Cellular Microbiology最新文献

Proteases are powerful enzymes, which cleave peptide bonds, leading most of the time to irreversible fragmentation or degradation of their substrates. Therefore they control many critical cell fate decisions in eukaryotes. Bacterial pathogens exploit this power and deliver protease effectors through specialised secretion systems into host cells. Research over the past years revealed that the functions of protease effectors during infection are diverse, reflecting the lifestyles and adaptations to specific hosts; however, only a small number of peptidase families seem to have given rise to most of these protease virulence factors by the evolution of different substrate-binding specificities, intracellular activation and subcellular targeting mechanisms. Here, we review our current knowledge about the enzymology and function of protease effectors, which Gram-negative bacterial pathogens translocate via type III and IV secretion systems to irreversibly manipulate host processes. We highlight emerging concepts such as signalling by protease cleavage products and effector-triggered immunity, which host cells employ to detect and defend themselves against a protease attack.

Take Away

The endosymbiont Wolbachia feminises male isopods by making them refractory to the insulin-like masculinising hormone, which shunts the autocrine development of the androgenic glands. It was, therefore, proposed that Wolbachia silences the IR receptors, either by preventing their expression or by inactivating them. We describe here the two IR paralogs of Armadillidium vulgare. They displayed a conventional structure and belonged to a family widespread among isopods. Av-IR1 displayed an ubiquist expression, whereas the expression of Av-IR2 was restricted to the gonads. Both were constitutively expressed in males and females and throughout development. However, upon silencing, altered gland physiology and gene expression therein suggested antagonistic roles for Av-IR1 (androinhibiting) and Av-IR2 (androstimulating). They may function in tandem with regulating neurohormones, as a conditional platform that conveys insulin signalling. Wolbachia infection did not alter their expression patterns: leaving the IRs unscathed, the bacteria would suppress the secretion of the neurohormones, thus inducing body-wide IR deactivation and feminisation. Adult males injected with Wolbachia acquired an intersexed physiology. Their phenotypes and gene expressions mirrored the silencing of Av-IR1 only, suggesting that imperfect feminisation stems from a flawed invasion of the androstimulating centre, whereas in fully feminised males invasion would be complete in early juveniles.

Take Away

Although the hepatitis E virus represents an uprising threat to the global community by representing the commonest cause of an acute viral hepatitis worldwide, its life cycle is grossly understudied. Albeit HEV is a non-enveloped virus, its progeny is released as quasi-enveloped virions. Thus, the responsible accessory protein pORF3 gained rising attention in the past years. It mediates viral release via the exosomal route by targeting the viral capsid to the endosomal system, more precisely to multivesicular bodies. As this is followed by quasi-envelopment, pORF3 may in terms represent a substitute to a conventional envelope protein. This feature proofs to be rather unique with respect to other enteric viruses, although the protein's role in the viral life cycle seems to reach far beyond simply maintaining release of progeny viruses. How pORF3 affects viral morphogenesis, how it mediates efficient viral release and how it supports viral spread is summarised in this microreview. With this, we aim to shed light on functions of pORF3 to gain further insights in still enigmatic aspects of the HEV life cycle.

Take Aways

The human pathogenic fungus Candida albicans is a frequent cause of mucosal infections. Although the ability to transition from the yeast to the hypha morphology is essential for virulence, hypha formation and host cell invasion per se are not sufficient for the induction of epithelial damage. Rather, the hypha-associated peptide toxin, candidalysin, a product of the Ece1 polyprotein, is the critical damaging factor. While synthetic, exogenously added candidalysin is sufficient to damage epithelial cells, the level of damage does not reach the same level as invading C. albicans hyphae. Therefore, we hypothesized that a combination of fungal attributes is required to deliver candidalysin to the invasion pocket to enable the full damaging potential of C. albicans during infection. Utilising a panel of C. albicans mutants with known virulence defects, we demonstrate that the full damage potential of C. albicans requires the coordinated delivery of candidalysin to the invasion pocket. This process requires appropriate epithelial adhesion, hyphal extension and invasion, high levels of ECE1 transcription, proper Ece1 processing and secretion of candidalysin. To confirm candidalysin delivery, we generated camelid V_HHs (nanobodies) specific for candidalysin and demonstrate localization and accumulation of the toxin only in C. albicans-induced invasion pockets. In summary, a defined combination of virulence attributes and cellular processes is critical for delivering candidalysin to the invasion pocket to enable the full damage potential of C. albicans during mucosal infection.

Take Aways

In this study, we provide evidence that galectin-3 (Gal-3) plays an important role in Brucella abortus infection. Our results showed increased Gal-3 expression and secretion in B. abortus infected macrophages and mice. Additionally, our findings indicate that Gal-3 is dispensable for Brucella-containing vacuoles disruption, inflammasome activation and pyroptosis. On the other hand, we observed that Brucella-induced Gal-3 expression is crucial for induction of molecules associated to type I IFN signalling pathway, such as IFN-β: Interferon beta (IFN-β), C-X-C motif chemokine ligand 10 (CXCL10) and guanylate-binding proteins. Gal-3 KO macrophages showed reduced bacterial numbers compared to wild-type cells, suggesting that Gal-3 facilitates bacterial replication in vitro. Moreover, priming Gal-3 KO cells with IFN-β favoured B. abortus survival in macrophages. Additionally, we also observed that Gal-3 KO mice are more resistant to B. abortus infection and these animals showed elevated production of proinflammatory cytokines when compared to control mice. Finally, we observed an increased recruitment of macrophages, dendritic cells and neutrophils in spleens of Gal-3 KO mice compared to wild-type animals. In conclusion, this study demonstrated that Brucella-induced Gal-3 is detrimental to host and this molecule is implicated in inhibition of recruitment and activation of immune cells, which promotes B. abortus spread and aggravates the infection.

Take Aways