Development of Lectin directed Theranostics against Pseudomonas aeruginosa

The gram-negative bacterium Pseudomonas aeruginosa is one of the major causes of hospital-acquired infections and a leading cause of death in cystic fibrosis patients. Rapid emergence of multidrug resistant strains calls for urgent development of novel treatment options. In this work, P. aeruginosa carbohydrate binding proteins LecA and LecB were explored as extracellular targets for lectin-directed theranostics. LecA and LecB ligands were synthetically modified to allow conjugation to imaging moieties in order to enable the detection of an infection site. Fluorescein-carbohydrate conjugates showed good affinities to LecA and LecB and were used to stain P. aeruginosa biofilm aggregates in vitro. Furthermore, rapidly accessible divalent LecA ligands were designed and synthesised and low nanomolar affinities were achieved. Optimization of these divalent ligands yielded highly potent LecA inhibitors with excellent solubility and good ADME properties in vitro. Finally, this design of divalent LecA inhibitors allowed the development of highly potent LecA-targeting imaging probes.Das Gram-negative Bakterium Pseudomonas aeruginosa ist mit hauptverantwortlich für Krankenhausinfektionen und eine der Haupttodesursachen für Patienten mit zystischer Fibrose. Das vermehrte Aufkommen multiresistenter Keime fordert dringend die Erforschung neuartiger Therapiestrategien. In dieser Arbeit wurden zwei Kohlenhydrat-bindende Proteine von P. aeruginosa, LecA und LecB, als extrazelluläre Zielstrukturen für neuartige Lektinbindende Theranostika erforscht. Liganden von LecA und LecB wurden synthetisch so modifiziert, dass eine Konjugation mit Fluoreszenzfarbstoffen die Erkennung von Infektionsherden ermöglichen soll. Diese Fluorescein-Kohlenhydrat-Konjugate zeigten gute Affinitäten gegenüber LecA und LecB und wurden verwendet um Biofilm-Aggregate von P. aeruginosa in vitro zu färben. Weiterhin konnten schnell zugängliche divalente LecA-Liganden mit niedrig nanomolaren Affinitäten designt und synthetisiert werden. Weitere Optimierungen dieser Verbindungen ergaben hochpotente LecA-Inhibitoren mit exzellenter Löslichkeit und guten ADME-Parametern in vitro. Schließlich ermöglichten diese divalenten LecA-Inhibitoren die Entwicklung hochpotenter LecA-spezifischer Kontrastmittel

Latimerija - živi fosil

This study, which derives from work initiated as part of a N.A.T.O. Collaborative Linkage Grant (LST‐CLG No. 979499), supported by consecutive research contracts (SF0238 and SF0248) from the UK Department of Environment, Food and Rural Affairs (to GHC), which were complemented by a Marie Curie postdoctoral fellowship (PIEF‐GA‐2008‐219707) and a subsequent research grant from the National Science Centre, Poland (decision No DEC‐2011/01/D/NZ8/01807) to GZ.Carotenoid‐based pigmentation is a striking feature of many taxa, yet the function, if any, of colour traits is often unclear. Pumpkinseed Lepomis gibbosus, a widely introduced freshwater sunfish that exhibits alternative male mating strategies, express a striking, red operculum spot. To investigate the potential function of this red spot as a signal in this species' mating system, we determined the presence and measured the size of red operculum spots in fish collected from 12 populations in five European countries in which pumpkinseed is an established non‐native species. We subsequently related the presence and size of the red spot to body size and mating strategy, based on an analysis of relative gonad size (gonado‐somatic index, GSI), using a mixed modelling approach. The study demonstrated that the presence of a red operculum spot in pumpkinseed is associated with sexual maturation, with GSI frequency distributions suggesting that cuckolders in some non‐native populations comprised both sneaker and satellite males, the latter not having previously been reported for this species. Further, the size of red spot correlated strongly with body size in parental and cuckolder males, although there was no difference in the presence or size of the red operculum spot between male mating strategies. The function of a red operculum spot in females is not clear but may be partly mediated by pleiotropic genetic mechanisms. Red operculum spots appear to function as signals of male maturation and body size in pumpkinseed, irrespective of mating strategy.PostprintPeer reviewe

Native drivers of fish life history traits are lost during the invasion process

Rapid adaptation to global change can counter vulnerability of species to population declines and extinction. Theoretically, under such circumstances both genetic variation and phenotypic plasticity can maintain population fitness, but empirical support for this is currently limited. Here, we aim to characterize the role of environmental and genetic diversity, and their prior evolutionary history (via haplogroup profiles) in shaping patterns of life history traits during biological invasion. Data were derived from both genetic and life history traits including a morphological analysis of 29 native and invasive populations of topmouth gudgeon Pseudorasbora parva coupled with climatic variables from each location. General additive models were constructed to explain distribution of somatic growth rate (SGR) data across native and invasive ranges, with model selection performed using Akaike's information criteria. Genetic and environmental drivers that structured the life history of populations in their native range were less influential in their invasive populations. For some vertebrates at least, fitness-related trait shifts do not seem to be dependent on the level of genetic diversity or haplogroup makeup of the initial introduced propagule, nor of the availability of local environmental conditions being similar to those experienced in their native range. As long as local conditions are not beyond the species physiological threshold, its local establishment and invasive potential are likely to be determined by local drivers, such as density-dependent effects linked to resource availability or to local biotic resistance

Does latitude drive the phenotypic plasticity of morphological traits in non-native pumpkinseed populations from Europe?

Phenotypic plasticity is one of the traits often associated with successful invasive species, providing each individual with a unique ability to adapt to novel environments. The aim of the present study was to evaluate the morphological plasticity of Lepomis gibbosus, a successful invader outside of its native North American range, across the latitudinal extent of the species' introduced European range to determine whether or not climate, using latitude as a surrogate of thermal conditions, has an underlying influence on the species' morphology and consequently its invasiveness potential. Five characters (body depth, dorsal, ventral and pelvic fins, and eye diameter) differed significantly among the populations, and in particular the Slovakian population, with a significant effect of latitude on five other characters (maxilla length, pre-dorsal, pre-ventral, pre-orbital distances, and caudal peduncle length), which distinguished the various populations and distinguished the Portuguese population from the rest. The results suggest considerable morphological plasticity in L. gibbosus, with two different patterns of development that can reflect to different allocation of sources as well as different stage of invasion process

Red operculum spots, body size, maturation and evidence for a satellite male phenotype in non-native European populations of pumpkinseed <i>Lepomis gibbosus</i>

Carotenoid‐based pigmentation is a striking feature of many taxa, yet the function, if any, of colour traits is often unclear. Pumpkinseed Lepomis gibbosus, a widely introduced freshwater sunfish that exhibits alternative male mating strategies, express a striking, red operculum spot. To investigate the potential function of this red spot as a signal in this species' mating system, we determined the presence and measured the size of red operculum spots in fish collected from 12 populations in five European countries in which pumpkinseed is an established non‐native species. We subsequently related the presence and size of the red spot to body size and mating strategy, based on an analysis of relative gonad size (gonado‐somatic index, GSI), using a mixed modelling approach. The study demonstrated that the presence of a red operculum spot in pumpkinseed is associated with sexual maturation, with GSI frequency distributions suggesting that cuckolders in some non‐native populations comprised both sneaker and satellite males, the latter not having previously been reported for this species. Further, the size of red spot correlated strongly with body size in parental and cuckolder males, although there was no difference in the presence or size of the red operculum spot between male mating strategies. The function of a red operculum spot in females is not clear but may be partly mediated by pleiotropic genetic mechanisms. Red operculum spots appear to function as signals of male maturation and body size in pumpkinseed, irrespective of mating strategy

Native drivers of fish life history traits are lost during the invasion process

Rapid adaptation to global change can counter vulnerability of species to population declines and extinction. Theoretically, under such circumstances both genetic variation and phenotypic plasticity can maintain population fitness, but empirical support for this is currently limited. Here, we aim to characterize the role of environmental and genetic diversity, and their prior evolutionary history (via haplogroup profiles) in shaping patterns of life history traits during biological invasion. Data were derived from both genetic and life history traits including a morphological analysis of 29 native and invasive populations of topmouth gudgeon Pseudorasbora parva coupled with climatic variables from each location. General additive models were constructed to explain distribution of somatic growth rate (SGR) data across native and invasive ranges, with model selection performed using Akaike's information criteria. Genetic and environmental drivers that structured the life history of populations in their native range were less influential in their invasive populations. For some vertebrates at least, fitness-related trait shifts do not seem to be dependent on the level of genetic diversity or haplogroup makeup of the initial introduced propagule, nor of the availability of local environmental conditions being similar to those experienced in their native range. As long as local conditions are not beyond the species physiological threshold, its local establishment and invasive potential are likely to be determined by local drivers, such as density-dependent effects linked to resource availability or to local biotic resistance

Life-history traits and potential invasiveness of introduced pumpkinseed Lepomis gibbonus populations in northwestern Europe

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