Chlamydia trachomatis is a major human pathogen responsible for the most prevalent bacterial sexually transmitted infections. Given its high prevalence, potential for serious complications and high economic burden, understanding the pathogenesis of C. trachomatis infections is crucial for developing effective prevention and treatment strategies. Mucosal epithelial cells serve as the primary replicative niche and play a central role in infection. Historically, research has relied heavily on cancer-derived cell line models to study the interactions ofC. trachomatis with host cells. Although these models have provided important insights, they fail to fully recapitulate key aspects of human physiology, including apical-basal polarity, a fundamental feature that shapes epithelial functions. Limited studies using polarized in vitro epithelial systems have uncovered unique mechanisms by which C. trachomatis interacts with host cells. In this review, we summarize the current, albeit limited, knowledge on the role of epithelial polarity during C. trachomatis infection and highlight this understudied aspect of chlamydial biology.

Intracellular Gram-negative pathogens employ either type IVA or type IVB secretion systems (T4SSs) to translocate effector proteins into host cells, where they modulate cellular processes to facilitate infection and promote intracellular survival. Roughly one-third of these effectors harbor hydrophobic transmembrane domains and are thus destined for integration into host cell membranes during infection. Many of these transmembrane domain-containing effectors (TMEs) localize to the membrane of the pathogen-containing vacuole, thereby contributing to its formation and remodeling. Despite the biological relevance of TMEs, the detailed molecular mechanisms governing their translocation via T4SSs and subsequent membrane integration in the host cell remain insufficiently understood. In this review, the biophysical characteristics of T4SS-secreted TMEs are systematically examined, including predictions of membrane topology and hydrophobicity. These analyses are then contextualized through comparison with recent structural analysis of both T4ASS and T4BSS machineries, as well as with mechanistic principles of eukaryotic membrane protein biogenesis. This integrative approach enables the conceptual reconstruction of the potential pathways by which TMEs are translocated through the T4SS and subsequently targeted and inserted into host membranes, offering new mechanistic insights into the poorly understood handling of bacterial TMEs from both the pathogen and host perspectives.

Candida albicans is a leading cause of invasive candidiasis, a life-threatening infection with high mortality despite antifungal therapy. Echinocandins are first-line agents due to their fungicidal activity and low toxicity profile. Beyond direct killing, they may also modulate host immunity, e.g. through fungal cell wall remodeling. However, the systemic impact of echinocandins on human immune cells remains incompletely understood, particularly in the context of drug resistance. Using an ex vivo human whole-blood infection model, we assessed the effects of caspofungin during infection with echinocandin-susceptible (ECHS/FKSwt) and echinocandin-resistant (ECHR/FKSmut) C. albicans strains. Infection alone triggered a strong and conserved transcriptional immune program enriched for innate recognition and inflammatory pathways. Caspofungin treatment during infection with the susceptible strain selectively amplified these responses, engaging a sequential cascade of host defenses that linked pathogen recognition with innate effector functions and adaptive polarisation. In contrast, caspofungin induced only minimal transcriptional changes in resistant strain infections or in uninfected blood. These findings demonstrate that caspofungin efficacy arises not only from its fungicidal activity but also from amplification of host immunity, an effect primarily dependent on fungal susceptibility. This dual mode of action highlights a previously underappreciated role of echinocandins in shaping antifungal immunity and provides new mechanistic insight into drug-host–pathogen interactions during systemic candidiasis.

Protists, which comprise the majority of eukaryotic diversity, frequently engage in endosymbiotic relationships with other unicellular eukaryotes or prokaryotes. These interactions have profoundly shaped eukaryotic evolution, not only through the origin of endosymbiotic organelles and the subsequent diversification of eukaryotes, but also via less studied endosymbioses that have influenced the evolution of diverse eukaryotic lineages. Endosymbioses often alter host metabolic capabilities, enabling the colonisation of new ecological niches and significantly contributing to ecosystem functioning. In recent years, interest in these interactions has increased, driven by methodological innovations and new discoveries that reveal the diversity, mechanisms, and ecological roles of protist endosymbioses. Despite these advances, key questions remain: How widespread and ecologically impactful are protist endosymbioses? What functions do symbionts provide, and how do associations form, persist, or break down? Addressing these questions requires systematic studies of protists in their natural environments, combining microscopy and sequencing using both high-throughput and single-cell approaches, along with experimental manipulations of host-symbiont interactions. Here, we review current knowledge, highlight recent breakthroughs, and discuss ongoing challenges in the study of protist endosymbioses.

Prokaryotic microorganisms coexist with mobile genetic elements (MGEs), which can be both genetic threats and evolutionary catalysts. In Haloferax lucentense, a halophilic archaeon, we have recently identified an unusual genomic arrangement: a complete type I-B CRISPR-Cas system encoded on a megaplasmid and an incomplete type I–B system within an integrated provirus in the main chromosome. The provirus-encoded system lacks the adaptation genes (cas1, cas2, and cas4), suggesting its potential reliance on the megaplasmid-encoded CRISPR-Cas module for the acquisition of new spacers. This arrangement suggests a potential instance of “adaptive outsourcing,” where a provirus might leverage a co-resident MGE for a key function. Through comparative genomics, we show that similar proviral CRISPR-Cas systems are found in distantly related haloarchaea (e.g. Natrinema and Halobacterium), indicating probable virus-mediated horizontal transfer and suggesting they may function as mobile defense modules. Phylogenetic analysis highlights distinct evolutionary origins of the two systems: the plasmid system clusters with other Haloferax CRISPR-Cas systems, while the proviral system clusters with those from other genera, consistent with horizontal acquisition. Interestingly, spacer analysis reveals that the proviral systems predominantly target viral sequences, while the plasmid system appears to target both plasmids and viral sequences, a distribution mirroring broader trends observed in other plasmid- and chromosome-encoded CRISPR systems. This observed targeting preference suggests a potential for complementarity that could support a model of cooperative immunity, where each system may protect its genetic “owner” from competition and, indirectly, the host.

International audience

The 2024 International Union of Microbiological Societies Congress was held in Florence, the city of Renaissance. The theme was to increase the awareness of the power of microbial life, recognizing that it can lead the transformation towards a sustainable planet. The meeting gathered over 1400 experts from more than 90 countries and focused on the transformative potential of microbiology in addressing global challenges and aligning microbial science with the Sustainable Development Goals. Six roundtable discussions explored the pivotal role of microbiology in mitigating climate change, preparing for pandemics, producing sustainable energy, promoting a One Health approach, understanding microbiome dynamics, and developing data infrastructure. The discussions revealed that microbes are still overlooked agents in sustainable solutions. Expert panellists at the roundtables discussed microbial innovations in hydrogen and biofuel production, conversion of greenhouse gases, biomanufacturing, and soil restoration, the role of microbiome in immune health, the importance of cross-kingdom interactions, and the integration of food, environmental, and microbiomes under the One Health framework. Panels stressed the need for equitable access to vaccines, diagnostics, and data sharing, especially in the face of antimicrobial resistance. The importance of global collaboration, data repositories, and regulatory alignment, was repeatedly emphasized. The congress invited calls for the formation of an international microbiology coalition, need for interdisciplinary partnerships, increased investment in microbial technologies, updating of regulatory frameworks, and integration of microbiome science into public health and environmental policy. Microorganisms are the oldest architects of nature, able to build a sustainable future for the planet.

Respiratory syncytial virus (RSV), a negative-sense single-stranded RNA virus of the Pneumoviridae family, represents the most important pathogen of lower respiratory tract infections in young infants causing yearly epidemics. RSV is also an important respiratory viral pathogen for older subjects, which is second only to seasonal influenza virus infections. RSV represents a substantial public health burden with respect to morbidity and mortality, particularly in developing countries. Prevention and treatment options would therefore lessen the global disease burden. A formalin-inactivated RSV vaccine in the 1960s induced an enhanced disease upon exposure to natural RSV. After this tragical vaccine failure, it took nearly five decades of intensive research before prevention tools were approved by health authorities. The lead was taken by passive immunity approaches with injected monoclonal antibodies directed against the fusion protein F of RSV. The elucidation of the three-dimensional structure of the F protein revealed pre- and postfusion conformations. Subsequently, structure-based antigen engineering of the F protein paved the way for development of a prophylactic vaccine. In 2023, RSV vaccines were approved for maternal vaccination to protect young infants by placental transfer of antibodies and for vaccination in older subjects. Antiviral drugs that target the RSV fusion process, the RSV replicase, or the cytoplasmic viral factories are in development. Important research papers leading to these developments are reviewed here.

Bacterial small proteins impact diverse physiological processes, however, technical challenges posed by small size hampered their systematic identification and biochemical characterization. In our quest to uncover small proteins relevant for Salmonella pathogenicity, we previously identified YjiS, a 54 amino acid protein, which is strongly induced during this pathogen’s intracellular infection stage. Here, we set out to further characterize the role of YjiS. Cell culture infection assays with Salmonella mutants lacking or overexpressing YjiS suggested this small protein to delay bacterial escape from macrophages. Mutant scanning of the protein’s conserved, arginine-rich DUF1127 domain excluded a major effect of single amino acid substitutions on the infection phenotype. A comparative dual RNA-seq assay uncovered the molecular footprint of YjiS in the macrophage response to infection, with host effects related to oxidative stress and the cell cortex. Bacterial cell fractionation experiments demonstrated YjiS to associate with the inner membrane and proteins interacting with YjiS in pull-down experiments were enriched for inner membrane processes. Among the YjiS interactors was the two-component system SsrA/B, the master transcriptional activator of intracellular virulence genes and a suppressor of flagellar genes. Indeed, in the absence of YjiS, we observed elevated expression of motility genes and an increased number of flagella per bacterium. Together, our study points to a role for Salmonella YjiS as a membrane-associated timer of pathogen dissemination.

The ongoing arms race between bacteria and phages has forced bacteria to evolve a sophisticated set of antiphage defense mechanisms that constitute the bacterial immune system. In our previous study, we highlighted the antiphage properties of aminoglycoside antibiotics, which are naturally secreted by Streptomyces. Successful inhibition of phage infection was achieved by addition of pure compounds and supernatants from a natural producer strain emphasizing the potential for community-wide antiphage defense. However, given the dual functionality of these compounds, neighboring bacterial cells require resistance to the antibacterial activity of aminoglycosides to benefit from the protection they confer against phages. In this study, we tested a variety of different aminoglycoside resistance mechanisms acting via drug or target (16S rRNA) modification and demonstrated that they do not interfere with the antiphage properties of the molecules. Furthermore, we confirmed the antiphage impact of aminoglycosides in a community context by coculturing phage-susceptible, apramycin-resistant Streptomyces venezuelae with the apramycin-producing strain Streptoalloteichus tenebrarius. Given the prevalence of aminoglycoside resistance among natural bacterial isolates, this study highlights the ecological relevance of chemical defense via aminoglycosides at the community level.