Repositioning of Antibiotics in the Treatment of Viral Infections.

Drug repurposing, also known as drug repositioning, is a currently tested approach by which new uses are being assigned for already tested drugs. In this case there are antibiotics that are used to combat bacterial infections. However, antibiotics are among the drugs that have been studied for possible antiviral activities. Therefore, the aim of this work is to carry out a review of the studies of antibiotics that could be repositioned for the treatment of viral infections. Among the main antibiotics that have demonstrated antiviral activity are macrolides and glycopeptides. In addition, several antibiotics from the group of tetracyclines, fluoroquinolones, cephalosporins and aminoglycosides have also been studied for their antiviral activity. These antibiotics have demonstrated antiviral activity against both RNA and DNA viruses, including the recent pandemic virus SARS-CoV-2. Some of these antibiotics were selected in addition to its antiviral activity for their immunomodulatory and anti-inflammatory properties. Of the antibiotics that present antiviral activity, in many cases the mechanisms of action are not exactly known. The use of these antibiotics to combat viral infections remains controversial and is not generally accepted, since clinical trials are required to prove its effectiveness. Therefore, there is currently no antibiotic approved as antiviral therapy. Hence is necessary to present the studies carried out on antibiotics that can be repositioned in the future as antiviral drugs.

Use of silver nanoparticles to control Vibrio fluvialis in cultured angelfish Pterophyllum scalare.

Nanoparticles have multiple applications, among which is their use as antimicrobial agents in aquaculture. The objective of this work was to determine the antibacterial effect of silver nanoparticles (AgNPs) against Vibrio fluvialis in cultured angelfish Pterophyllum scalare. AgNPs were synthetized through chemical reduction and characterized by UV-visible and infrared spectroscopy. Particle size ranged from 60 to 170.8 nm, and scanning electron microscopy revealed cubic and spherical forms. A minimal inhibitory concentration of 222.5 ppm was determined, as well as inhibition halos between 8.66 and 14.3 mm. Inhibition of V. fluvialis growth was observed upon contact with AgNPs. An 88% survival of infected fish was obtained when treated with AgNPs, in contrast to 100% mortality of fish that were not treated. No damage to internal or external organs was observed in fish exposed to AgNPs. We conclude that AgNPs exert an antimicrobial effect against V. fluvialis, and thus represent a new alternative to control diseases caused by this microorganism in P. scalare culture.

Community-acquired methicillin-resistant Staphylococcus aureus can persist in the throat.

Colonization by Staphylococcus aureus is an important factor in infections caused by this microorganism. Among the colonization niches of staphylococci are the nose, skin, intestinal tract, and, recently, the throat has been given relevance. Infections caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) can be fatal. Persistence of S. aureus is an important process in the pathogenesis of this microorganism and must be studied. The aim of this study was to determine the persistence of S. aureus in the throat, and characterized the strains. We studied the persistence of S. aureus for 6 years in the throat of apparently healthy people. The isolated strains from the persistent carriers were characterized through PFGE, spa-typing, SCCmec typing, resistance to methicillin, presence of virulence genes (adhesins and toxins), and the formation of biofilm. We found persistent and intermittent carriers of S. aureus in the throat, with methicillin-sensitive (MSSA), methicillin-resistant (MRSA) strains, and confirmed for the first time that CA-MRSA colonizes this niche. These strains can colonize persistently the throat for four years or more. Typification of strains through PFGE and spa-typing revealed that some carriers present the same strain, whereas others present different strains along the period of persistence. Almost all strains induced a strong biofilm formation. All strains presented adhesin and toxin genes, but no shared genotype was found. We conclude that S. aureus, including CA-MRSA strains, can remain persistently in the throat, finding a wide variability among the persistent strains.

Interaction of beauvericin in combination with antibiotics against methicillin-resistant Staphylococcus aureus and Salmonella typhimurium.

Multidrug resistance in bacteria is a major challenge worldwide, increasing both mortality by infections and costs for the health systems. Therefore, it is of utmost importance to find new drugs against resistant bacteria. Beauvericin (BEA) is a mycotoxin produced by entomopathogenic and other fungi of the genus Fusarium. Our work determines the effect of BEA combined with antibiotics, which has not been previously explored. The combination analysis included different antibiotics against non-methicillin-resistant Staphylococcus aureus (NT-MRSA), methicillin-resistant Staphylococcus aureus (MRSA), and Salmonella typhimurium. BEA showed a synergy effect with oxacillin with a fractional inhibitory concentration index (FICI) = 0.373 and an additive effect in combination with lincomycin (FICI = 0.507) against MRSA. In contrast, it was an antagonist when combined with ciprofloxacin against S. typhimurium. We propose BEA as a molecule with the potential for the development of new therapies in combination with current antibiotics against multidrug-resistant bacteria.

Molecular Characterization of Staphylococcus aureus Strains Isolated from Mobile Phones.

The widespread use of mobile phones (MP) among healthcare personnel might be considered as an important source of contamination. One of the most pathogenic bacteria to humans is Staphylococcus aureus, which can be transmitted through the constant use of MP. Nevertheless, which specific type of strains are transmitted and which are their sources have not been sufficiently studied. The aim of this study is to determine the source of contamination of MP and characterize the corresponding genotypic and phenotypic properties of the strains found. Nose, pharynx, and MP samples were taken from a group of health science students. We were able to determinate the clonality of the isolated strains by pulsed-field gel electrophoresis (PFGE) and spa gene typing (spa-type). Adhesin and toxin genes were detected, and the capacity of biofilm formation was determined. Several of the MP exhibited strains of S. aureus present in the nose and/or pharynx of their owners. methicillin-susceptible Staphylococcus aureus (MSSA), hospital-acquired methicillin-resistant S. aureus (HA-MRSA), and community-acquired methicillin-resistant S. aureus (CA-MRSA) strains were found, which indicated a variety of genotypes. This study concludes that MP can be contaminated with the strains of S. aureus present in the nose and/or pharynx of the owners; these strains can be of different types and there is no dominant genotype.

Spectroscopic Analysis and Microbicidal Effect of Ag/TiO2-SiO2 Bionanocatalysts.

Silver, especially nanostructured silver, has been found to exhibit antimicrobial properties by disrupting the function of bacterial cell walls. Nonetheless, strains of bacteria have been reported to resist silver nanoparticles. The highly efficient mutational mechanisms of bacteria, capable of overcoming modern antimicrobial compounds, make it critical to develop new materials that target genetic material, regardless of nucleotide sequence or protein structure, without being toxic to the patient. This work evaluates the microbicidal properties of a catalytic, nanostructured, organically functionalized, titanosilicate matrix (bionanocatalysts) impregnated with silver. The bionanocatalysts were synthesized by the sol-gel method using silver acetate as the silver precursor. The effect of the bionanocatalysts against clinically important strains of bacteria and yeasts was evaluated. In addition, the physicochemical composition and in vitro reactivity on DNA were studied. The antibiogram analysis revealed that the compound could inhibit the growth (inhibition halos of up to 15 ± 0.9 mm) of all the strains studied (bacteria and yeasts) at low concentrations of silver, thus reducing the toxicity associated with platinum. In this work, by adding silver in the catalytic TiO2-SiO2 matrix, the intrinsic microbicidal properties of the metal were enhanced: the results provided a valuable compound exhibiting reduced toxicity and antimicrobial effects that could potentially be used as a potent disinfectant against drug-resistant strains, as found in hospitals, for instance.

Recent Biomarkers for Monitoring the Systemic Fluoride Levels in Exposed Populations: A Systematic Review.

Fluorides are compounds that can be found in the minerals of soil with volcanic rocks. Different populations are exposed to high levels of fluorides through drinking water that, due to their chronic intake, cause several types of damage to health. Nails and hair, denominated as recent biomarkers, have been employed for monitoring systemic fluoride from long-term exposure to fluorides. The aim of this study was to perform a systematic review of the use of recent biomarkers for monitoring systemic fluoride levels in exposed populations and verify their validity in the measurement of the fluorine (F-) concentration within the body. A digital search was performed in the databases PubMed/Medline, Springer Link, Cochrane, and Scopus of original articles that employed recent biomarkers for monitoring systemic F-. Seventeen articles were included in this analysis; the recorded variables were the F- amount in each assessed biomarker, source of exposure, and total daily fluoride intake (TDFI). TDFI was associated with F- in nails and hair, as well as the exposure through drinking water. In conclusion, recent biomarkers are adequate for monitoring the systemic fluoride levels by evaluating the chronic/subchronic exposure through different sources, mainly drinking water, considering nails better than hair for this purpose.

Frequency and expression of genes involved in adhesion and biofilm formation in Staphylococcus aureus strains isolated from periodontal lesions.

BACKGROUND/PURPOSE: The aim of this study was to characterize the Staphylococcus aureus strains isolated from periodontal lesions of patients, to determine the expression of genes involved in cell adhesion upon their infection of human epithelial cells using an in vitro model, its biofilm formation, and its resistance to antibiotics. METHODS: S. aureus was analysed by PCR, Kirby-Bauer, and pulsed-field gel electrophoresis (PFGE), measuring gene expression by real-time PCR after infection of human cells in vitro. RESULTS: S. aureus was identified in 18.6% (50/268) of the samples. All strains (n = 50) possessed the virulence genes spa (Staphylococcal protein A), coa (coagulase), and icaAB (intercellular adhesin); 96% (n = 48) possessed clfB (clumping factor B), and 88% (n = 44) possessed ebps (elastin-binding protein) and sdrD (serine aspartate repeat protein D). All strains were resistant to methicillin, ampicillin, dicloxacillin, cefotaxime, and penicillin, and were multidrug resistant to 6-12 antibiotics. PFGE analysis showed 37 different pulsed-field types and most strains (60.4%) had a unique pulsed-field type. Twenty-four distinct combinations of virulence genes and antibiotic-resistant phenotypes were identified. CONCLUSION: Although S. aureus has been considered a transient member of the oral microbiota, our results indicate a high-level expression of virulence genes and multidrug resistance in the strains isolated from periodontal lesions. These strains might complicate the successful treatment of the disease.

Characterization and persistence of Staphylococcus aureus strains isolated from the anterior nares and throats of healthy carriers in a Mexican community.

Healthy carriers of Staphylococcus aureus strains have an important role in the dissemination of this bacterium. To investigate the presence of S. aureus in the throat and anterior nares, samples from 1,243 healthy volunteers in a Mexican community were examined. The percentage of healthy carriers was 59.8%. Results showed that colonization of the throat occurred more frequently than that of the nares (46.5% versus 37.1%, P<0.0001). Of the S. aureus carriers, 22.2% were exclusive nasal carriers and 38% were exclusive throat carriers. A total of 1,039 strains were isolated; 12.6% were shown to be methicillin-resistant S. aureus (MRSA). Of MRSA strains, 32.1% were isolated from exclusive throat carriers. Most of the strains isolated from the anterior nares and throat of the same carriers were the same or related; however, some were different. Pulsed-field gel electrophoresis (PFGE) pattern analysis of the MRSA strains isolated from the exclusive nasal carriers or exclusive throat carriers showed that they belong to different clusters. A 6-year prospective study was performed to investigate the persistence of S. aureus in the throat. Results showed that 13% of subjects were persistent carriers. Most of them were colonized with the same clone of S. aureus throughout the time of the study, and just three had different clones. Antimicrobial susceptibility testing showed that 91.1% of the strains were penicillin resistant. The presence of mecA and nucA genes (in order to confirm methicillin resistance) and of thermostable nuclease of S. aureus was examined. This study showed that some strains of S. aureus regularly colonized the throats of healthy people and could persist for years.

IC50 Evaluation of Platinum Nanocatalysts for Cancer Treatment in Fibroblast, HeLa, and DU-145 Cell Lines.

Cancer is a major public health problem being one of the main causes of morbidity and mortality today. Recent advances in catalytic nanomedicine have offered new cancer therapies based on the administration of nanoparticles (NPs) of platinum (Pt) dispersed in catalytic mesoporous nanomaterials (titania, TiO2) with highly selective cytotoxic properties and no adverse effects. A half maximal inhibitory concentration (IC50) study was carried out in cancerous cell lines (HeLa, DU-145, and fibroblasts) to evaluate the cytotoxic effect of different nanomaterials [Pt/TiO2, TiO2, and Pt(acac)2] synthesized by the sol-gel method at concentrations 0-1000 µg/mL. The assays showed that IC50 values for Pt in functionalized TiO2 (NPt) in HeLa (53.74 ± 2.95 µg/mL) and DU-145 (75.07 ± 5.48 µg/mL) were lower than those of pure TiO2 (74.29 ± 8.95 and 82.02 ± 6.03 µg/mL, respectively). Pt(acac)2 exhibited no cytotoxicity. Normal cells (fibroblasts) treated with NPt exhibited no significant growth inhibition, suggesting the high selectivity of the compound for cancerous cells only. TiO2 and NPt were identified as antineoplastic compounds in vitro. Pt(acac)2 is not recommendable because of the low cytotoxicity observed.

Cytotoxic Activity of Cu/TiO2 Nanoparticles on Uterine-Cervical Cancer Cells.

Nanoparticles based on metal oxides serve as carrier matrices for molecules of biological interest. In this work, we used different copper complexes that were coupled to TiO2 nanoparticles. Nanoparticles were prepared with the sol-gel method. The Cu/TiO2 nanoparticles were characterized through ultraviolet-visible and Fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, nitrogen physisorption analysis, and scanning electron microscopy. Their biological activity was determined through DNA degradation and their cytotoxic effect on HeLa cells. The Cu/TiO2 nanoparticles presented a pore size between 2 and 6 nm, the size of nanoparticles agglomerates was between 100 and 500 nm. The nanoparticles of Cu/TiO2 degraded DNA starting at 15 min. The half maximal inhibitory concentration in HeLa cells depends on the used cooper complexes, the kinetics of cell death is of first order. Results revealed that these nanoparticles could be applied in uterine-cervical cancer treatment.

Virulence gene transcription, phylogroups, and antibiotic resistance of cervico-vaginal pathogenic E. coli in Mexico.

The pathogenicity of Escherichia coli strains that cause cervico-vaginal infections (CVI) is due to the presence of several virulence genes. The objective of this study was to define the variability regarding the genotype of antibiotic resistance, the transcription profiles of virulence genes after in vitro infection of the vaginal cell line A431 and the phylogroup composition of a group of cervico-vaginal E. coli strains (CVEC). A total of 200 E. coli strains isolated from Mexican women with CVI from two medical units of the Mexican Institute of Social Security were analysed. E. coli strains and antibiotic resistance genes were identified using conventional polymerase chain reaction (PCR), and phylogroups were identified using multiplex PCR. Virulence gene transcription was measured through reverse-transcriptase real-time PCR after infection of the vaginal cell line A431. The most common antibiotic resistance genes among the CVEC strains were aac(3)II, TEM, dfrA1, sul1, and qnrA. The predominant phylogroup was B2. The genes most frequently transcribed in these strains were fimH, papC, irp2, iroN, kpsMTII, cnf1, and ompT, mainly in CVEC strains isolated from chronic and occasional vaginal infections. The strains showed a large diversity of transcription of the virulence genes phenotype and antibiotic resistance genotype, especially in the strains of phylogroups, B2, A, and D. The strains formed 2 large clusters, which contained several subclusters. The genetic diversity of CVEC strains was high. These strains have a large number of transcription patterns of virulence genes, and one-third of them carry three to seven antibiotic resistance genes.

Variations in oxygen concentration cause differential antioxidant response and expression of related genes in Beauveria bassiana.

The entomopathogenic fungus Beauveria bassiana is widely used in pest biocontrol strategies. We evaluated both the antioxidant response mediated by compatible solutes, trehalose or mannitol, and the expression of related genes using oxygen pulses at three oxygen concentrations in solid state culture (SSC): normal atmosphere (21% O2), low oxygen (16% O2) and enriched oxygen (26% O2). Trehalose concentration decreased 75% after atmospheric modifications in the cultures, whereas mannitol synthesis was three-fold higher under the 16% O2 pulses relative to normal atmosphere (100 and 30 µg mannitol mg(-1) biomass, respectively). Confirming this result, expression of the mpd gene, coding for mannitol-1-P dehydrogenase (MPD), increased up to 1.4 times after O2 pulses. The expression of the bbrgs1 gene, encoding a regulatory G protein related to conidiation, was analysed to explain previously reported differences in conidial production. Surprisingly, expression of bbrgs1 decreased after atmospheric modification. Finally, principal component analysis (PCA) indicated that 83.39% of the variability in the data could be explained by two components. This analysis corroborated the positive correlation between mannitol concentration and mpd gene expression, as well as the negative correlation between conidial production and bbrgs1 gene expression. This study contributes to understanding of antioxidant and molecular response of B. bassiana induced under oxidant conditions.

Isolation of community-acquired methicillin-resistant Staphylococcus aureus in healthy carriers in a Mexican community.

OBJECTIVES: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) clones are spreading rapidly among the population in many regions worldwide. Little information is available on CA-MRSA in Mexico. The aim of this study was to identify CA-MRSA strains in the nose and throat of healthy people in a Mexican community. METHODS: A total of 131 MRSA strains from the nose and throat obtained from healthy people in Mexico City were characterized. The genes mecA, lukS-PV/lukF-PV, and ACME-arcA were detected by PCR. Staphylococcal cassette chromosome mec (SCCmec), pulsed-field gel electrophoresis (PFGE), and spa typing were performed. RESULTS: Bacteria that had a Panton-Valentine leukocidin (PVL)-positive gene and SCCmec type IV or V were designated as CA-MRSA strains. We found that 21.4% of MRSA strains were CA-MRSA and that the percentage of CA-MRSA strains was similar in the nose and the throat. A great diversity of profiles was found in the strains identified by PFGE pattern and spa typing. Only one strain similar to the USA300 genotype was found; this strain carried the ACME-arcA gene. CONCLUSIONS: CA-MRSA strains were detected in the nose and throat of healthy people. We identified a high level of genetic diversity among CA-MRSA strains in healthy people of Mexico City, which were different from the USA and pandemic clone profiles.