Marine Antimicrobial Peptides: A Promising Source of New Generation Antibiotics and Other Bio-active Molecules

International Journal of Peptide Research and Therapeutics - Multidrug resistant pathogenic microorganisms have created a global health crisis. This resistance emerged due to the improper use of...     

Bacterial NHEJ: a never ending story

Double‐strand breaks (DSBs) are the most detrimental DNA damage encountered by bacterial cells. DBSs can be repaired by homologous recombination thanks to the availability of an intact DNA template or by Non‐Homologous End Joining (NHEJ) when no intact template is available. Bacterial NHEJ is performed by sets of proteins of growing complexity from Bacillus subtilis and Mycobacterium tuberculosis to Streptomyces and Sinorhizobium meliloti. Here, we discuss the contribution of these models to the understanding of the bacterial NHEJ repair mechanism as well as the involvement of NHEJ partners in other DNA repair pathways. The importance of NHEJ and of its complexity is discussed in the perspective of regulation through the biological cycle of the bacteria and in response to environmental stimuli. Finally, we consider the role of NHEJ in genome evolution, notably in horizontal gene transfer.     

Physcomitrella patens Reute mCherry as a tool for efficient crossing within and between ecotypes

• Physcomitrella patens is a monoecious moss that is predominantly selfing in the wild. Laboratory crossing techniques have been established and crosses between the sequenced Gransden ecotype and the genetically divergent Villersexel ecotype were used for genetic mapping. The recently introduced ecotype Reute has a high fertility rate and is genetically more closely related to the Gransden ecotype than the Villersexel ecotype. Reute sexual reproduction phenology is similar to Gransden, which should allow successful crossing.
• Using the Reute ecotype and an existing Gransden mutant as a test case, we applied a normalised crossing approach to demonstrate crossing potential between these ecotypes. Also, using a standard transformation approach, we generated Reute fluorescent strains expressing mCherry that allow an easy detection of crossed offspring (sporophyte).
• We show that Reute can be successfully crossed with a self‐infertile DR5:DsRed2 mutant generated in the Gransden background. Using newly established Reute fluorescent strains, we show that they can efficiently fertilise Reute as well as Gransden wild type. The resulting progeny display Mendelian 1:1 segregation of the fluorescent marker(s), demonstrating the suitability of such strains for genetic crossing.
• Overall our results demonstrate that Reute is highly suitable for genetic crossing. The Reute mCherry strain can be used as a suitable background for offspring selection after crossing.

     

Label‐free multi‐parametric imaging of single cells: dual picosecond optoacoustic microscopy

Advances in microscopy with new visualization possibilities often bring dramatic progress to our understanding of the intriguing cellular machinery. Picosecond optoacoustic micro‐spectroscopy is an optical technique based on ultrafast pump‐probe generation and detection of hypersound on time durations of picoseconds and length scales of nanometers. It is experiencing a renaissance as a versatile imaging tool for cell biology research after a plethora of applications in solid‐state physics. In this emerging context, this work reports on a dual‐probe architecture to carry out real‐time parallel detection of the hypersound propagation inside a cell that is cultured on a metallic substrate, and of the hypersound reflection at the metal/cell adhesion interface. Using this optoacoustic modality, several biophysical properties of the cell can be measured in a noncontact and label‐free manner. Its abilities are demonstrated with the multiple imaging of a mitotic macrophage‐like cell in a single run experiment.      

Pollinator parasites and the evolution of floral traits

The main selective force driving floral evolution and diversity is plant–pollinator interactions. Pollinators use floral signals and indirect cues to assess flower reward, and the ensuing flower choice has major implications for plant fitness. While many pollinator behaviors have been described, the impact of parasites on pollinator foraging decisions and plant–pollinator interactions have been largely overlooked. Growing evidence of the transmission of parasites through the shared‐use of flowers by pollinators demonstrate the importance of behavioral immunity (altered behaviors that enhance parasite resistance) to pollinator health. During foraging bouts, pollinators can protect themselves against parasites through self‐medication, disease avoidance, and grooming. Recent studies have documented immune behaviors in foraging pollinators, as well as the impacts of such behaviors on flower visitation. Because pollinator parasites can affect flower choice and pollen dispersal, they may ultimately impact flower fitness. Here, we discuss how pollinator immune behaviors and floral traits may affect the presence and transmission of pollinator parasites, as well as how pollinator parasites, through these immune behaviors, can impact plant–pollinator interactions. We further discuss how pollinator immune behaviors can impact plant fitness, and how floral traits may adapt to optimize plant fitness in response to pollinator parasites. We propose future research directions to assess the role of pollinator parasites in plant–pollinator interactions and evolution, and we propose better integration of the role of pollinator parasites into research related to pollinator optimal foraging theory, floral diversity and agricultural practices.     

FXR-deficiency confers increased susceptibility to torpor

The role of the nuclear receptor FXR in adaptive thermogenesis was investigated using FXR-deficient mice. Despite elevated serum bile acid concentrations and increased mRNA expression profiles of thermogenic genes in brown adipose tissue, FXR-deficiency did not alter energy expenditure under basal conditions. However, FXR-deficiency accelerated the fasting-induced entry into torpor in a leptin-dependent manner. FXR-deficient mice were also extremely cold-intolerant. These altered responses may be linked to a more rapid decrease in plasma concentrations of metabolic fuels (glucose, triglycerides) thus impairing uncoupling protein 1-driven thermogenesis. These results identify FXR as a modulator of energy homeostasis.     

Bacterial expression, NMR, and electrophysiology analysis of chimeric short/long-chain alpha-neurotoxins acting on neuronal nicotinic receptors

Different snake venom neurotoxins block distinct subtypes of nicotinic acetylcholine receptors (nAChR). Short-chain alpha-neurotoxins preferentially inhibit muscle-type nAChRs, whereas long-chain alpha-neurotoxins block both muscle-type and alpha7 homooligomeric neuronal nAChRs. An additional disulfide in the central loop of alpha- and kappa-neurotoxins is essential for their action on the alpha7 and alpha3beta2 nAChRs, respectively. Design of novel toxins may help to better understand their subtype specificity. To address this problem, two chimeric toxins were produced by bacterial expression, a short-chain neurotoxin II Naja oxiana with the grafted disulfide-containing loop from long-chain neurotoxin I from N. oxiana, while a second chimera contained an additional A29K mutation, the most pronounced difference in the central loop tip between long-chain alpha-neurotoxins and kappa-neurotoxins. The correct folding and structural stability for both chimeras were shown by (1)H and (1)H-(15)N NMR spectroscopy. Electrophysiology experiments on the nAChRs expressed in Xenopus oocytes revealed that the first chimera and neurotoxin I blockalpha7 nAChRs with similar potency (IC(50) 6.1 and 34 nM, respectively). Therefore, the disulfide-confined loop endows neurotoxin II with full activity of long-chain alpha-neurotoxin and the C-terminal tail in neurotoxin I is not essential for binding. The A29K mutation of the chimera considerably diminished the affinity for alpha7 nAChR (IC(50) 126 nM) but did not convey activity at alpha3beta2 nAChRs. Docking of both chimeras toalpha7 andalpha3beta2 nAChRs was possible, but complexes with the latter were not stable at molecular dynamics simulations. Apparently, some other residues and dimeric organization of kappa-neurotoxins underlie their selectivity for alpha3beta2 nAChRs.     

Energetic reserves, leptin and testosterone: a refinement of the immunocompetence handicap hypothesis

The immunocompetence handicap hypothesis (ICHH) assumes that testosterone (T), required for the expression of sexual traits, can also incur a cost due to its immunosuppressive properties. However, T-dependent immunosuppression could also arise as an indirect consequence of energy reallocation from the immune system to other metabolic demands. Leptin is mostly produced in lipogenic tissues and its circulating level is positively correlated with the amount of lipid reserves. Leptin also has an important role as immunoenhancer and we suggest that this hormone could play a role as a mediator of the immunosuppressive effect of testosterone. In particular, we propose that only the individuals able to maintain large lipid reserves (with high leptin levels), while sustaining high testosterone levels, might be able to develop sexual displays without an impairment of their immune defences. Here, we tested one of the assumptions underlying this extension of the ICHH: leptin administration should attenuate testosterone-induced immunosuppression. T-implanted and control male zebra finches (Taeniopygia guttata) received daily injections of leptin or phosphate buffered saline. T-implants initially depressed the phytohaemagglutinin-induced immune response. However, T-birds injected with leptin enhanced their immune response to the level of control birds. These results open a new perspective on the study of the ICHH.