Species-dependent Manner Research Articles

Metformin alleviates lead-induced mitochondrial fragmentation via AMPK/Nrf2 activation in SH-SY5Y cells

As a widely acknowledged environmental pollutant, lead (Pb) exhibits neurological toxicity primarily due to the vulnerability of neural system. It is suggested that Pb could perturb mitochondrial function, triggering the following disturbance of cellular homeostasis. Here, we focused on the role of mitochondrial dynamics in Pb-induced cell damage. Pb exposure enhanced mitochondrial fragmentation and elevated p-Drp1 (s616) level in a reactive oxygen species (ROS) dependent manner, leading to cell death and energy shortage. By applying metformin, an AMP-activated protein kinase (AMPK) activator, these impairments could be alleviated via activation of AMPK, validated by experiments of pharmacological inhibition of AMPK. Further investigation confirmed that nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor managing antioxidative function, and its downstream antioxidant detoxifying enzyme were activated by metformin, resulting in the inhibition of the Pb-caused oxidative stress. Moreover, Nrf2 mediated the protection of metformin against mitochondrial fragmentation induced by Pb exposure, while knockdown of Nrf2 abrogated the protective effect. Finally, the treatment of Mdivi-1, a mitochondrial fission inhibitor, reversed Pb-triggered cell death, revealing that excessive mitochondrial fission is detrimental. To conclude, metformin could ameliorate Pb-induced mitochondrial fragmentation via antioxidative effects originated from AMPK/Nrf2 pathway activation, promoting energy supply and cell survival.

Bio-Herbicidal Potential of the Essential Oils from Different Rosmarinus officinalis L. Chemotypes in Laboratory Assays

The current study aimed to assess the allelopathic effect of Rosmarinus officinalis L. essential oils (EOs) to define the potent effect against weed species, by exploring distinct chemotypes and their main compounds. The EOs from eight accessions were characterized. Their components were identified by gas chromatography, and four chemotypes were defined; C1 (α-pinene), C2 (camphor), C3 (α-pinene/1,8-cineole), and C4 (α-pinene/1,8-cineole/camphor). Four concentrations of the EOs (400, 800, 1200, and 2400 μL/L) and the main compounds of each chemotype were tested in a laboratory assay against Amaranthus retroflexus L. and Lolium perenne L. in pre- and post-germination. The results showed that the EOs significantly affected all the tested parameters (germination, early growth, and physiological and histological parameters of the weeds under study) in a dose, chemotype, and species dependent manner. A. retroflexus was more sensitive than L. perenne at germination level being significantly inhibited at the lowest dose of all the chemotypes. The latter all exhibited significant effects but with a higher potency of C2 (camphor chemotype) and C3 (α-pinene/1,8-cineole chemotype), as well qualitative differences in the induced damage. Our results thus increase knowledge about the role of the monoterpene composition in bio-herbicidal effect, which can help in the development of EO based bio-herbicides.

Saccharin Supplementation Inhibits Bacterial Growth and Reduces Experimental Colitis in Mice.

Non-caloric artificial sweeteners are frequently discussed as components of the “Western diet”, negatively modulating intestinal homeostasis. Since the artificial sweetener saccharin is known to depict bacteriostatic and microbiome-modulating properties, we hypothesized oral saccharin intake to influence intestinal inflammation and aimed at delineating its effect on acute and chronic colitis activity in mice. In vitro, different bacterial strains were grown in the presence or absence of saccharin. Mice were supplemented with saccharin before or after induction of acute or chronic colitis using dextran sodium sulfate (DSS) and the extent of colitis was assessed. Ex vivo, intestinal inflammation, fecal bacterial load and composition were studied by immunohistochemistry analyses, quantitative PCR, 16 S RNA PCR or next generation sequencing in samples collected from analyzed mice. In vitro, saccharin inhibited bacterial growth in a species-dependent manner. In vivo, oral saccharin intake reduced fecal bacterial load and altered microbiome composition, while the intestinal barrier was not obviously affected. Of note, DSS-induced colitis activity was significantly improved in mice after therapeutic or prophylactic treatment with saccharin. Together, this study demonstrates that oral saccharin intake decreases intestinal bacteria count and hence encompasses the capacity to reduce acute and chronic colitis activity in mice.

Pan-cancer analysis reveals synergistic effects of CDK4/6i and PARPi combination treatment in RB-proficient and RB-deficient breast cancer cells

DNA damage results in mutations and plays critical roles in cancer development, progression, and treatment. Targeting DNA damage response in cancers by inhibiting poly-(ADP-ribose) polymerases (PARPs) offers an important therapeutic strategy. However, the failure of PARP inhibitors to markedly benefit patients suggests the necessity for developing new strategies to improve their efficacy. Here, we show that the expression of cyclin-dependent kinase 4/6 (CDK4/6) complex members significantly correlates with mutations (as proxies of DNA damages), and that the combination of CDK4/6 and PARP inhibitors shows synergy in both RB-proficient and RB-deficient breast cancer cells. As PARPs constitute sensors of DNA damage and are broadly involved in multiple DNA repair pathways, we hypothesized that the combined inhibition of PARPs and DNA repair (or repair-related) pathways critical for cancer (DRPCC) should show synergy. To identify druggable candidate DRPCC(s), we analyzed the correlation between the genome-wide expression of individual genes and the mutations for 27 different cancer types, assessing 7146 exomes and over 1,500,000 somatic mutations. Pathway enrichment analyses of the top-ranked genes correlated with mutations indicated “cell cycle pathway” as the top candidate DRPCC. Additionally, among functional cell-cycle complexes, the CDK4/6 complex showed the most significant negative correlation with mutations, also suggesting that combined CDK4/6 and PARP inhibition might exhibit synergy. Furthermore, combination treatment showed synergy in not only RB-proficient but also RB-deficient breast cancer cells in a reactive oxygen species-dependent manner. These findings suggest a potential therapeutic strategy to improve the efficacy of PARP and CDK4/6 inhibitors in cancer treatment.

Inhibitory activity of biofunctionalized silver-capped N-methylated water-soluble chitosan thiomer for microbial and biofilm infections

One of the most important self-defense strategies employed by bacteria to resist the action of antibiotics is a biofilm formation upon the infected surface. Thus, there is an urgent need to explore novel candidates that have potent antibacterial and anti-biofilm effects to tackle this challenge. In this endeavor, we have transformed shrimp shell wastes to N-methylated water-soluble chitosan thiomer (MWSCT) which was used as either a chelating agent or bio-reductant and capping agent for Ag(I) ions in the preparation of a Ag(I)MWSCT complex or silver nanocomposite (Ag(0)MWSCT), for targeting antibacterial and anti-biofilm applications. The antibacterial and anti-biofilm performance of the new methylated chitosan thiomer (MWSCT) and its silver architectures (Ag(I)MWSCT, Ag(0)MWSCT) were assessed in vitro against E. coli and S. aureus. These new materials have significant capacities to synergistically inhibit the proliferation of the targeted bacterial cells and biofilm formation, in a structure- and species-dependent manner. Ag(0)MWSCT emerged as the most potent compound in inhibiting the growth of bacterial strains (MICE. coli/ MICS. aureus = 0.05/ 0.34 μg/mL, 1.6-/ 2.5-times lower than that recorded for the clinical drug (ciprofloxacin, Cipro). Also, this nanocomposite showed the highest anti-biofilm effects (only 1.7% E. coli biofilm growth; 11.8% staphylococcal biofilm growth).

Imaging studies of bacterial biofilms on cochlear implants-Bioactive glass (BAG) inhibits mature biofilm.

The capability of Pseudomonas aeruginosa and Staphylococcus aureus to form biofilm on varying CI component materials differs in the presence and absence of bioactive glass (BAG). The application of BAG induces significant changes in biofilm morphology which can be visualized via scanning electron microscopy (SEM). Bacterial biofilm formation on medical devices, such as cochlear implants (CI), can lead to chronic infections. Interestingly, BAG of type S53P4 seems to be a promising tool for use in the reduction of biofilm development. Primarily, four bacterial species known to cause implant-related infections, P.aeruginosa (ATCC9027), S. aureus (ATCC6538), Staphylococcus epidermidis (ATCC12228) and Streptococcus pyogenes (ATCC19615) were analyzed regarding their capacity to form biofilm on CI components manufactured from three kinds of material: silicone, platinum and titanium. Subsequently, P. aeruginosa and S. aureus biofilms were visualized using scanning electron microscopy, comparing BAG-treated biofilm with non-treated biofilm. The four bacterial species presented biofilm-forming capabilities in a species and surface dependent manner. Metal CI components allowed for the greatest proliferation of biofilm. S. aureus and P. aeruginosa showed the highest rate of biofilm formation on polystyrene surfaces. For both species, SEM revealed altered biofilm morphology after treatment of S53P4 BAG. This study indicates that bacterial biofilm formation and structure on CI components is dependent on the surface composition, altering between metal and silicone surfaces. After application of BAG, changes in biofilm morphology on CI components were observed. These data highlight the impact of BAG on bacterial biofilm morphology.

Sialylated O -Glycans from Hen Egg White Ovomucin are Decomposed by Mucin-degrading Gut Microbes.

Ovomucin, a hen egg white protein, is characterized by its hydrogel-forming properties, high molecular weight, and extensive O -glycosylation with a high degree of sialylation. As a commonly used food ingredient, we explored whether ovomucin has an effect on the gut microbiota. O- Glycan analysis revealed that ovomucin contained core-1 and 2 structures with heavy modification by N -acetylneuraminic acid and/or sulfate groups. Of the two mucin-degrading gut microbes we tested, Akkermansia muciniphila grew in medium containing ovomucin as a sole carbon source during a 24 h culture period, whereas Bifidobacterium bifidum did not. Both gut microbes, however, degraded ovomucin O -glycans and released monosaccharides into the culture supernatants in a species-dependent manner, as revealed by semi-quantified mass spectrometric analysis and anion exchange chromatography analysis. Our data suggest that ovomucin potentially affects the gut microbiota through O -glycan decomposition by gut microbes and degradant sugar sharing within the community.

Selenium nanoparticles reduce glucose metabolism and promote apoptosis of glioma cells through reactive oxygen species-dependent manner.

Gliomas are the most common, malignant, and lethal tumors in adults. Furthermore, gliomas are highly resistant to current chemotherapeutic drugs. Thus, new effective anticancer drugs for glioma are urgently needed. Selenium nanoparticles have been reported to have potent anti-tumor activity, although the specific mechanism is not fully understood. This study aimed to test the anti-tumor effect of selenium nanoparticles and its mechanism. We used selenium nanoparticles to treat commercial glioma cell lines, and patient-derived glioma cells, and then used the MTT assay to determine selenium nanoparticles effect against these. Apoptotic cell death was determined by annexin V-Fluos staining kit. Glucose uptake, lactate, and adenosine triphosphate production, together with hexokinase 2 and pyruvate kinase activities were measured to determine the glucose metabolism level. Reactive oxygen species production was tested using 2',7'-dichlorodihydrofluorescein diacetate. Our results showed that selenium nanoparticles had a potent cytotoxic effect in glioma cells, regardless of whether they were drug-resistant or not, whereas it showed less toxic effect in normal healthy cells. Further tests showed that selenium nanoparticles treatment leads to apoptotic cell death enhancement and glucose metabolism reduction, and this process was in a reactive oxygen species pathway-dependent manner. These results may provide a novel direction for glioma therapy in the future.

Modulation of above-belowground plant-herbivore interactions by entomopathogenic nematodes

Plants indirectly mediate above-belowground interactions between root- and shoot- herbivores via changes in primary and secondary metabolism. Such effects can cascade up to affect higher trophic level organisms such as predators, however, to what extent predators can in turn influence plant-mediated above-belowground interactions needs to be further elucidated. In this study, we examined the effect of entomopathogenic nematodes (EPNs) (Heterorhabditis bacteriophora and Steinernema carpocapsae) on the interactions between a belowground herbivore, the root-knot nematode (RKN) Meloidogyne arenaria, and an aboveground herbivore, the green-peach aphid Myzus persicae on tobacco (Nicotiana tabacum) plants. We found that the effect of RKNs on aphid population growth and reproduction was negative only when EPNs were inoculated near the rhizosphere. We also observed that the addition of EPNs in the rhizosphere annihilated the positive effect of the aphids on the RKNs feeding on tobacco roots. While aphids and RKNs feeding, respectively, reduced the root and shoot biomass independently of EPNs presence in the rhizosphere, the concentration of glucose and nicotine in tobacco leaves was modified by the presence of EPNs in a species-dependent manner. Our study reveals that tobacco plants detect the presence of EPNs in the rhizosphere and in turn they respond by modifying their interactions with the above- and belowground herbivores. Therefore, soil-dwelling organisms that are not directly associated with the plants can also have community-wide effects that are mediated by changes in plant primary and secondary chemistry.

Formulation of a triple combination gemcitabine plus romidepsin + cisplatin regimen to efficaciously and safely control triple-negative breast cancer tumor development.

Triple-negative breast cancer (TNBC) is an aggressive, lethal, and heterogeneous subtype of breast cancers, tending to have lower 5-year survival rates than other BC subtypes in response to conventional chemotherapies. This study's aim was to identify advanced regimens to effectively control TNBC tumor development. We investigated the combination of the DNA synthesis inhibitor gemcitabine, the DNA-damaging agent cisplatin, and the histone deacetylase inhibitor romidepsin to control a variety of breast cells in vitro. We studied the toxicity of drug doses and administration schedules to determine tolerable combination regimens in immune-deficient nude and -competent BALB/c mice. We then studied the efficacy of tolerable regimens in controlling TNBC cell-derived xenograft development in nude mice. By reducing clinically equivalent doses of each agent in combination, we formulated tolerable regimens in animals. We verified that the tolerable triple combination gemcitabine plus romidepsin + cisplatin regimen more efficacious than double combination regimens in controlling xenograft tumor development in nude mice. A triple combination of gemcitabine + romidepsin + cisplatin synergistically induced death of the TNBC M.D. Anderson-Metastatic Breast cancer (MDA-MB) 231 and MDA-MB468, as well as Michigan Cancer Foundation (MCF) 7, MCF10A, and MCF10A-Ras cells. Cell death induced by gemcitabine + romidepsin + cisplatin was in a reactive oxygen species-dependent manner. Considering the high costs for developing a new anticancer agent, we used the FDA-approved drugs gemcitabine, romidepsin (is approved for T-cell lymphoma and is under clinical trial for TNBC), and cisplatin to economically formulate an efficacious and safe combination regimen. The highly efficacious gemcitabine plus romidepsin + cisplatin regimen should be poised for efficient translation into clinical trials, ultimately contributing to reduced mortality and improved quality of life for TNBC patients.

The influence of climate change related factors on the response of two clam species to diclofenac.

Diclofenac (DIC) is one of the non-steroidal anti-inflammatory drugs (NSAID) with higher consumption rates, used in both human and veterinary medicine. Previous studies already demonstrated the presence of this drug in aquatic environments and adverse effects towards inhabiting organisms. However, with the predictions of ocean acidification and warming, the impacts induced by DIC may differ from what is presently known and can be species-dependent. Thus, the present study aimed to comparatively assess the effects caused by DIC in the clams Ruditapes philippinarum and Ruditapes decussatus and evaluate if these impacts were influenced by pH and temperature. For this, organisms were acclimated for 30 days at two different temperature and pH (control conditions: pH 8.1, 17 °C; climate change forecasted scenario: pH 7.7, 20 °C) in the absence of drugs (experimental period I) followed by 7 days exposure under the same water physical parameters but in absence or presence of the pharmaceutical drug (at 1 μg/L, experimental period II). Biochemical responses covering metabolic capacity, oxidative stress and damage-related biomarkers were contrasted in clams at the end of the second experimental period. The results showed that under actual conditions, R. philippinarum individuals exposed to DIC presented enhanced antioxidant activities and reduced their respiration rate compared with non-contaminated clams. When exposed to the predicted climate change conditions, a similar response was observed in contaminated clams, but in this case clams increased their metabolic activities probably to fight the stress caused by the combination of both stressors. When R. decussatus was exposed to DIC, even at actual pH and temperature conditions, their antioxidant defences were also elevated but their baseline enzymatic activities were also naturally higher in respect to R. philippinarum. Although clams may use different strategies to prevent DIC damage, both clam species showed under low pH and high temperature limited oxidative stress impacts in line with a lower DIC bioaccumulation. The present findings reveal that predicted climate change related factors may not enhance the impacts of DIC in Ruditapes clams in a species-dependent manner although both displayed particular mechanisms to face stress.

Pig liver esterases PLE1 and PLE6: heterologous expression, hydrolysis of common antibiotics and pharmacological consequences

Carboxylesterases, historically referred as non-specific esterases, are ubiquitous hydrolases with high catalytic efficiency. Without exceptions, all mammalian species studied contain multiple forms of carboxylesterases. While having been widely studied in humans and experimental animals, these enzymes remain to be characterized in farm animals. In this study, we showed that pig liver esterase 1 (PLE1) and pig liver esterase 6 (PLE6) were highly active toward amoxicillin (AMO) and ampicillin (AMP), two major antibiotics that are widely used in food-supplements. Mass-spectrometric analysis established that the hydrolysis occurred at the β-lactam amide bond and the hydrolysis drastically decreased or completely eliminated the antibacterial activity. Furthermore, hydrolytic activity and proteomic analysis suggested that trace PLEs existed in pig plasma and contributed little to the hydrolysis of AMO and AMP. These results suggested that carboxylesterases-based hydrolysis determines the therapeutic intensity of these and related antibiotics and the magnitude of the determination occurs in a species-dependent manner.

Neurotensin receptors regulate transactivation of the EGFR and HER2 in a reactive oxygen species-dependent manner

Neurotensin is a 13 amino acid peptide which is present in many lung cancer cell lines. Neurotensin binds with high affinity to the neurotensin receptor 1, and functions as an autocrine growth factor in lung cancer cells. Neurotensin increases tyrosine phosphorylation of the epidermal growth factor receptor (EGFR) and the neurotensin receptor 1 antagonist SR48692 blocks the transactivation of the EGFR. Here the effects of reactive oxygen species on the transactivation of the EGFR and HER2 were investigated. Using non-small cell lung cancer (NSCLC) cell lines, neurotensin receptor 1 mRNA and protein were present. Using NCI–H838 cells, neurotensin or neurotensin8−13 but not neurotensin1−8 increased EGFR, ERK and HER2 tyrosine phosphorylation which was blocked by SR48692. Neurotensin addition to NCI–H838 cells increased significantly reactive oxygen species which was inhibited by SR48692, Tiron (superoxide scavenger) and diphenylene iodonium (DPI inhibits the ability of NADPH oxidase and dual oxidase enzymes to produce reactive oxygen species). Tiron or DPI impaired the ability of neurotensin to increase EGFR, ERK and HER2 tyrosine phosphorylation. Neurotensin stimulated NSCLC cellular proliferation whereas the growth was inhibited by SR48692, DPI or lapatinib (lapatinib is tyrosine kinase inhibitor of the EGFR and HER2). Lapatinib inhibited the ability of the neurotensin receptor 1 to transactivate the EGFR and HER2. The results indicate that neurotensin receptor 1 regulates the transactivation of the EGFR and HER2 in a reactive oxygen species-dependent manner.

Mercury resistance and bioremediation mediated by endophytic fungi

The present study proposes the use of endophytic fungi for mercury bioremediation in in vitro and host-associated systems. We examined mercury resistance in 32 strains of endophytic fungi grown in culture medium supplemented with toxic metal concentrations. The residual mercury concentrations were quantified after mycelial growth. Aspergillus sp. A31, Curvularia geniculata P1, Lindgomycetaceae P87, and Westerdykella sp. P71 were selected and further tested for mercury bioremediation and bioaccumulation in vitro, as well as for growth promotion of Aeschynomene fluminensis and Zea mays in the presence or absence of the metal. Aspergillus sp. A31, C. geniculata P1, Lindgomycetaceae P87 and Westerdykella sp. P71 removed up to 100% of mercury from the culture medium in a species-dependent manner and they promoted A. fluminensis and Z. mays growth in substrates containing mercury or not (Dunnett's test, p < 0.05). Lindgomycetaceae P87 and C. geniculata P1 are dark septate endophytic fungi that endophytically colonize root cells of their host plants. The increase of host biomass correlated with the reduction of soil mercury concentration due to the metal bioaccumulation in host tissues and its possible volatilization. The soil mercury concentration was decreased by 7.69% and 57.14% in A. fluminensis plants inoculated with Lindgomycetaceae P87 + Aspergillus sp. A31 and Lindgomycetaceae P87, respectively (Dunnet's test, p < 0.05). The resistance mechanisms of mercury volatilization and bioaccumulation in plant tissues mediated by these endophytic fungi can contribute to bioremediation programs. The biochemical and genetic mechanisms involved in bioaccumulation and volatilization need to be elucidated in the future.

Reconstitution of autophagy ameliorates vascular function and arterial stiffening in spontaneously hypertensive rats.

Insufficient autophagy has been proposed as a mechanism of cellular aging, as this leads to the accumulation of dysfunctional macromolecules and organelles. Premature vascular aging occurs in hypertension. In fact, many factors that contribute to the deterioration of vascular function as we age are accelerated in clinical and experimental hypertension. Previously, we have reported decreased autophagy in arteries from spontaneously hypertensive rats (SHRs); however, the effects of restoring autophagic activity on blood pressure and vascular function are currently unknown. We hypothesized that reconstitution of arterial autophagy in SHRs would decrease blood pressure and improve endothelium-dependent relaxation. We treated 14- to 18-wk-old Wistar rats (n = 7 vehicle and n = 8 trehalose) and SHRs (n = 7/group) with autophagy activator trehalose (2% in drinking water) for 28 days. Blood pressure was measured by radiotelemetry, and vascular function and structure were measured in isolated mesenteric resistance arteries (MRAs) using wire and pressure myographs, respectively. Treatment with trehalose had no effect on blood pressure in SHRs; however, isolated MRAs presented enhanced relaxation to acetylcholine, in a cyclooxygenase- and reactive oxygen species-dependent manner. Similarly, trehalose treatment shifted the relaxation to the Rho kinase (ROCK) inhibitor Y-27632 to the right, indicating reduced ROCK activity. Finally, trehalose treatment decreased arterial stiffness as indicated by the slope of the stress-strain curve. Overall these data indicate that reconstitution of arterial autophagy in SHRs improves endothelial and vascular smooth muscle function, which could synergize to prevent stiffening. As a result, restoration of autophagic activity could be a novel therapeutic for premature vascular aging in hypertension.NEW & NOTEWORTHY This work supports the concept that diminished arterial autophagy contributes to premature vascular aging in hypertension and that therapeutic reconstitution of autophagic activity can ameliorate this phenotype. As vascular age is a new clinically used index for cardiovascular risk, understanding this mechanism may assist in the development of new drugs to prevent premature vascular aging in hypertension.

HIF-1 dependent reversal of cisplatin resistance via anti-oxidative nano selenium for effective cancer therapy

The clinical efficacy of cisplatin (DDP) treatment is largely limited by cisplatin resistance, which is related to the activation of hypoxia-inducible factor 1 (HIF-1). The HIF-1 activation can be induced by low oxygen availability as well as chemotherapeutics in a reactive oxygen species (ROS) dependent manner. Here, instead of the traditional ROS elevation strategy, we designed a chitosan-coated selenium/DDP (CSP) nanoparticle to deplete ROS for circumventing acquired cisplatin resistance. The antioxidative selenium nanoparticles were demonstrated to eliminate cisplatin-induced ROS, and further prevent HIF-1 activation accompanied with cisplatin treatment. A series of cisplatin resistance-associated proteins including glutamate-cysteine ligase modifier subunit (GCLM) and multidrug resistance-associated proteins (MRPs) expression were downregulated in a HIF-1α-dependent manner. And in vitro and in vivo experiments showed that CSP nanoparticles exhibited enhanced antitumor efficacy to cisplatin-resistant A549/DDP lung cancer cell lines and xenografts. These results proved that the side effects of treatment-induced ROS in HIF-1 activation and cisplatin-resistance could be significantly reversed by a selenium nanovehicle, which may possess broader applications in ROS-mediated resistance or other ROS-involved diseases.

Lactobacilli Isolated From Wild Boar (Sus scrofa) Antagonize Mycobacterium bovis Bacille Calmette-Guerin (BCG) in a Species-Dependent Manner.

Background: Wildlife poses a significant burden for the complete eradication of bovine tuberculosis (bTB). In particular, wild boar (Sus scrofa) is one of the most important reservoirs of Mycobacterium bovis, the causal agent of bTB. Wild boar can display from mild TB lesions, usually found in head lymph nodes, to generalized TB lesions distributed in different anatomical regions; but rarely clinical signs, which complicates the diagnosis of Mycobacterium bovis infection and bTB control. Among the possibilities for this variability in lesion distribution is the influence of the host-beneficial commensal-primed immune barrier. In this respect, beneficial microbes may delay bTB dissemination as a consequence of an antagonistic competition for nutrients and phagocytes. In order to explore this possibility, we have tested whether typical commensals such as lactobacilli have the capacity to reduce the survival rate of the surrogate M. bovis strain Bacillus Calmette-Guerin (BCG); and to modulate its phagocyte intake.Results: Three Lactobacillus species, L. casei, L. plantarum, and L. salivarius, isolated from wild boar feces displayed a pH-dependent inhibitory activity against BCG and influenced its intake by porcine blood phagocytes in a species-dependent manner. All lactobacilli showed a very significant bactericidal effect against BCG at low pH, but only isolates of L. plantarum and L. casei displayed such antimycobacterial activity at neutral pH. The genomes of these isolates revealed the presence of two-peptide bacteriocins whose precursor genes up-regulate in the presence of BCG cells. Furthermore, L. plantarum reduced significantly the BCG phagocytic intake, whereas L. casei had the opposite effect. L. salivarius had no significant influence on the phagocytic response to BCG.Conclusions: Our in vitro results show that lactobacilli isolated from wild boar antagonize BCG as a consequence of their antimycobacterial activity and a competitive phagocytic response. These findings suggest that commensal bacteria could play a beneficial role in influencing the outcome of bTB dissemination. Further work with lactobacilli as a potential competitive pressure to control bTB will need to take into account the complex nature of the commensal microbiome, the specific immunity of the wild boar and the in vivo infection context with pathogenic strains of M. bovis.

Species-Specific Biodegradation of Sporopollenin-Based Microcapsules

Sporoderms, the outer layers of plant spores and pollen grains, are some of the most robust biomaterials in nature. In order to evaluate the potential of sporoderms in biomedical applications, we studied the biodegradation in simulated gastrointestinal fluid of sporoderm microcapsules (SDMCs) derived from four different plant species: lycopodium (Lycopodium clavatum L.), camellia (Camellia sinensis L.), cattail (Typha angustifolia L.), and dandelion (Taraxacum officinale L.). Dynamic image particle analysis (DIPA) and field-emission scanning electron microscopy (FE-SEM) were used to investigate the morphological characteristics of the capsules, and Fourier-transform infrared (FTIR) spectroscopy was used to evaluate their chemical properties. We found that SDMCs undergo bulk degradation in a species-dependent manner, with camellia SDMCs undergoing the most extensive degradation, and dandelion and lycopodium SDMCs being the most robust.

Variability in the redox status of plant 2-Cys peroxiredoxins in relation to species and light cycle

Plant 2-Cys peroxiredoxins (2-CysPRXs) are abundant plastidial thiol-peroxidases involved in key signaling processes such as photosynthesis deactivation at night. Their functions rely on the redox status of their two cysteines and on the enzyme quaternary structure, knowledge of which remains poor in plant cells. Using ex vivo and biochemical approaches, we thoroughly characterized the 2-CysPRX dimer/monomer distribution, hyperoxidation level, and thiol content in Arabidopsis, barley, and potato in relation to the light cycle. Our data reveal that the enzyme hyperoxidization level and its distribution as a dimer and monomer vary through the light cycle in a species-dependent manner. A differential susceptibility to hyperoxidation was observed for the two Arabidopsis 2-CysPRX isoforms and among the proteins of the three species, and was associated to sequence variation in hyperoxidation resistance motifs. Alkylation experiments indicate that only a minor fraction of the 2-CysPRX pool carries one free thiol in the three species, and that this content does not change during the light period. We conclude that most plastidial 2-CysPRX forms are oxidized and propose that there is a species-dependent variability in their functions since dimer and hyperoxidized forms fulfill distinct roles regarding direct oxidation of partners and signal transmission.

Divergent Approaches to Virulence in C. albicans and C. glabrata: Two Sides of the Same Coin.

Candida albicans and Candida glabrata are the two most prevalent etiologic agents of candidiasis worldwide. Although both are recognized as pathogenic, their choice of virulence traits is highly divergent. Indeed, it appears that these different approaches to fungal virulence may be equally successful in causing human candidiasis. In this review, the virulence mechanisms employed by C. albicans and C. glabrata are analyzed, with emphasis on the differences between the two systems. Pathogenesis features considered in this paper include dimorphic growth, secreted enzymes and signaling molecules, and stress resistance mechanisms. The consequences of these traits in tissue invasion, biofilm formation, immune system evasion, and macrophage escape, in a species dependent manner, are discussed. This review highlights the observation that C. albicans and C. glabrata follow different paths leading to a similar outcome. It also highlights the lack of knowledge on some of the specific mechanisms underlying C. glabrata pathogenesis, which deserve future scrutiny.