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In 2016, a 68-year-old patient with a disseminated multidrug-resistant Acinetobacter baumannii infection was successfully treated using lytic bacteriophages. Here we report the genomes of the nine phages used for treatment and three strains of A. baumannii isolated prior to and during treatment. The phages used in the initial treatment are related, T4-like myophages. Analysis of 19 A. baumannii isolates collected before and during phage treatment shows that resistance to the T4-like phages appeared two days following the start of treatment. We generate complete genomic sequences for three A. baumannii strains (TP1, TP2 and TP3) collected before and during treatment, supporting a clonal relationship. Furthermore, we use strain TP1 to select for increased resistance to five of the phages in vitro, and identify mutations that are also found in phage-insensitive isolates TP2 and TP3 (which evolved in vivo during phage treatment). These results support that in vitro investigations can produce results that are relevant to the in vivo environment. A patient with a multidrug-resistant bacterial infection was successfully treated in 2016 using phage therapy. Here, the authors sequence the genomes of the therapeutic phages and three bacterial strains isolated before and during treatment, and show that the same mutations conferring phage resistance are found in in vitro-generated mutants and in phage-insensitive strains isolated from the patient.

Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality 1 – 3 . Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The gut microbiota promotes ethanol-induced liver disease in mice 4 , but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin—a two-subunit exotoxin that is secreted by Enterococcus faecalis 5 , 6 —as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis . The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis . We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis , which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis. In patients with alcoholic hepatitis, cytolysin-positive Enterococcus faecalis strains are correlated with liver disease severity and increased mortality, and in mouse models these strains can be specifically targeted by bacteriophages.

In 2016, a 68-year-old patient with a disseminated multi-drug resistant Acinetobacter baumannii infection was treated using lytic bacteriophages in one of the first modern human clinical uses of phage therapy in the United States. Due to the emergency nature of the treatment there was little time to thoroughly characterize the phages used in this intervention or the pathogen itself. Here we report the genomes of the nine phages used for treatment and three strains of A. baumannii isolated prior to and during treatment. The eight phages used in the initial treatment were found to be a group of closely related T4-like myophages; the ninth phage, AbTP3Φ1, was found to be an unrelated Fri1-like podophage. Analysis of 19 A. baumannii isolates collected before and during phage treatment showed that resistance to the T4-like phages appeared as early as two days following the start of treatment. Three A. baumannii strains (TP1, TP2 and TP3) collected before and during treatment were sequenced to closure, and all contained a 3.9 Mb chromosome of sequence type 570 with a KL116 capsule locus and identical 8.7 kb plasmids. Phage-insensitive mutants of A. baumannii strain TP1 were generated in vitro and the majority of identified mutations were located in the bacterial capsule locus. The presence of the same mutation in both the in vitro mutants and in phage-insensitive isolates TP2 and TP3, which evolved in vivo during phage treatment, indicate that in vitro investigations can produce results that are relevant and predictive for the in vivo environment.

Leishmaniasis and Chagas disease, caused by Leishmania spp. and Trypanosoma cruzi, are neglected tropical diseases with significant global health burden, particularly in resource-limited regions. Despite their impact, diagnosis and treatment remain challenging due to limited diagnostic tools and the toxicity of available therapies. Our objective is to propose the incorporation of markers for the diagnosis of leishmaniasis and Chagas disease using ncRNA. This narrative review evaluates studies published between 2010 and 2024 (PubMed, Scopus, Google Scholar) using the SANRA scale to assess the potential of non-coding RNAs (ncRNAs) as biomarkers for these infections. Both parasites release small RNAs via extracellular vesicles that modulate host–pathogen interactions and gene expression. Although RNA interference machinery is absent in T. cruzi and most Leishmania species, it persists in early-diverging lineages. In leishmaniasis, distinct miRNA expression profiles—including miR-155-5p, miR-5011-5p, miR-6785-5p, and miR-361-3p—demonstrate high diagnostic accuracy for detecting infection (AUC up to 1.0). Serum long ncRNAs such as MALAT1 and NUTM2A-AS1 show potential diagnostic value, though clinical validation remains pending. For Chagas disease, the available evidence on ncRNAs primarily addresses the diagnosis of clinical manifestations rather than initial infection. Host miRNAs, including miR-21, miR-145, miR-146a/b, and miR-19a-3p, correlate with cardiac involvement, immune dysregulation, and inflammation during chronic T. cruzi infection. Circulating miRNAs exhibit modest sensitivity (57–67%) and specificity (57–80%) for diagnosing chronic Chagas cardiomyopathy, indicating their utility in assessing disease progression and organ damage rather than detecting early infection. This review distinguishes between ncRNAs that diagnose infection and those that evaluate disease severity or organ involvement. Altered ncRNA expression profiles represent promising biomarkers for species differentiation, treatment monitoring, and assessing cardiac complications in Chagas disease, with broader diagnostic applications emerging for leishmaniasis.

Cell spheroids are an important three-dimensional (3D) model for in vitro testing and are gaining interest for their use in clinical applications. More natural 3D cell culture environments that support cell–cell interactions have been created for cancer drug discovery and therapy applications, such as the scaffold-free 3D Petri Dish® technology. This technology uses reusable and autoclavable silicone micro-molds with different topographies, and it conventionally uses gelled agarose for hydrogel formation to preserve the topography of the selected micro-mold. The present study investigated the feasibility of using a patterned Poly(vinyl alcohol) hydrogel using the circular topography 12–81 (9 × 9 wells) micro-mold to form HeLa cancer cell spheroids and compare them with the formed spheroids using agarose hydrogels. PVA hydrogels showed a slightly softer, springier, and stickier texture than agarose hydrogels. After preparation, Fourier transform infrared (FTIR) spectra showed chemical interactions through hydrogen bonding in the PVA and agarose hydrogels. Both types of hydrogels favor the formation of large HeLa spheroids with an average diameter of around 700–800 µm after 72 h. However, the PVA spheroids are more compact than those from agarose, suggesting a potential influence of micro-mold surface chemistry on cell behavior and spheroid formation. This was additionally confirmed by evaluating the spheroid size, morphology, integrity, as well as E-cadherin and Ki67 expression. The results suggest that PVA promotes stronger cell-to-cell interactions in the spheroids. Even the integrity of PVA spheroids was maintained after exposure to the drug cisplatin. In conclusion, the patterned PVA hydrogels were successfully prepared using the 3D Petri Dish® micro-molds, and they could be used as suitable platforms for studying cell–cell interactions in cancer drug therapy.

This study investigated the fabrication of a biobased material utilizing the Pleurotus ostreatus strain, with malt dust, coffee husks, and sugarcane bagasse serving as substrates. Six substrate mixtures were formulated and subjected to solid-state fermentation. The most effective formulation—comprising 50% sugarcane bagasse and 50% malt dust—achieved complete (100%) surface colonization. After 25 days of fermentation, significant increases of 54.5% in soluble lignin and 123.2% in protein concentrations were observed, accompanied by an 11.3% decrease in pH and a reduction of 0.118 g/mL in reducing sugars. These changes suggest strong metabolic interactions between the microorganism and agro-industrial residues, indicating efficient nutrient assimilation and promoting the formation of aerial mycelia in a reticulated structure, a key feature for the development of lightweight and insulating biomaterials. Although the biomaterial exhibited an average compressive stress of 255.5 ± 27.9 kPa, it has not yet reached the mechanical performance of EPS. However, these results represent a promising step forward in the development of sustainable materials.

The Ascomycete fungus Claviceps gigantea infects maize kernels and synthetizes several alkaloids, mostly dihydrolysergamides. There is limited information on the damage these toxins cause in mammals, despite reports from infested areas with 90% presence of the fungus sclerotia. With this background, it was decided to determine the biological activity of chemical compounds present in sclerotia of C. gigantea in rabbits 38 days after weaning. Sclerotia of C. gigantea were collected in fields with high incidence of the disease, ground and analysed for nutrients. Experimental diets were prepared with four treatments, where sclerotial powder was added, substituting for alfalfa flour in increasing proportions [C. gigantea/alfalfa flour (0:100, 5:95, 15:85 and 25:75)]. Total ergot alkaloid content was analysed by high-performance liquid chromatography. Male juvenile rabbits were utilised and distributed in completely randomised design with four replications. Initial weight was recorded in each animal, and experimental diet was offered. In this study, weight of animals, feed consumption and feed conversion were evaluated in individual animals. Blood samples were taken for haemograms, and finally euthanasia was practiced. The consumption of C. gigantea had a negative effect on body weight and feed consumption. The necropsies showed anomalies proportional to the consumption of feed contaminated with the fungus.