Synergistic antibacterial effects of exopolysaccharides/nickel-nanoparticles composites against multidrug-resistant bacteria.

The need for an alternative treatment to fight infectious diseases caused by antibiotic-resistant bacteria is increasing. A possible way to overcome bacterial resistance to antibiotics is by reintroducing commonly used antibiotics with a sensitizer capable of enhancing their antimicrobial effect in resistant bacteria. Here, we use a composite composed of exopolysaccharide capped-NiO NPs, with antimicrobial effects against antibiotic-resistant Gram-positive and Gram-negative bacteria. It potentiated the antimicrobial effects of four different antibiotics (ampicillin, kanamycin, chloramphenicol, and ciprofloxacin) at lower concentrations than their minimal inhibitory concentrations. We observed that the Ni-composite synergistically enhanced, fourfold, the antibacterial effect of kanamycin and chloramphenicol against multidrug-resistant Staphylococcus aureus and Pseudomonas aeruginosa, as well as ampicillin against multidrug-resistant Staphylococcus aureus, and ciprofloxacin against multidrug-resistant Pseudomonas aeruginosa by eightfold. We also found that Ni-composite could not inhibit biofilm synthesis on the tested bacterial strains. Our results demonstrated the possibility of using metal nanoparticles, like NiO, as a sensitizer to overcome bacterial antibiotic resistance.

Nanomaterial-Based Antifungal Therapies to Combat Fungal Diseases Aspergillosis, Coccidioidomycosis, Mucormycosis, and Candidiasis.

Over the last years, invasive infections caused by filamentous fungi have constituted a serious threat to public health worldwide. Aspergillus, Coccidioides, Mucorales (the most common filamentous fungi), and Candida auris (non-filamentous fungus) can cause infections in humans. They are able to cause critical life-threatening illnesses in immunosuppressed individuals, patients with HIV/AIDS, uncontrolled diabetes, hematological diseases, transplantation, and chemotherapy. In this review, we describe the available nanoformulations (both metallic and polymers-based nanoparticles) developed to increase efficacy and reduce the number of adverse effects after the administration of conventional antifungals. To treat aspergillosis and infections caused by Candida, multiple strategies have been used to develop new therapeutic alternatives, such as incorporating coating materials, complexes synthesized by green chemistry, or coupled with polymers. However, the therapeutic options for coccidioidomycosis and mucormycosis are limited; most of them are in the early stages of development. Therefore, more research needs to be performed to develop new therapeutic alternatives that contribute to the progress of this field.

Exploring Functional Differences between the Right and Left Ventricles to Better Understand Right Ventricular Dysfunction.

The right and left ventricles have traditionally been studied as individual entities. Furthermore, modifications found in diseased left ventricles are assumed to influence on right ventricle alterations, but the connection is poorly understood. In this review, we describe the differences between ventricles under physiological and pathological conditions. Understanding the mechanisms that differentiate both ventricles would facilitate a more effective use of therapeutics and broaden our knowledge of right ventricle (RV) dysfunction. RV failure is the strongest predictor of mortality in pulmonary arterial hypertension, but at present, there are no definitive therapies directly targeting RV failure. We further explore the current state of drugs and molecules that improve RV failure in experimental therapeutics and clinical trials to treat pulmonary arterial hypertension and provide evidence of their potential benefits in heart failure.

The Demand for New Antibiotics: Antimicrobial Peptides, Nanoparticles, and Combinatorial Therapies as Future Strategies in Antibacterial Agent Design.

The inappropriate use of antibiotics and an inadequate control of infections have led to the emergence of resistant strains which represent a major threat to public health and the global economy. Therefore, research and development of a new generation of antimicrobials to mitigate the spread of antibiotic resistance has become imperative. Current research and technology developments have promoted the improvement of antimicrobial agents that can selectively interact with a target site (e.g., a gene or a cellular process) or a specific pathogen. Antimicrobial peptides and metal nanoparticles exemplify a novel approach to treat infectious diseases. Nonetheless, combinatorial treatments have been recently considered as an excellent platform to design and develop the next generation of antibacterial agents. The combination of different drugs offers many advantages over their use as individual chemical moieties; these include a reduction in dosage of the individual drugs, fewer side effects compared to the monotherapy, reduced risk for the development of drug resistance, a better combined response compared to the effect of the individual drugs (synergistic effects), wide-spectrum antibacterial action, and the ability to attack simultaneously multiple target sites, in many occasions leading to an increased antibacterial effect. The selection of the appropriate combinatorial treatment is critical for the successful treatment of infections. Therefore, the design of combinatorial treatments provides a pathway to develop antimicrobial therapeutics with broad-spectrum antibacterial action, bactericidal instead of bacteriostatic mechanisms of action, and better efficacy against multidrug-resistant bacteria.

Microbial Competition of Rhodotorula mucilaginosa UANL-001L and E. coli increase biosynthesis of Non-Toxic Exopolysaccharide with Applications as a Wide-Spectrum Antimicrobial.

Bacterial species are able to colonize and establish communities in biotic and abiotic surfaces. Moreover, within the past five decades, incidence of bacterial strains resistant to currently used antibiotics has increased dramatically. This has led to diverse health issues and economical losses for different industries. Therefore, there is a latent need to develop new and more efficient antimicrobials. This work reports an increased production of an exopolysaccharide in a native yeast strain isolated from the Mexican Northeast, Rhodotorula mucilaginosa UANL-001L, when co-cultured with E. coli. The exopolysaccharide produced is chemically and physically characterized and its applications as an antimicrobial and antibiofilm are explored. The exopolysaccharide is capable of inhibiting planktonic growth and biofilm formation in Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Additionally, the exopolysaccharide studied here does not exhibit cytotoxic effects when assessed both, in vitro against an H9c2 mammalian cell line, and in vivo in a murine toxicity model. Taken together, the properties of this exopolysaccharide indicate that it has potential applications to inhibit bacterial colonization in medical and industrial settlings.

Synergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial Treatments.

Due to the emergence of multi-drug resistant strains, development of novel antibiotics has become a critical issue. One promising approach is the use of transition metals, since they exhibit rapid and significant toxicity, at low concentrations, in prokaryotic cells. Nevertheless, one main drawback of transition metals is their toxicity in eukaryotic cells. Here, we show that the barriers to use them as therapeutic agents could be mitigated by combining them with silver. We demonstrate that synergism of combinatorial treatments (Silver/transition metals, including Zn, Co, Cd, Ni, and Cu) increases up to 8-fold their antimicrobial effect, when compared to their individual effects, against E. coli and B. subtilis. We find that most combinatorial treatments exhibit synergistic antimicrobial effects at low/non-toxic concentrations to human keratinocyte cells, blast and melanoma rat cell lines. Moreover, we show that silver/(Cu, Ni, and Zn) increase prokaryotic cell permeability at sub-inhibitory concentrations, demonstrating this to be a possible mechanism of the synergistic behavior. Together, these results suggest that these combinatorial treatments will play an important role in the future development of antimicrobial agents and treatments against infections. In specific, the cytotoxicity experiments show that the combinations have great potential in the treatment of topical infections.