Cellular Microbiology

Focused ion beam-scanning electron microscopy image of renal proximal tubule epithelial cells infected for 24 hrs with Leptospira interrogans. Leptospires localized in the gap between two adjacent cells (red and blue). For further details, readers are referred to the article by Sebastián et al. on p. e13343 of this issue.

Gram-negative bacterial pathogens employ type III and IV secretion systems to translocate a multitude of diverse effector proteins into host cells to manipulate cellular processes to their benefit. This review summarises the enzymology and functions of effector proteases, which irreversibly cleave their targets, and discusses emerging concepts in protease detection and defence mechanisms of the hosts.

The process of fungal recognition by host immune cells can involve the participation of lipid microdomains. Fungal pathogens use pattern recognition receptors (PRRs) and host cell lipid microdomains components to adhere (A). This initial step can be followed by PRRs recruitment to host microdomains during fungus association through a multi-interactive mechanism and guide internalisation (B) and/or cell signalling (C), resulting in cytokine (D) production. This association can modulate the effectiveness of host effector processes.

Immune dysregulation in the tracheal mucosa characterized by paradoxical upregulation of IFN-γ and downregulation of IL-2, depletion of CD8⁺ T-cells and possible suppression of the Th2 response against M. gallisepticum in unvaccinated chickens and the long-term protection against it afforded by vaccination with ts-304.

In Armadillidium vulgare, we described the two IR receptors of the insulin-like androgenic gland hormone (AGH). Their silencing revealed they are involved in antagonistic regulations of androgenic gland size, activity and gene expressions. Wolbachia transinfection best phenocopied IR1 silencing in inducing gland hypertrophy and hypersecretion, and the over-expression of IR2 and AGH in addition to IR1 (blue, brown and yellow arrows, respectively). Defunctionalising the whole pathway through AGH silencing led to similar effects on gland size and IR2 expression.

CDT associates with lipid rafts on the host plasma membrane and enters the cell via dynamin-dependent endocytosis. In contrast to the current model, we report that CdtA is internalised with the other Cdt subunits and co-localises with EEA1 in the early endosomes. Each Cdt subunit is rapidly degraded in the host cell, with only a minor pool of CdtB and CdtC remaining for intoxication.

The hepatitis E virus represents a non-enveloped virus, yet release of progeny virions is achieved via the viral ORF3 protein-dependent exosomal release of quasi-enveloped viral particles. While the basic principle of this specific host interaction is known, various factors being regulated by pORF3 in a host cell remain elusive. Here, we summarise the current knowledge on morphological processes, discuss which roles pORF3 may fulfil in guaranteeing efficient viral release and evaluate how these may be compromised for clinical applications.

Salmonella Typhimurium induces accumulation of cholesterol in WT macrophages (top right) but not in the absence of the host kinase FAK (bottom left) or the bacterial effector protein SseJ (bottom right). For further details, readers are referred to the article by Greene et al. on p. e13329 of this issue.

The human pathogenic fungus Candida albicans is able to cause epithelial damage. To achieve this, sequential cellular processes are essential: appropriate epithelial adhesion, hyphal extension and invasion, high levels of ECE1 transcription, proper Ece1 processing, ending in candidalysin secretion and accumulation in the invasion pocket. If any of such processes is impaired, epithelial damage is affected.

Helicobacter pylori manipulates cancer-related signal transduction events in infected gastric epithelial cells such as the phosphorylation status of the actin-binding protein cortactin and cortactin overexpression by about 2–3 fold. Cortactin overexpression depends on the integrity of the type IV secretion system and the translocated effector protein CagA. We propose that overexpression of cortactin is based both on upregulated mRNA expression and enhanced protein stability requiring the indicated pathways to mitogen-activated protein kinase JNK, paxillin, FAK and others, which together may have an impact on gastric cancer development.

• Brucella abortus infection upregulates galectin-3 expression
• Galectin-3 modulates proinflammatory cytokine production during bacterial infection
• Galectin-3 favours Brucella replication

Salmonella strains were engineered to report, on level of single intracellular bacteria, their intracellular niche and the availability of inorganic phosphate (P_i). In the Salmonella-containing vacuole (SCV), P_i is limited and limitation increases with bacterial proliferation. Salmonella located in host cell cytosol are not limited in P_i availability. Remodelling of the host cell endosomal system mediated by T3SS-2 reliefs P_i limitation in the SCV.

Scanning electron microscopy (SEM) analysis of the effects of syncollin-Strep on bacterial structure. Bacteria were incubated in either buffer alone or in buffer containing syncollin-Strep (0.3 mg/ml) before SEM imaging. Scale bar, 1 μm.

Inflammasome signalling during group A Streptococcus infection is an emerging field of research. Multiple virulence factors activate the NLRP3 inflammasome, including streptolysin O, streptolysin S, SpyA and M protein, whilst the protease SpeB contributes to the maturation of IL-1β independently of the inflammasome pathway. IL-1β signalling can be host-protective, but also drive severe GAS disease.

The phosphorylation at residue 227 of MoSom1 is essential for infection-related infection-related development and plant infection in Magnaporthe oryzae. In addition, phosphorylation of MoSom1 at serine-227 is important for the activation of Pmk1.

Candidalysin, a potent cytotoxin secreted by the invasive form of the human pathogenic fungus Candida albicans, is capable of inducing necrotic cell death in epithelial cells. Candidalysin remains at the host epithelial cell membrane and causes an increase in the intracellular calcium (Ca²⁺) concentration, mitochondrial membrane dysfunction (Δψm), production of reactive oxygen species (ROS) and adenosine triphosphate (ATP) depletion. Candidalysin-induced epithelial cell death is accompanied by loss of plasma membrane integrity followed by cytoplasmic leakage.

A genome-wide siRNA screen identified 321 human genes that enhance Dot/Icm effector translocation by Legionella pneumophila. Hit analysis implicated host cell ubiquitination factors in the efficiency of Dot/Icm effector translocation. Two host proteins, UBE2E1 and CUL7, localised to the Legionella containing vacuole and enhanced L. pneumophila intracellular replication.