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1.
Microbiol Res ; 283: 127701, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38518451

RESUMEN

Klebsiella pneumoniae is a common opportunistic pathogen that presents significant challenges in the treatment of infections due to its resistance to multiple antibiotics. In recent years, K. pneumoniae has been reported for the development of heteroresistance, a phenomenon where subpopulations of the susceptible bacteria exhibit resistance. This heteroresistance has been associated with increased morbidity and mortality rates. Complicating matters further, its definition and detection pose challenges, often leading to its oversight or misdiagnosis. Various mechanisms contribute to the development of heteroresistance in K. pneumoniae, and these mechanisms differ among different antibiotics. Even for the same antibiotic, multiple mechanisms may be involved. However, our current understanding of these mechanisms remains incomplete, and further research is needed to gain a more comprehensive understanding of heteroresistance. While the clinical recommendation is to use combination antibiotic therapy to mitigate heteroresistance, this approach also comes with several drawbacks and potential adverse effects. In this review, we discuss the definition, detection methods, molecular mechanisms, and treatment of heterogenic resistance, aiming to pave the way for more effective treatment and management in the future. However, addressing the problem of heteroresistance in K. pneumoniae represents a long and complex journey that necessitates comprehensive research efforts.


Asunto(s)
Antibacterianos , Infecciones Bacterianas , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Klebsiella pneumoniae , Colistina , Farmacorresistencia Bacteriana , Pruebas de Sensibilidad Microbiana , Infecciones Bacterianas/tratamiento farmacológico
2.
Int J Hematol ; 89(4): 438-444, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19363708

RESUMEN

The aim of the study was to present the possible mechanisms of transforming growth factor beta 1(TGF-beta1) signal pathway during cell differentiation by studying the expression levels of six components of TGF-beta1 pathway (TGF-beta1, two TGF-beta1 receptors and three Smad proteins). The morphology change, the CD11 expression levels, and the mRNA and protein expression levels of TGF-beta1, TGF-beta ReceptorI (TbetaRI), TGF-beta ReceptorII (TbetaRII), Smad2, Smad4 and Smad7 were assessed by exposing NB4 cells to all-trans retinoid acid (ATRA) using Wright's stain, flow cytometry, real-time PCR assay and Western blot analysis. The mRNA and protein expression levels of all six components increased during NB4 cells differentiation induced by ATRA. They were most significantly increased after 24-72 h individually when cells were induced by ATRA (the mRNA and protein expression levels of TGF-beta1, TbetaRI, TbetaRII and Smad2 reached their peaks at 48 and 48 h individually after the treatment, Smad4 at 48 and 72 h, and Smad7 at 72 and 72 h). The change in mRNA expression levels was earlier than the change in the same gene controlling protein. These results indicate that the upregulation of TGF-beta1 pathway plays an important role in NB4 cells differentiation induced by ATRA.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo , Tretinoina/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Humanos , ARN Mensajero/genética , Receptores de Factores de Crecimiento Transformadores beta/genética , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/genética
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