Imide and isatin derivatives as β-lactam mimics of β-lactam antibiotics

Activated γ-lactams, which are derivatives of succinimide, phthalimide and isatin with suitable elements of molecular recognition, have been synthesised as mimics of the ß-lactam antibiotics and their chemical and biological reactivity determined

Hall effect in laser ablated Co_2(Mn,Fe)Si thin films

Pulsed laser deposition was employed to grow thin films of the Heusler compounds Co_2MnSi and Co_2FeSi. Epitaxial growth was realized both directly on MgO (100) and on a Cr or Fe buffer layer. Structural analysis by x-ray and electron diffraction shows for both materials the ordered L2_1 structure. Bulk magnetization was determined with a SQUID magnetometer. The values agree with the Slater-Pauling rule for half-metallic Heusler compounds. On the films grown directly on the substrate measurements of the Hall effect have been performed. The normal Hall effect is nearly temperature independent and points towards a compensated Fermi surface. The anomalous contribution is found to be dominated by skew scattering. A remarkable sign change of both normal and anomalous Hall coefficients is observed on changing the valence electron count from 29 (Mn) to 30 (Fe).Comment: 9 pages, 6 figures submitted to J Phys

S. epidermidis response to human blood and its cellular and soluble components

Staphylococcus epidermidis, a normal inhabitant of healthy human skin and mucosae, can cause persistent and relapsing infections due to its ability to adhere to medical devices and form biofilms. Hence, S epidermidis is considered one of the most important medical device-associated nosocomial agents, being particularly associated with vascular catheters. Although the biofilms formed on these catheters are in constant contact with human blood, their mutual interaction is poorly understood. Here, we evaluated the expression of genes associated with biofilm formation (icaA, aap, bhp), immune evasion (icaA, mprF, sepA) and programmed cell death (lrgB), as well as biofilm structure and viability, upon bacterial interaction with human blood and its components. We observed that contact with human blood increased the transcription of icaA and bhp but decreased aap, sepA and lrgB gene expression, when compared with plasma. In contrast, no significant transcriptional alterations were detected upon contact with purified mononuclear cells, whereas purified polymorphonuclear cells lead to increased bhp and mprF gene expression. Furthermore, human blood reduced by 50% the number of viable cells within the biofilm and induced significant alterations in its structure, with the creation of a fibre-like matrix. In conclusion, our study reveals that S. epidermis biofilms adapt to particular environmental stress by changing the expression of specific genes and by altering their structure. Despite these overall observations, significant variability was found between different blood donors, suggesting that particularities of the host immune system may strongly affect the outcome of S. epidermidis infections

Monoclonal antibody raised against PNAG has variable effects on static S. epidermidis biofilm accumulation in vitro

This work was funded by FEDER funds through the Operational Programme for Competitiveness Factors – COMPETE and by National Funds through FCT – Foundation for Science and Technology under the project Pest-C/ EQB/LA0006/2013. C. S. and F. G. were supported by post-doctoral grants from Fundação para a Ciência e a Tecnologia (SFRH/BPD/70548/2010 and SFRH/BPD/95556/2013, respectively)

Characterization of an in vitro fed-batch model to obtain cells released from S. epidermidis biofilms

Both dynamic and fed-batch systems have been used for the study of biofilms. Dynamic systems, whose hallmark is the presence of continuous flow, have been considered the most appropriate for the study of the last stage of the biofilm lifecycle: biofilm disassembly. However, fed-batch is still the most used system in the biofilm research field. Hence, we have used a fed-batch system to collect cells released from Staphylococcus epidermidis biofilms, one of the most important etiological agents of medical device-associated biofilm infections. Herein, we showed that using this model it was possible to collect cells released from biofilms formed by 12 different S. epidermidis clinical and commensal isolates. In addition, our data indicated that biofilm disassembly occurred by both passive and active mechanisms, although the last occurred to a lesser extent. Moreover, it was observed that S. epidermidis biofilm-released cells presented higher tolerance to vancomycin and tetracycline, as well as a particular gene expression phenotype when compared with either biofilm or planktonic cells. Using this model, biofilm-released cells phenotype and their interaction with the host immune system could be studied in more detail, which could help providing significant insights into the pathophysiology of biofilm-related infections.European Union funds (FEDER/COMPETE) and by national funds (Fundação para a Ciência e a Tecnologia-FCT) under the project with reference FCOMP-01-0124-FEDER-041246 (EXPL/BIA-MIC/0101/2013). The authors thank the FCT Strategic Project of UID/BIO/04469/2013 unit and the project FCOMP-01-0124-FEDER-027462 (RECI/BBB-EBI/0179/2012); SFRH/BPD/99961/2014 and SFRH/BD/78235/201

The pathogenesis of Staphylococcus epidermidis biofilm-associated infections: the host and the pathogen perspective

Book of Abstracts of CEB Annual Meeting 2017info:eu-repo/semantics/publishedVersio

Biofilm dormancy enhances antimicrobial tolerance in S. epidermidis

Our well-being and our microbes Annual Meeting of the New Zealand Microbiological SocietyIndwelling medical devices have been increasingly used in modern medicine and have saved millions of lives worldwide. However, they can also be an important source of infections, most commonly caused by coagulase negative-staphylococci, particularly by biofilm forming Staphylococcus epidermidis. A key feature of biofilms is its enhanced tolerance to antibiotics. Several mechanisms have been proposed to contribute to this phenomenon. We recently developed an in vitro model able to stimulate the induction or prevention of biofilm dormancy. Herein, we used that model to determine if biofilms with induced dormancy presented a distinct antimicrobial tolerance profile than biofilms with prevented dormancy. Both clinical or commensal isolates where included and a total of 43 unique isolates, from different parts of the world were tested. Biofilms were exposed to tetracycline, vancomycin and rifampicin and where analysed by flow citometry, CFU counts and CLSM. Three unique observations were obtained. First, biofilm dormancy was found as a widespread condition in both clinical and commensal isolates, suggesting this is a fundamental process not only related to the infectious process. Second, while vancomycin did not presented any significant effect on the tested biofilms, tetracycline and rifampicin significantly reduced the number of CFUs in biofilms with prevented dormancy tested (up to 4 log killing under 8 h), but were significantly less effective in biofilms with induced dormancy. The third and more curious observation was that the very high reduction in cultivable bacteria was not correlated with the reduction of total and viable cells. Overall, our data suggests in one hand that biofilms with induced dormancy are more tolerant to tetracycline and rifampicin and that those antibiotics further induce dormancy in biofilms, instead of effective eliminating the biofilm bacteria.info:eu-repo/semantics/publishedVersio

Molecular aspects in pathogen-fruit interactions: Virulence and resistance

Fruit losses during postharvest storage and handling due to pathogen infections are one of the major problems in the global food chain supply. The application of chemical fungicides to control diseases is currently limited by legislation in some countries and also raises concerns about food and environmental safety. Exploring molecular aspects of pathogen-fruit interactions therefore has biological and economic significance as a means to help develop rational alternatives for disease control. In this review we present the current knowledge of molecular aspects in pathogen-fruit interactions, addressing the following topics: the application of new “omics” technologies for studying these interactions; the molecular mechanisms of fungal pathogen attack; the regulation of virulence by exogenous factors; and, finally, fruit defense mechanisms.Work in Tian’s lab has been funded by the National Natural Science Foundation of China (31530057; 31371863). Work in the LGC lab has been funded by the Spanish Ministry of Economy and Competitiveness (AGL2011-30519-C03-01 and AGL2014-55802-R) and the Generalitat Valenciana (PrometeoII/2014/027). Work in the IRTA lab has been funded by the Spanish Ministry of Economy and Competitiveness by three national projects AGL2008-04828-C01/AGR, AGL2011-30519-C03/AGR and AGL2014-55287-C02.Peer reviewe