Chemotactic responses of Trypanosoma brucei procyclic forms to proline and other metabolites

Glycerol metabolism triggers trypanosome differentiation into transmissible forms in mammalian tissue-like conditions

In the mammalian bloodstream, Trypanosoma brucei, the parasite responsible for sleeping sickness, proliferates as slender forms before undergoing quorum-sensing (QS)-mediated differentiation into cell cycle-arrested stumpy forms (stumpy-QS), a transition that regulates parasitaemia and primes parasites for tsetse fly transmission. Beyond the bloodstream, T. brucei also occupies extravascular, adipose-rich tissues such as the skin, a potential reservoir for transmission. Here, we identify an alternative slender-to-stumpy differentiation pathway driven by glycerol, a host metabolite abundant in adipose-rich tissues, that could resolve the long-standing paradox of successful parasite transmission from human hosts during chronic infection despite low parasitaemia. We show that high (10 mM) and non-physiological glycerol concentrations under low glucose conditions (0.5 mM) induce differentiation, generating distinct stumpy-Glyc forms that resemble stumpy-QS parasites but have an extended lifespan. Under conditions mimicking dermal tissue interstitial fluids (4 mM glucose, 0.25 mM glycerol), we show that glycerol promotes the emergence of proliferative intermediate forms that retain transmission potential and can differentiate into fly host-specific procyclic forms in vitro and within tsetse flies. These findings open the door for reevaluation of the model of T. brucei transmission and supports a dominant role for adipocyte-derived glycerol in the skin in sustaining parasite transmission.

Targeting methyl-accepting chemotaxis transmembrane sensory protein inhibits Helicobacter pylori autoinducer-2 quorum sensing system

Findings suggest that Withaferin A and Obacunone could serve as promising therapeutic agents against H. pylori infections by disrupting quorum sensing and biofilm formation, thus addressing the challenge of antibiotic resistance in this pathogen.

Saccharomycopsis schoenii: A Model Predatory Yeast Provides Insights into Evolution, Genomics and Biocontrol

Fungal mycoparasitism, where one fungus preys on another, offers a sustainable, eco-friendly alternative to synthetic chemical fungicides in agriculture and conventional antifungal therapies to manage clinical pathogens. The budding yeast Saccharomycopsis schoenii has emerged as a compelling model for contact-dependent, necrotrophic predation. Belonging to the CUG-Ser2 clade, its obligate predatory lifestyle is characterized by extensive genomic restructuring, including the loss of the sulfate assimilation pathway, which couples methionine starvation to a predatory behavioral switch. In this review, we highlight recent comparative genomics and functional studies as they relate to S. schoenii predation. For example, S. schoenii uses rewired mitogen-activated protein kinase (MAPK) signaling, actin-based penetration pegs and a large tandem expansion of secreted aspartic proteases (SAPs) to breach prey cell walls. Analysis of its genome reveals structural adaptations, including AT-rich regional centromeres and dispersed mating-type (MAT) loci. The more we learn about S. schoenii’s contact-dependent attack, the greater the opportunities to deploy S. schoenii as a safe, mycotoxin-free biocontrol agent against both multi-drug-resistant Candida auris and post-harvest Penicillium molds.

Enzymatic versatility of the salmonella effector SopB enables manipulation of host phosphoinositide signalling

Salmonella enterica relies on type III secreted effector proteins to invade host cells and establish an intracellular replicative niche, the Salmonella-containing vacuole (SCV). Among these effectors, SopB (also known as SigD) is notable for its functional versatility, contributing to virtually every stage of infection. Long characterized as a phosphoinositide phosphatase and inositol polyphosphate phosphatase, SopB was recently shown to also possess phosphotransferase activity, generating PtdIns(3,4)P2 (and, transiently, PtdIns(3,4,5)P3) de novo from PtdIns(4,5)P2 independently of PI 3-kinases and ATP. This discovery reframes how SopB activates the pro-survival kinase Akt and manipulates host signalling during invasion. Beyond its enzymatic activities, SopB engages the host Rho GTPases Cdc42 through a structurally distinct N-terminal domain and reorganizes the vimentin intermediate filament network to stabilize the SCV. In this review, we consider SopB as a paradigm for multifunctional effector biology, integrating its dual enzymatic activities, vimentin manipulation, anti-apoptotic signalling, and post-translational regulation into a unified model of how a single bacterial protein rewires host phosphoinositide metabolism across space and time.

Toxoplasma gondii Fatty Acid Elongases are Important for Virulence and Persistence

An N-acetylated daropeptide modulates nematode development.

The symbiotic bacterium Photorhabdus is a rich source of bioactive secondary metabolites that mediate tripartite interactions with nematodes and insect hosts. However, natural products of ribosomal origin remain largely underexplored within this ecological niche. Here, we report the identification of aphotorhaptin A, a darobactin-like peptide (daropeptide) natural product from Photorhabdus asymbiotica, which structurally features an ether crosslink and an N-terminal acetyl unit. Biosynthetic investigation uncovers aphotorhaptin A is matured via an unexpected leader cleavage step, and the subsequent N-terminal acetylation confers metabolic stability that maintains the hexapeptide scaffold integrity. Biochemical and structural studies demonstrate the acetyltransferase PasC exhibits remarkable substrate promiscuity, facilitated by an expansive active-site cavity that accommodates diverse acyl-CoA donors and peptide substrates. Unlike the antimicrobial darobactin, aphotorhaptin A appears to lack antibacterial activity but modulates nematode development, and this activity requires the ether crosslink and the N-terminal acetyl group in the hexapeptide scaffold. These findings expand the chemical and biosynthetic space of ribosomal peptide family and establish its link with nematode development and reproduction.