Bio-based matrix photocatalysts for photodegradation of antibiotics.

Antibiotics development during the last century permitted unprecedent medical advances. However, it is undeniable that there has been an abuse and misuse of antimicrobials in medicine and cosmetics, food production and food processing, in the last decades. The pay toll for human development and consumism is the emergence of extended antimicrobial resistance and omnipresent contamination of the biosphere. The One Health concept recognizes the interconnection of human, environmental and animal health, being impossible alter one without affecting the others. In this context, antibiotic decontamination from water-sources is of upmost importance, with new and more efficient strategies needed. In this framework, light-driven antibiotic degradation has gained interest in the last few years, strongly relying in semiconductor photocatalysts. To improve the semiconductor properties (i.e., efficiency, recovery, bandgap width, dispersibility, wavelength excitation, etc.), bio-based supporting material as photocatalysts matrices have been thoroughly studied, exploring synergetic effects as operating parameters that could improve the photodegradation of antibiotics. The present work describes some of the most relevant advances of the last 5 years on photodegradation of antibiotics and other antimicrobial molecules. It presents the conjugation of semiconductor photocatalysts to different organic scaffolds (biochar and biopolymers), then to describe hybrid systems based on g-C3N4 and finally addressing the emerging use of organic photocatalysts. These systems were developed for the degradation of several antibiotics and antimicrobials, and tested under different conditions, which are analyzed and thoroughly discussed along the work.

Latest trends on photodynamic disinfection of Gram-negative bacteria: photosensitizer's structure and delivery systems.

Antimicrobial resistance is threatening to overshadow last century's medical advances. Etiological agents of previously eradicated infectious diseases are now resurgent as multidrug-resistant strains, especially for Gram-negative strains. Finding new therapeutic solutions is a real challenge for our society. In this framework, Photodynamic Antimicrobial ChemoTherapy relies on the generation of toxic reactive oxygen species in the presence of light, oxygen, and a photosensitizer molecule. The use of reactive oxygen species is common for disinfection processes, using chemical agents, such as chlorine and hydrogen peroxide, and as they do not have a specific molecular target, it decreases the potential of tolerance to the antimicrobial treatment. However, light-driven generated reactive species result in an interesting alternative, as reactive species generation can be easily tuned with light irradiation and several PSs are known for their low environmental impact. Over the past few years, this topic has been thoroughly studied, exploring strategies based on single-molecule PSs (tetrapyrrolic compounds, dipyrrinate derivatives, metal complexes, etc.) or on conjunction with delivery systems. The present work describes some of the most relevant advances of the last 6 years, focusing on photosensitizers design, formulation, and potentiation, aiming for the disinfection of Gram-negative bacteria.

Photophysical and Antibacterial Properties of Porphyrins Encapsulated inside Acetylated Lignin Nanoparticles.

Lignin has recently attracted the attention of the scientific community, as a suitable raw material for biomedical applications. In this work, acetylated lignin was used to encapsulate five different porphyrins, aiming to preserve their photophysical properties, and for further use as antibacterial treatment. The obtained nanoparticles were physically characterized, through dynamic light scattering size measurement, polydispersity index and zeta potential values. Additionally, the photophysical properties of the nanoparticles, namely UV-vis absorption, fluorescence emission, singlet oxygen production and photobleaching, were compared with those of the free porphyrins. It was found that all the porphyrins were susceptible to encapsulation, with an observed decrease in their fluorescence quantum yield and singlet oxygen production. These nanoparticles were able to exert an effective photodynamic bactericide effect (blue-LED light, 450-460 nm, 15 J/cm2) on Staphylococcus aureus and Escherichia coli. Furthermore, it was achieved a photodynamic bactericidal activity on an encapsulated lipophillic porphyrin, where the free porphyrin failed to diminish the bacterial survival. In this work it was demonstrated that acetylated lignin encapsulation works as a universal, cheap and green material for the delivery of porphyrins, while preserving their photophysical properties.

Porphyrin-Loaded Lignin Nanoparticles Against Bacteria: A Photodynamic Antimicrobial Chemotherapy Application.

The need for alternative strategies to fight bacteria is evident from the emergence of antimicrobial resistance. To that respect, photodynamic antimicrobial chemotherapy steadily rises in bacterial eradication by using light, a photosensitizer and oxygen, which generates reactive oxygen species that may kill bacteria. Herein, we report the encapsulation of 5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphyrin into acetylated lignin water-dispersible nanoparticles (THPP@AcLi), with characterization of those systems by standard spectroscopic and microscopic techniques. We observed that THPP@AcLi retained porphyrin's photophysical/photochemical properties, including singlet oxygen generation and fluorescence. Besides, the nanoparticles demonstrated enhanced stability on storage and light bleaching. THPP@AcLi were evaluated as photosensitizers against two Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, and against three Gram-positive bacteria, Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis. THPP@AcLi were able to diminish Gram-positive bacterial survival to 0.1% when exposed to low white LED light doses (4.16 J/cm2), requiring concentrations below 5 µM. Nevertheless, the obtained nanoparticles were unable to diminish the survival of Gram-negative bacteria. Through transmission electron microscopy observations, we could demonstrate that nanoparticles did not penetrate inside the bacterial cell, exerting their destructive effect on the bacterial wall; also, a high affinity between acetylated lignin nanoparticles and bacteria was observed, leading to bacterial flocculation. Altogether, these findings allow to establish a photodynamic antimicrobial chemotherapy alternative that can be used effectively against Gram-positive topic infections using the widely available natural polymeric lignin as a drug carrier. Further research, aimed to inhibit the growth and survival of Gram-negative bacteria, is likely to enhance the wideness of acetylated lignin nanoparticle applications.

Correction to: Deletion of the hypothetical protein SCO2127 of Streptomyces coelicolor allowed identification of a new regulator of actinorhodin production.

The published online version of this paper contains mistake. The authors first and last names have been interchanged. The correct version is given above.

Conjugating biomaterials with photosensitizers: advances and perspectives for photodynamic antimicrobial chemotherapy.

Antimicrobial resistance is threatening to overshadow last century's medical advances. Previously eradicated infectious diseases are now resurgent as multi-drug resistant strains, leading to expensive, toxic and, in some cases, ineffective antimicrobial treatments. Given this outlook, researchers are willing to investigate novel antimicrobial treatments that may be able to deal with antimicrobial resistance, namely photodynamic therapy (PDT). PDT relies on the generation of toxic reactive oxygen species (ROS) in the presence of light and a photosensitizer (PS) molecule. PDT has been known for almost a century, but most of its applications have been directed towards the treatment of cancer and topical diseases. Unlike classical antimicrobial chemotherapy treatments, photodynamic antimicrobial chemotherapy (PACT) has a non-target specific mechanism of action, based on the generation of ROS, working against cellular membranes, walls, proteins, lipids and nucleic acids. This non-specific mechanism diminishes the chances of bacteria developing resistance. However, PSs usually are large molecules, prone to aggregation, diminishing their efficiency. This review will report the development of materials obtained from natural sources, as delivery systems for photosensitizing molecules against microorganisms. The present work emphasizes on the biological results rather than on the synthesis routes to prepare the conjugates. Also, it discusses the current state of the art, providing our perspective on the field.

Acetylated lignin nanoparticles as a possible vehicle for photosensitizing molecules.

Lignins are underused and abundant bio-sourced polymers with various potential applications. An attractive one is the development of nanoparticles for bioactive compound delivery. Here, we optimized the synthesis of hydrodispersible nanoparticles of acetylated lignin by comparing different lignin sources, degrees of acetylation and preparation methods. The formation of acetylated lignin nanoparticles in various solvents was probed by both experiments and, for the first time, a molecular dynamics simulation. We showed that dialysis is more suitable to obtain these nanoparticles than anti-solvent addition. The encapsulation of hydrophobic photosensitizing porphyrin in these nanoparticles was also demonstrated and rationalized at the molecular level, together with experiments, docking and molecular dynamics simulations. As acetylated lignin has been demonstrated to exhibit photosensitizing activity, the encapsulation of bioactive compounds in lignin nanoparticles opens the doors to a broad range of potential applications.

Impact of ∼omics in the detection and validation of potential anti-infective drugs.

New anti-infective drugs are an unmet necessity of modern medicine. The use of ∼omics technologies has exponentially increased the knowledge on active anti-infective structures, where to search for them and their mechanisms of action. Research involving extreme and unique environments (such as endophytes) revealed their potential for many yet unknown active molecules. This work intends to review a recent research involving discovery of secondary metabolites with an established anti-infective action which was mediated by one of the ∼omics sciences: genomics, proteomics, transcriptomics, metabolomics, glycomics or their combinations, as well as the software at the base of these discoveries.

Interplay between carbon, nitrogen and phosphate utilization in the control of secondary metabolite production in Streptomyces.

Streptomyces species are a wide and diverse source of many therapeutic agents (antimicrobials, antineoplastic and antioxidants, to name a few) and represent an important source of compounds with potential applications in medicine. The effect of nitrogen, phosphate and carbon on the production of secondary metabolites has long been observed, but it was not until recently that the molecular mechanisms on which these effects rely were ascertained. In addition to the specific macronutrient regulatory mechanisms, there is a complex network of interactions between these mechanisms influencing secondary metabolism. In this article, we review the recent advances in our understanding of the molecular mechanisms of regulation exerted by nitrogen, phosphate and carbon sources, as well as the effects of their interconnections, on the synthesis of secondary metabolites by members of the genus Streptomyces.

Carbon catabolite regulation in Streptomyces: new insights and lessons learned.

One of the most significant control mechanisms of the physiological processes in the genus Streptomyces is carbon catabolite repression (CCR). This mechanism controls the expression of genes involved in the uptake and utilization of alternative carbon sources in Streptomyces and is mostly independent of the phosphoenolpyruvate phosphotransferase system (PTS). CCR also affects morphological differentiation and the synthesis of secondary metabolites, although not all secondary metabolite genes are equally sensitive to the control by the carbon source. Even when the outcome effect of CCR in bacteria is the same, their essential mechanisms can be rather different. Although usually, glucose elicits this phenomenon, other rapidly metabolized carbon sources can also cause CCR. Multiple efforts have been put through to the understanding of the mechanism of CCR in this genus. However, a reasonable mechanism to explain the nature of this process in Streptomyces does not yet exist. Several examples of primary and secondary metabolites subject to CCR will be examined in this review. Additionally, recent advances in the metabolites and protein factors involved in the Streptomyces CCR, as well as their mechanisms will be described and discussed in this review.

Deletion of the hypothetical protein SCO2127 of Streptomyces coelicolor allowed identification of a new regulator of actinorhodin production.

Although the specific function of SCO2127 remains elusive, it has been assumed that this hypothetical protein plays an important role in carbon catabolite regulation and therefore in antibiotic biosynthesis in Streptomyces coelicolor. To shed light on the functional relationship of SCO2127 to the biosynthesis of actinorhodin, a detailed analysis of the proteins differentially produced between the strain M145 and the Δsco2127 mutant of S. coelicolor was performed. The delayed morphological differentiation and impaired production of actinorhodin showed by the deletion strain were accompanied by increased abundance of gluconeogenic enzymes, as well as downregulation of both glycolysis and acetyl-CoA carboxylase. Repression of mycothiol biosynthetic enzymes was further observed in the absence of SCO2127, in addition to upregulation of hydroxyectoine biosynthetic enzymes and SCO0204, which controls nitrite formation. The data generated in this study reveal that the response regulator SCO0204 greatly contributes to prevent the formation of actinorhodin in the ∆sco2127 mutant, likely through the activation of some proteins associated with oxidative stress that include the nitrite producer SCO0216.

Synthesis of new 1,2,3-triazole derivatives of uracil and thymine with potential inhibitory activity against acidic corrosion of steels.

Ten 1,4-disubstituted 1,2,3-triazoles were synthesized from one of 1-(azido-methyl)benzene, 1-(azidomethyl)-4-fluorobenzene, 1-(azidomethyl)-4-chlorobenzene, 1-(azidomethyl)-4-bromobenzene or 1-(azidomethyl)-4-iodobenzene, generated in situ from sodium azide and the corresponding benzyl halide, and dipropargyl uracil or dipropargyl thymine. Optimal experimental conditions were established for the conventional click chemistry. The corrosion inhibiting properties of some of these compounds, which were determined by means of an electrochemical technique, are also presented.