Radek Sleha

Dendritic cells (DCs) hijacked by intracellular bacteria contribute to pathogen dissemination and immunopathology. How bacteria achieve DC subversion remains largely unknown. Here, we describe the mechanism used by tularemia agent Francisella tularensis exploiting host mitochondrial anaplerosis. Shortly after internalization, Francisella associates with DC mitochondria, which leads to the rapid repurposing of their oxidative metabolism for production of mitochondrial reactive oxygen species (mtROS). Mitochondrial metabolic rewiring is orchestrated by the intramitochondrial signaling mediated by protein acetylation and involves switching to glutamate as the primary substrate for DC tricarboxylic acid cycle. Rather than killing the bacterium, glutamate-fueled mtROS production activates p38-dependent proinflammatory gene expression. Blocking of glutamate utilization prevents DC activation and bacterial dissemination and alleviates inflammation in vivo. Our findings underscore the importance of metabolic plasticity in antibacterial DC response and open up potential avenues for therapies targeting host metabolism.

Increasing resistance to antibiotics, adverse effects of standard anti-cancer or anti-inflammatory treatments, or tumour types resistant to these treatments are leading to a search for alternatives. One of these is the use of natural products, such as bee venom, which have the same or better effect than these standard products. Bee venom has been used to treat a number of diseases for thousands of years. However, a significant obstacle remains the risk of severe allergic reactions, which can be caused by some of the more than 100 substances contained in the venom. Therefore, intensive research is currently underway to investigate not only the actual use of bee venom or its components in the above areas, but also ways to prevent these adverse effects.

An increasing resistance of microbes to antibiotics, the emergence of multidrug-resistant and extremely resistant strains, and the long time needed to develop new antibiotics are driving the search for additional sources of antibacterial agents. The aim of the study was to compare the efficacy of Czech honeys with already available pharmaceutical agents containing medicinal honey, and to perform basic biochemical analysis of Czech samples, including detection of undesirable chemical substances. The results showed strong antibacterial activity of Czech honeydew honeys compared to the control group, especially against G+ pathogens, with an average MIC of 9.44% compared to 17.54%, and comparable activity against G− of 16.48% versus 16.66%. In addition to the strong antibacterial activity, this study confirmed the safety and quality of Czech honeys and helped to select the character of a possible source for in vivo testing and subsequent clinical trials.

Aside from the general population, the COVID-19 pandemic has also affected a group of patients in palliative oncology care. In this study, long-term immune responses against SARS-CoV-2 after vaccination were monitored in a cohort of patients in palliative oncology care. This non-randomized, prospective, and open-label pilot study recruited patients from the Palliative Oncology Program and included 147 patients, of which 80 were females (54.4%) and 67 males (45.6%). The overall evaluation included current health status, SARS-CoV-2 anti-S IgG titer, and neutralizing antibodies using the SARS-CoV-2 virus neutralization test (VNT). Anti-S IgG antibody analysis revealed high (H) antibody levels in 35.7% (n = 10) and very high (VH) levels in 39.3% (n = 11) of patients after the second vaccination dose. Similarly, after the third dose, H was found in 29.6% (n = 32) and VH in 55.5% (n = 60) of patients. High and very high anti-S IgG antibody levels were consistent with high VNT titers (>2560) and H antibody levels in 17.1% (n = 12) or VH in 82.9% (n = 58) of patients. Patients with two or more doses showed H and VH antibody levels at a median of 451 and 342 days after vaccination, respectively. In this clinical trial, patients showed high and very high levels of anti-S IgG antibodies over a longer period of time. These patients did not show reduced immunological responses to the COVID-19 vaccine challenge. We can assume that prevention through vaccination can reduce the risk of complications or death from COVID-19 in patients in early palliative oncology care.

Marcela Slovakova, Sylva Janovska, Radek Sleha, Vera Radochova, Alexandra Hatala, Nikola Mannova, Radovan Metelka, Ludovit Pudelka, and Pavel Bostik. J. Microbiol. Biotechnol. 2024;34:663-72. https://doi.org/10.4014/jmb.2308.08008

Therapeutic regimens for the treatment of toxoplasmosis are not standardized. Treatment strategy mainly at the end of the second and the beginning of the third trimester, especially in cases of negative prenatal diagnosis, is the least uniform. In some situations, the choice of treatment may be ambiguous, and adverse drug reactions of the therapy should be taken into consideration. Adverse drug reactions of anti-toxoplasma therapy with spiramycin (n = 77) versus pyrimethamine/sulfadiazine (n = 35) were compared in 112 pregnant women. Up to 36.6% of women reported adverse reactions to the treatment overall (n = 41). Out of those 38.9% (n = 30) were treated with spiramycin and 31.4% (n = 11) with pyrimethamine/sulfadiazine. Toxic allergic reactions were the only indication for discontinuation of treatment in 8.9% of patients (n = 10), where 9.1% (n = 7) were reported in spiramycin and 8.6% (n = 3) in pyrimethamine/sulfadiazine cohort. Neurotoxic complications (acral paraesthesia) were significantly more frequent during the therapy with spiramycine in 19.5% (n = 15) compared to no cases in pyrimethamine/sulfadiazine group (p = .003). Other adverse drug reactions, such as gastrointestinal discomfort, nephrotoxicity, vaginal discomfort were reported, but the differences between the cohorts were not significant. The superiority of one of the therapeutic regimens was not statistically demonstrated, since the differences in overall toxicity or incidence of toxic allergic reactions between the cohorts were not confirmed (p = .53 and p = 1.00, respectively). However, although the isolated neurotoxicity of spiramycin was the only significant adverse reaction demonstrated in this study, pyrimethamine/sulfadiazine therapy should be preferred, because it is known to be more effective and with limited adverse reactions.

In this study, scanning electron microscopy (SEM) was used to study the cell structure of SARS-CoV-2 infected cells. Our measurements revealed infection remodeling caused by infection, including the emergence of new specialized areas where viral morphogenesis occurs at the cell membrane. Intercellular extensions for viral cell surfing have also been observed. Our results expand our knowledge of SARS-CoV-2 interactions with cells, its spread from cell to cell, and their size distribution. Our findings suggest that SEM is a useful microscopic method for intracellular ultrastructure analysis of cells exhibiting specific surface modifications that could also be applied to studying other important biological processes.