Transcriptome analysis of macrophages during Brucella abortus infection clarifies the survival mechanisms of the bacteria.

Brucellosis is a critical zoonotic disease impacting humans and animals globally, causing symptoms like fever and arthritis in humans and reproductive issues in animals. The disease stems from the Brucella genus, adept at evading the immune system and proliferating within host cells. This study explores how Brucella abortus manipulates host cellular mechanisms to sustain infection, focusing on the interaction with murine macrophages over 24 h. Initial host defenses involve innate immune responses, while Brucella's survival strategies include evading lysosomal degradation and modulating host cell functions through various pathways. The research identified significant transcriptional changes in macrophages post-infection, highlighting pathways such as cytokine storm, pyroptosis signaling, Toll-like receptor pathways, and LXRs/RXRs signaling. The findings shed light on Brucella's complex mechanisms to undermine host defenses and underscore the need for further investigation into therapeutic targets to combat brucellosis.

H3K56 acetylation affects Candida albicans morphology and secreted soluble factors interacting with the host.

In recent years, epigenetics has been revealed as a mechanism able to modulate the expression of virulence traits in diverse pathogens, including Candida albicans. Indeed, epigenetic regulation can sense environmental changes, leading to the rapid and reversible modulation of gene expression with consequent adaptation to novel environments. How epigenetic changes can impact expression and signalling output, including events associated with mechanisms of morphological transition and virulence, is still poorly studied. Here, using nicotinamide as a sirtuin inhibitor, we explored how the accumulation of the H3K56 acetylation, the most prominent histone acetylation in C. albicans, might affect its interaction with the host. Our experiments demonstrate that H3K56 acetylation profoundly affects the production and/or secretion of soluble factors compromising actin remodelling and cytokine production. ChIP- and RNA-seq analyses highlighted a direct impact of H3K56 acetylation on genes related to phenotypic switching, biofilm formation and cell aggregation. Direct and indirect regulation also involves genes related to cell wall protein biosynthesis, ß-glucan and mannan exposure, and hydrolytic secreted enzymes, supporting the hypothesis that the fluctuations of H3K56 acetylation in C. albicans might impair the macrophage response to the yeast and thus promote the host-immune escaping.

Comparative Evaluation of Antimicrobial, Antiamoebic, and Antiviral Efficacy of Ophthalmic Formulations.

The extensive use of ophthalmic antibiotics is contributing to the appearance of resistant bacterial strains, which require prolonged and massive treatments with consequent detrimental outcomes and adverse effects. In addition to these issues, antibiotics are not effective against parasites and viruses. In this context, antiseptics could be valuable alternatives. They have nonselective mechanisms of action preventing bacterial resistance and a broad spectrum of action and are also effective against parasites and viruses. Here, we compare the in vitro antibacterial, antiameobic, and antiviral activities of six ophthalmic formulations containing antiseptics such as povidone-iodine, chlorhexidine, and thymol against Gram-positive and Gram-negative bacteria, the amoeba Acanthamoeba castellanii, and two respiratory viruses, HAdV-2 and HCoV-OC43. The results suggest that, among all the tested formulations, Dropsept, consisting of Vitamin E TPGS-based (tocopheryl polyethylene glycol succinate) in combination with the antiseptic chlorhexidine, is the one with the highest range of activities, as it works efficiently against bacteria, amoeba, and viruses. On the other hand, the solution containing PVA (polyvinyl alcohol) and thymol showed a promising inhibitory effect on Pseudomonas aeruginosa, which causes severe keratitis. Given its high efficiency, Dropsept might represent a valuable alternative to the widely used antibiotics for the treatment of ocular infections. In addition to this commercial eye drop solution, thymol-based solutions might be enrolled for their natural antimicrobial and antiamoebic effect.

Effects of Hst3p inhibition in Candida albicans: a genome-wide H3K56 acetylation analysis.

Candida spp. represent the third most frequent worldwide cause of infection in Intensive Care Units with a mortality rate of almost 40%. The classes of antifungals currently available include azoles, polyenes, echinocandins, pyrimidine derivatives, and allylamines. However, the therapeutical options for the treatment of candidiasis are drastically reduced by the increasing antifungal resistance. The growing need for a more targeted antifungal therapy is limited by the concern of finding molecules that specifically recognize the microbial cell without damaging the host. Epigenetic writers and erasers have emerged as promising targets in different contexts, including the treatment of fungal infections. In C. albicans, Hst3p, a sirtuin that deacetylates H3K56ac, represents an attractive antifungal target as it is essential for the fungus viability and virulence. Although the relevance of such epigenetic regulator is documented for the development of new antifungal therapies, the molecular mechanism behind Hst3p-mediated epigenetic regulation remains unrevealed. Here, we provide the first genome-wide profiling of H3K56ac in C. albicans resulting in H3K56ac enriched regions associated with Candida sp. pathogenicity. Upon Hst3p inhibition, 447 regions gain H3K56ac. Importantly, these genomic areas contain genes encoding for adhesin proteins, degradative enzymes, and white-opaque switching. Moreover, our RNA-seq analysis revealed 1330 upregulated and 1081 downregulated transcripts upon Hst3p inhibition, and among them, we identified 87 genes whose transcriptional increase well correlates with the enrichment of H3K56 acetylation on their promoters, including some well-known regulators of phenotypic switching and virulence. Based on our evidence, Hst3p is an appealing target for the development of new potential antifungal drugs.