Escenario actual de la resistencia a la colistina mediada por plásmidos en América Latina / Current scenario of plasmid-mediated colistin resistance in Latin America

Colistin resistance can occur by chromosomal mutations and by acquisition of plasmid-carrying determinants, mainly mcr-1. In the recent years, we have observed the out-burst of this resistance gene in our region. Due to the risk of the rapid dissemination of mcr-1, this finding has worried and alerted different actors from the health field and has become one of the most prolific topics. Our review compiles available reports of well-documented mcr-1-positive strains of Enterobacteriaceae, obtained from different samples in Argentina and other countries of Latin America. Furthermore, it addresses the association of mcr-1 with ESBL resistance markers and outlines the platforms involved in their dissemination.

La resistencia a la colistina puede ocurrir por mutaciones cromosómicas o por la adquisición de determinantes localizados en plásmidos, el principal es mcr-1. En los últimos años hemos observado la explosiva aparición de este gen de resistencia en nuestra región. Debido al riesgo que implica la rápida diseminación de mcr-1, este hallazgo ha preocupado y alertado a los diferentes actores del área de la salud, y se ha convertido en uno de los temas de investigación más importantes. La presente revisión compila los informes de aislamientos portadores de mcr-1 debidamente documentados en Enterobacteriaceae, obtenidos de diferentes muestras en Argentina y otros países de América Latina. Además, aborda la asociación de mcr-1 con otros marcadores de resistencia, como las BLEE, y describe las plataformas involucradas en su diseminación.

Bacterial cheating drives the population dynamics of cooperative antibiotic resistance plasmids.

Inactivation of ß-lactam antibiotics by resistant bacteria is a 'cooperative' behavior that may allow sensitive bacteria to survive antibiotic treatment. However, the factors that determine the fraction of resistant cells in the bacterial population remain unclear, indicating a fundamental gap in our understanding of how antibiotic resistance evolves. Here, we experimentally track the spread of a plasmid that encodes a ß-lactamase enzyme through the bacterial population. We find that independent of the initial fraction of resistant cells, the population settles to an equilibrium fraction proportional to the antibiotic concentration divided by the cell density. A simple model explains this behavior, successfully predicting a data collapse over two orders of magnitude in antibiotic concentration. This model also successfully predicts that adding a commonly used ß-lactamase inhibitor will lead to the spread of resistance, highlighting the need to incorporate social dynamics into the study of antibiotic resistance.

Hydration of surfactant-modified and PEGylated cationic cholesterol-based liposomes and corresponding lipoplexes by monitoring a fluorescent probe and the dielectric relaxation time.

For the optimization of plasmid DNA (pDNA)-cationic lipid complexes and lipoplex delivery, proper indexes of the physicochemical properties of lipoplexes are required. In general, the characteristics of lipoplexes are defined by particle size and zeta-potential at various mixing ratios of cationic liposomes and pDNA. In this study, we characterized the hydration level of surfactant-modified and PEGylated cationic cholesterol-based (OH-Chol) liposomes and their lipoplexes by monitoring both the fluorescent probe laurdan and the dielectric relaxation time. Fluorescence measurement using laurdan detected hydration of the headgroup of lipids in surfactant-modified liposomes and PEGylated DOTAP-liposomes, but hardly any fluorescence was detected in PEGylated OH-Chol-liposomes because the PEG layers may extend and cover the fluorescent maker. On the other hand, the measurement of dielectric relaxation time of water molecules revealed total hydration, including hydration of the PEG layer and the headgroup of cationic lipids. Furthermore, we found an inverse correlation between hydration level and cellular uptake of PEGylated lipoplexes (R=0.946). This finding indicated that the dielectric relaxation time of water molecules provides an important indicator of hydration of liposome and lipoplexes along with the fluorescence intensity of laurdan.