Between adaptation and virulence:A proteomics view on Staphylococcus aureus infections

Staphylococcus aureus is one of the commonly encountered bacteria of the human microbiome. Although mostly a seemingly harmless commensal microbe, S. aureus can act as an invasive pathogen with seriously devastating effects on its host’s health and wellbeing. A wide range of infections caused by this bacterium has been reported to affect diverse parts of the human body, including the skin, soft tissues and bones, as well as important organs like the heart, kidneys and lungs. Particularly, S. aureus is infamous for being a major causative agent of respiratory tract infections that may escalate up to necrotizing pneumonia. Due to its clinical relevance, this pathogen has been intensively studied for many years. Nonetheless, further research in this field is still needed, because of the high capacity of S. aureus to evolve drug resistance, its high genomic plasticity and adaptability and, not in the last place, the plethora of niches within the human body where it can thrive and survive. In this regard, there are still many uncertainties concerning the specific adaptations carried out by S. aureus during colonization and infection of the human body, the transition between both stages, and upon the invasion of different types of host cells. To shed more light on some of these adaptations, the research described in this thesis has employed in vitro models of infection that mimic particular conditions during the infectious process with special focus on the lung epithelium. The adaptations displayed by S. aureus were monitored using advanced proteomics. Furthermore, the analyses documented in this thesis included S. aureus strains with diverse backgrounds and epidemiology to take into account the genetic diversity encountered in this species.Staphylococcus aureus ist eines der am häufigsten vorkommenden Bakterien im menschlichen Mikrobiom. Auch wenn sich S.aureus meist eher harmlos verhält, kann diese Mikrobe als invasiver Krankheitserreger bedrohliche Auswirkungen auf die Gesundheit und das Wohlbefinden von Patienten haben. Ein breites Spektrum an Infektionen, die durch dieses Bakterium ausgelöst werden, kann verschiedenste Körperteile des Menschens wie Haut, Weichteile und Knochen, sowie Lebenswichtige Organe wie das Herz, die Nieren und die Lunge betreffen. S. aureus ist insbesondere als ein Haupterreger von Atemwegsinfekten bekannt, welche sich bis zu einer nekrotisierenden Lungenentzündung entwickeln können. Aufgrund seiner klinischen Bedeutung wird dieser Kranksheitserrger bereits seit Jahren intensiv untersucht. Dennoch ist eine Erforschung von S. aureus wegen dessen Fähigkeiten Antibiotikaresistenzen zu entwickeln, der hohen genomischen Plastizität und Anpassungsfähigkeit und nicht zuletzt, der Vielzahl an Nischen im menschlichen Körper, wo es gedeihen und überleben kann, weiter notwendig. Die spezifischen Anpassungen von S. aureus während der Besiedlung und Kolonisierung des menschlichen Körpers, während des Übergangs zwischen diesen beiden Phasen sowie nach Eindringen in verschiedene Wirtszelltypen sind bisher nur unvollständig aufgeklärt. Um im Rahmen dieser Doktorabeit einige Einblicke in diese Anpassungen zu erhalten, wurden in vitro Infektionsmodelle eingesetzt, die bestimmte Bedingungen des Infektionsprozesses speziell im Lungenepithel widerspiegeln. Diese Anpassungen von S. aureus wurden mittels moderner Proteomanalysen untersucht. Weiterhin wurden im Rahmen dieser Arbeit S. aureus Stämme verschiedenen Ursprungs in die Analysen einbezogen, um auch die genetische Vielfalt dieser Spezies zu berücksichtigen

Between adaptation and virulence:A proteomics view on Staphylococcus aureus infections

Staphylococcus aureus is een reguliere bewoner van het menselijke lichaam. Ongeveer 30% van de gezonde volwassenen is drager van deze bacterie, meestal in de neus. Hoewel S. aureus dragerschap meestal symptoomloos is kan deze bacterie ziektes verwekken die in ernst variëren van een milde huidinfectie tot een levensbedreigende longontsteking. Dergelijke infecties kunnen moeilijk behandelbaar zijn, niet alleen omdat de bacterie gemakkelijk resistent wordt tegen antibiotica, maar ook omdat hij zich erg goed kan aanpassen aan de verschillende omstandigheden in en op ons lichaam. De aanpassingsmechanismen die S. aureus benut worden sinds vele jaren bestudeerd onder goed controleerbare laboratoriumcondities. Op grond hiervan kennen we veel van de basisprincipes die ten grondslag liggen aan het aanpassingsvermogen van S. aureus. Desondanks weten we nog steeds te weinig van de uitdagingen die de bacterie ondervindt, wanneer hij onze cellen en weefsels infecteert. Dit komt, doordat die condities erg complex en veranderlijk zijn en de bacterie dientengevolge vele functies tegelijk moet aanpassen. In het onderhavige promotie-onderzoek werden nieuwe technologieën ingezet om de eiwitsamenstelling van de bacterie precies te quantificeren, allereerst gedurende een infectie van humaan longepitheel en vervolgens in bacterie-isolaten die zich hebben aangepast aan infectiecondities in een ziekenhuisomgeving of onder de gezonde bevolking. De waargenomen veranderingen in eiwitsamenstelling zijn representatief voor de beslissingen die de bacterie neemt onder verschillende omstandigheden. De resultaten van dit promotie-onderzoek laten zien, dat met name aanpassingen in de bacteriële stofwisseling van eminent belang zijn tijdens een infectie en dat deze aanpassingen bepalend zijn voor de uitkomst van S. aureus infecties.Staphylococcus aureus is a regular resident of the human body. This bacterium is carried by around 30% of the healthy population, most frequently in the nasal cavity. Although carriage of S. aureus is generally asymptomatic, it is a renowned pathogen capable of causing diseases that range from mild skin infections to necrotizing pneumonia. Such infections may be difficult to treat, not only because this bacterium rapidly develops resistance to antibiotics, but also because it can effectively adapt to different environments within and around the human body. The adaptive mechanisms of S. aureus have been studied for many years in well-controlled laboratory settings. This has deepened our understanding of bacterial adaptations. Yet, the challenges imposed on the bacterium during infection of human cells and tissues are more complex, and the respective bacterial responses are still poorly understood especially since the bacterium needs to activate and modulate several adaptive pathways simultaneously. In the present PhD research, new technologies allowing precise quantification of proteins have been employed to assess the adaptive behavior of S. aureus, firstly upon invasion of lung epithelial cells, but also in response to different epidemiological conditions in the hospital and the general population. Importantly, the changes in protein abundance reflect the “decisions” taken by the pathogen in these widely differing conditions. The results presented in this thesis highlight the importance of adaptations in bacterial metabolism during infection, and they show that metabolic adaptations play critical roles in the outcome of infections caused by S. aureus

Circadian rhythms of proliferation events in two mouse carcinomas

We studied the index of DNA synthesis (DNAs) of two cellular carcinomas: the hepatocellular ES12a and the mammary TN60 of mice, throughout one circadian cycle. In the results, we observed that both tumors have circadian rhythms (CRs), but the peaks of DNAs vary. Besides, the mean of DNAs along 24 h shows significative differences, the TN60 has higher values than the ES12a. These observed CR in the DNAs index in both carcinomas mean that, at least in partly, the proliferation of cancer cells can be regulated by endocrine factor as it normally occurs in ordinary cells. The big problem we can find for the chronopharmacology is that it is impossible to know in advance the rate of proliferation of each tumor.Fil: Garcia, Marcela. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Andrini, Laura Beatríz. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Martinez, Marina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Inda, Ana. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Palma, Maria Belen. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miriuka, Santiago Gabriel. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Errecalde, Ana Lia. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentin

Análisis de la cadena de suministro de una empresa abastecedora de alimentos desde Guayaquil hacia la región insular

Siguiendo la línea de desarrollo comercial que la Región Insular ha experimentado en los últimos años, se presenta este estudio como un aporte valioso a la sociedad ecuatoriana, pues se aplican los conocimientos referentes a procesos logísticos adquiridos en la maestría: elaboración y selección de modelos de pronósticos adecuados de ventas, determinación, mejoramiento y monitoreo del nivel de servicio, y planificación financiera, que involucran el diagnóstico de la cadena de suministros de una empresa que tiene su sede en la ciudad de Guayaquil y proporciona el abastecimiento, básicamente, de productos alimenticios a las Islas Galápagos

Investigating Sentinel 2 Multispectral Imagery Efficiency in Describing Spectral Response of Vineyards Covered with Plastic Sheets

The protection of vineyards with overhead plastic covers is a technique largely applied in table grape growing. As with other crops, remote sensing of vegetation spectral reflectance is a useful tool for improving management even for table grape viticulture. The remote sensing of the spectral signals emitted by vegetation of covered vineyards is currently an open field of investigation, given the intrinsic nature of plastic sheets that can have a strong impact on the reflection from the underlying vegetation. Baring these premises in mind, the aim of the present work was to run preliminary tests on table grape vineyards covered with polyethylene sheets, using Copernicus Sentinel 2 (Level 2A product) free optical data, and compare their spectral response with that of similar uncovered vineyards to assess if a reliable spectral signal is detectable through the plastic cover. Vine phenology, air temperature and shoot growth, were monitored during the 2016 growing cycle. Twenty-four Copernicus Sentinel 2 (S2, Level 2A product) images were used to investigate if, in spite of plastic sheets, vine phenology can be similarly described with and without plastic covers. For this purpose, time series of S2 at-the-ground reflectance calibrated bands and correspondent normalized difference vegetation index (NDVI), modified soil-adjusted vegetation index, version two (MSAVI2) and normalized difference water index (NDWI) spectral indices were obtained and analyzed, comparing the responses of two covered vineyards with different plastic sheets in respect of two uncovered ones. Results demonstrated that no significant limitation (for both bands and spectral indices) was introduced by plastic sheets while monitoring spectral behavior of covered vineyards

Estudio de caso: Propulsora Siderúrgica, un conflicto sindical en los años setenta

La ponencia explora el proceso de organización gremial y las prácticas políticas que desarrollaron los trabajadores de la fábrica Propulsora Siderúrgica en el transcurso de la contienda sindical. La misma transcurrió entre el mes de mayo y septiembre del año 1974. La empresa formaba parte de las nuevas companías de tipo “desarrollistas”: era productora siderúrgica y propiedad del grupo Techint. Estaba situada en la ciudad de Ensenada perteneciente al área del Gran La Plata. Se busca rastrear las experiencias de organización, las condiciones laborales, la relación que mantuvieron los trabajadores con el gobierno y con la conducción de la Unión Obrera Metalúrgica (UOM). Asimismo, se examinan las formas de democracia sindical que establecieron durante el conflicto sindical, sus demandas y su vinculación con las organizaciones políticas de la “Nueva Izquierda”.Jornadas realizadas junto con el I Encuentro Latinoamericano de Metodología de las Ciencias Sociales.Facultad de Humanidades y Ciencias de la Educació