8 research outputs found
Antiviral, antimicrobial and antibiofilm activity of selenoesters and selenoanhydrides
Selenoesters and the selenium isostere of phthalic anhydride are bioactive selenium
compounds with a reported promising activity in cancer, both due to their cytotoxicity and capacity
to reverse multidrug resistance. Herein we evaluate the antiviral, the biofilm inhibitory, the
antibacterial and the antifungal activities of these compounds. The selenoanhydride and 7 out
of the 10 selenoesters were especially potent antiviral agents in Vero cells infected with herpes
simplex virus-2 (HSV-2). In addition, the tested selenium derivatives showed interesting antibiofilm
activity against Staphylococcus aureus and Salmonella enterica serovar Typhimurium, as well as a
moderate antifungal activity in resistant strains of Candida spp. They were inactive against anaerobes,
which may indicate that the mechanism of action of these derivatives depends on the presence of
oxygen. The capacity to inhibit the bacterial biofilm can be of particular interest in the treatment
of nosocomial infections and in the coating of surfaces of prostheses. Finally, the potent antiviral
activity observed converts these selenium derivatives into promising antiviral agents with potential
medical applications.
Selenocompounds as Novel Antibacterial Agents and Bacterial Efflux Pump Inhibitors
Bacterial multidrug resistance is becoming a growing problem for public health, due to
the development and spreading of bacterial strains resistant to antimicrobials. In this study, the
antibacterial and multidrug resistance reversing activity of a series of seleno-carbonyl compounds
has been evaluated. The effects of eleven selenocompounds on bacterial growth were evaluated in
Staphylococcus aureus, methicillin resistant S. aureus (MRSA), Enterococcus faecalis, Escherichia coli, and
Chlamydia trachomatis D. The combination effect of compounds with antibiotics was examined by the
minimum inhibitory concentration reduction assay. Their efflux pump (EP) inhibitory properties
were assessed using real-time fluorimetry. Relative expressions of EP and quorum-sensing genes
were studied by quantitative PCR. Results showed that a methylketone selenoester had remarkable
antibacterial activity against Gram-positive bacteria and potentiated the activity of oxacillin in MRSA.
Most of the selenocompounds showed significant anti-chlamydial effects. The selenoanhydride
and the diselenodiester were active inhibitors of the AcrAB-TolC system. Based on these results
it can be concluded that this group of selenocompounds can be attractive potential antibacterials
and EP inhibitors. The discovery of new derivatives with a significant antibacterial activity as novel
selenocompounds, is of high impact in the fight against resistant pathogen
Antiviral, antimicrobial and antibiofilm activity of selenoesters and selenoanhydrides
Selenoesters and the selenium isostere of phthalic anhydride are bioactive selenium
compounds with a reported promising activity in cancer, both due to their cytotoxicity and capacity
to reverse multidrug resistance. Herein we evaluate the antiviral, the biofilm inhibitory, the
antibacterial and the antifungal activities of these compounds. The selenoanhydride and 7 out
of the 10 selenoesters were especially potent antiviral agents in Vero cells infected with herpes
simplex virus-2 (HSV-2). In addition, the tested selenium derivatives showed interesting antibiofilm
activity against Staphylococcus aureus and Salmonella enterica serovar Typhimurium, as well as a
moderate antifungal activity in resistant strains of Candida spp. They were inactive against anaerobes,
which may indicate that the mechanism of action of these derivatives depends on the presence of
oxygen. The capacity to inhibit the bacterial biofilm can be of particular interest in the treatment
of nosocomial infections and in the coating of surfaces of prostheses. Finally, the potent antiviral
activity observed converts these selenium derivatives into promising antiviral agents with potential
medical applications.
Selenocompounds as Novel Antibacterial Agents and Bacterial Efflux Pump Inhibitors
Bacterial multidrug resistance is becoming a growing problem for public health, due to
the development and spreading of bacterial strains resistant to antimicrobials. In this study, the
antibacterial and multidrug resistance reversing activity of a series of seleno-carbonyl compounds
has been evaluated. The effects of eleven selenocompounds on bacterial growth were evaluated in
Staphylococcus aureus, methicillin resistant S. aureus (MRSA), Enterococcus faecalis, Escherichia coli, and
Chlamydia trachomatis D. The combination effect of compounds with antibiotics was examined by the
minimum inhibitory concentration reduction assay. Their efflux pump (EP) inhibitory properties
were assessed using real-time fluorimetry. Relative expressions of EP and quorum-sensing genes
were studied by quantitative PCR. Results showed that a methylketone selenoester had remarkable
antibacterial activity against Gram-positive bacteria and potentiated the activity of oxacillin in MRSA.
Most of the selenocompounds showed significant anti-chlamydial effects. The selenoanhydride
and the diselenodiester were active inhibitors of the AcrAB-TolC system. Based on these results
it can be concluded that this group of selenocompounds can be attractive potential antibacterials
and EP inhibitors. The discovery of new derivatives with a significant antibacterial activity as novel
selenocompounds, is of high impact in the fight against resistant pathogen
Guidelines for the use and interpretation of assays for monitoring autophagy
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field
Guidelines for the use and interpretation of assays for monitoring autophagy
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field