tobramycin and polymyxin B. Eventually, isolates were subjected to PCR and sequencing in order to detect the carbapenemase enzyme (blaKPC, blaNDM, blaVIM, blaSPM-1, and blaIMP) and 16S rRNA methylase (armA, rmtB, rmtD, rmtF, and rmtG) genes; ERIC-PCR was conducted for clonal profile determination purposes. RESULTS: Thirty-four of the 64 isolates evaluated in the present study were selected for complementary molecular phenotypic tests, based on sample inclusion criteria. The blaKPC and blaVIM-2 genes were identified in 32.4% (11/34) and 38.2% (13/34) of tested isolates, respectively. The rmtD1 gene was detected in 32.4% (11/34) of analyzed isolates. Eight isolates carried both the blaKPC and rmtD1 genes, whereas blaVIM-2 and rmtD1 genes co-occurrence was detected in three strains; one isolate had all blaKPC, blaVIM-2, and rmtD1 genes. ERIC-PCR molecular typing has evidenced cross-transmission of three pathogenic clones among patients in the hospital. CONCLUSIONS: The present study is a pioneer in describing isolates harboring both blaVIM-2 and rmtD1 genes. Moreover, it emphasizes the need of conducting local molecular epidemiology studies at different time intervals in order to monitor measures adopted to prevent nosocomial infections in different hospital units.
Assuntos
Proteínas de Bactérias , Infecções por Pseudomonas , Pseudomonas aeruginosa , Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Brasil , Carbapenêmicos/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , RNA Ribossômico 16S/genética , beta-Lactamases/genéticaRESUMO
During evolution, parasitic microorganisms have faced the challenges of adapting to different environments to colonize a variety of hosts. Giardia lamblia, a common cause of intestinal disease, has developed fascinating strategies to adapt both outside and inside its host's intestine, such as trophozoite differentiation into cyst and the switching of its major surface antigens. How gene expression is regulated during these adaptive processes remains undefined. Giardia lacks some typical eukaryotic features, like canonical transcription factors, linker histone H1, and complex promoter regions; suggesting that post-transcriptional and translational control of gene expression is essential for parasite survival. However, epigenetic factors may also play critical roles at the transcriptional level. Here, we describe the most common post-translational histone modifications; characterize enzymes involved in these reactions, and analyze their association with the Giardia's differentiation processes. We present evidence that NAD+-dependent and NAD+-independent histone deacetylases regulate encystation; however, a unique NAD+-independent histone deacetylase modulate antigenic switching. The rates of acetylation of H4K8 and H4K16 are critical for encystation, whereas a decrease in acetylation of H4K8 and methylation of H3K9 occur preferentially during antigenic variation. These results show the complexity of the mechanisms regulating gene expression in this minimalistic protozoan parasite.
Assuntos
Variação Antigênica , Giardia lamblia/imunologia , Giardia lamblia/metabolismo , Histonas/metabolismo , Acetilação/efeitos dos fármacos , Variação Antigênica/efeitos dos fármacos , Eucromatina/metabolismo , Giardia lamblia/citologia , Giardia lamblia/genética , Heterocromatina/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Histonas/química , Lisina/metabolismo , NAD/metabolismo , Processamento de Proteína Pós-Traducional/efeitos dos fármacosAssuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Infecções por Escherichia coli/veterinária , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Genes Bacterianos , Doenças dos Cavalos/microbiologia , Animais , Brasil , DNA Bacteriano/química , DNA Bacteriano/genética , Escherichia coli/enzimologia , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Cavalos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Análise de Sequência de DNARESUMO
Relatos mundiais têm documentado a problemática da endemicidade de isolados clínicos de Pseudomonas aeruginosa multirresistente (MDR) aliada a elevados índices de morbidade/mortalidade. No Brasil, surtos de infecção ocasionados por P. aeruginosa têm sido relacionados com uma disseminação clonal da espécie. Atualmente, as opções terapêuticas para o tratamento das infecções causadas por esse microrganismo são limitadas, muitas vezes restringindo-se ao uso de carbapenêmicos (p. ex., imipenem [IPM]). Assim, a resistência ao IPM é uma questão de saúde pública, uma vez que esse antibiótico é empregado como último recurso no tratamento de infecções de origem hospitalar, causadas por bactérias Gram-negativas multirresistentes. No Brasil, os principais mecanismos relacionados com fenótipos multirresistentes de P. aeruginosa são produção de metalobetalactamase (MBL) do tipo SPM-1, presença de metilase 16S rRNA RmtD, perda de porina OprD e superexpressão de bombas de efluxo, o que pode explicar os altos índices de resistência a carbapenêmicos e aminoglicosídeos. A emergência de cepas com essas características é preocupante, tendo em vista a escassez de terapias efetivas no tratamento de infecções por esse patógeno. Finalmente, com base em relatos nacionais, publicados por diferentes grupos de pesquisa, podemos deduzir que a convergência de múltiplos mecanismos de resistência em P. aeruginosa tem sido um evento favorável para a seleção de diferentes clones endêmicos multirresistentes disseminados no Brasil.
Global reports have documented the endemicity of multidrug-resistant (MDR) Pseudomonas aeruginosa associated with high levels of morbidity/mortality. In Brazil, outbreaks of MDR P. aeruginosa have been related to clonal dissemination. Currently, therapeutic options for the treatment of these infections are restricted to carbapenemic antibiotics (i.e., imipenem [IPM]). Thus, carbapenem resistance is a public health issue, since carbapenems are considered the last resort to nosocomial infections caused by MDR Gram-negative bacteria. In Brazil, the main mechanisms associated with MDR P. aeruginosa phenotypes are metallo-betalactamase (MBL) production (SPM-1 enzyme), presence of 16S rRNA methylase RmtD, loss of OprD porin, and overexpression of efflux pumps, which may explain the high level of carbapenem and aminoglycoside resistance. Accordingly, the emergence and dissemination of MDR strains is worrisome. Finally, based on national reports published by different groups of investigators, it is deduced that the convergence of multiple mechanisms of P. aeruginosa resistance has played a major role in the selection of endemic MDR clones widespread in Brazil.