Microbiology and Infectious Disease

eLife assessment

This important study points out discrepancies between the clinical diagnosis of Clostridioides difficile infection and the lack of detectable C. difficile in gut microbiome samples, as well as different relationships between asymptomatic C. difficile carriage and adult or infant gut microbiota compositions. While the solid analysis of a comprehensive and diverse metagenomic dataset suggests an over-diagnosis of C. difficile infection and an under-diagnosis of other putative enteric pathogens, the work requires addressing the detection limitations of the approach to be more convincing. This work will interest microbiologists and clinicians concerned with understanding the role of C. difficile in gut microbiota health and dysbiosis.

eLife assessment

This elegantly performed and rigorous study generates new and conceptually important insights into the interaction between an essential malaria parasite invasion ligand (and vaccine candidate) called PfRH5, and its erythrocyte surface integral membrane receptor basigin. The authors provide compelling evidence based on rigorous biochemical assays that erythrocyte basigin is predominantly expressed in a complex with one of two distinct erythrocyte membrane proteins called PMCA and MCT1 and that PfRH5 binds to these complexes better than to isolated basigin. Certain invasion-inhibitory antibodies, that do not prevent binding of PfRH5 to isolated basigin, do in contrast prevent binding to the basigin complexes, explaining the mode of action of these previously enigmatic antibodies and providing valuable data towards the improved design of vaccines based on PfRH5.

eLife assessment

This study has uncovered some interesting findings about the fungal composition and its interaction with bacteria in Caesarean section scar diverticulum (CSD). While the study's findings are valuable and with translation possibilities, the strength of the conclusions obtained is incomplete due to the small sample size and methodological issues indicated by the reviewers such as the lack of controls and the location of samples analyzed.

eLife assessment

This study describes an important bioinformatics tool for normalizing gene copy number from metagenomic assemblies. The tool is used in a meta-analysis of data from inflammatory bowel disease (IBD) patients and healthy controls. While some of the evidence for the power of the method is compelling, other evidence seems incomplete. The inclusion of additional computational and/or experimental validation would markedly strengthen the study. This paper will likely be of broad interest to researchers studying the role of complex microbial communities in host health and disease.

eLife assessment

This valuable study presents an exhaustive structural analysis of a complete tripartite HipBST toxin-antitoxin system of the Enteropathogenic E. coli O127:H6, which represents a fascinating variation on the well-studied HipAB toxin-antitoxin system. The convincing data show that major features of the canonical HipAB system have been rerouted to form the tripartite HipBST, revealing a new mode of inhibition of a toxin kinase.

eLife assessment

This important study advances the understanding of physiological mechanisms in deep-sea Planctomycetes bacteria, revealing unique characteristics such as the only known Phycisphaerae using a budding mode of division, extensive involvement in nitrate assimilation and release phage particles without cell death. The study uses convincing evidence, based on experiments using growth assays, phylogenetics, transcriptomics, and gene expression data. The work will be of interest to bacteriologists and microbiologists in general.

eLife assessment

This work presents valuable information about the specificity and promiscuity of toxic effector and immunity protein pairs. The evidence supporting the claims of the authors is currently incomplete, as there is concern about the methodology used to analyze protein interactions, which did not take potential differences in expression levels, protein folding, and/or transient interaction into account. Other methods to measure the strength of interactions and structural predictions would improve the study. The work will be of interest to microbiologists and biochemists working with toxin-antitoxin and effector-immunity proteins.

eLife assessment

This important paper provides insights into the role of the inflammasomes in the control of Salmonella replication within human macrophages. Solid evidence is provided that in the absence of inflammasome signaling that Salmonella replicated in the macrophage cytosol. This paper will be of broad interest to cell biologists, immunologists and microbiologists.

eLife assessment

This is an important study that tries to shed light on why the deer mouse is host to many diverse pathogens. The results are convincing and rely on state of the art transcriptomic analysis. The findings will be of interest to the biologists, ecologists and infectious disease researchers.

eLife assessment

This study presents valuable findings on Legionella pneumophila effector proteins that target host vesicle trafficking GTPases during infection and more specifically modulate ubiquitination of the host GTPase Rab10. The evidence supporting the claims of the authors is solid, although it remains unclear how modification of the GTPase Rab10 with ubiquitin supports Legionella virulence and the impact of ubiquitination during LCV formation. The work will be of interest to colleagues studying animal pathogens as well as cell biologists in general.

eLife assessment

Resistance of Plasmodium falciparum to artemisinin, which has become a threat to malaria control, has been linked to mutations in the parasite protein K13. This study provides important new insights into the function of K13 in the endocytosis of hemoglobin, a central process for the activation of artemisinin derivatives. Conditional protein mislocalization combined with high-resolution imaging provides convincing evidence that K13 is involved in the formation of cytostomes, the structures involved in the endocytosis of host cytosol. This study will be of interest to scientists working on parasite biology as well as antimalarial drug resistance.

eLife assessment

The valuable study by Dumeaux et al examines the transcriptional response to antifungal treatment in the major opportunistic human fungal pathogen Candida albicans. Using solid methodology, including a novel droplet-based single cell transcriptomics platform, the authors report that fungal cells exhibit heterogeneity in their transcriptional response to antifungal drug treatment. The ability to study the trajectories of individual cells in a high-throughput manner provides a novel perspective on studying the emergence of drug tolerance and resistance in fungal pathogens.

eLife assessment

This study addresses an important question in the field of antimicrobial chemotherapy: whether combinations of enzyme inhibitors that select for mutations that confer resistance to one inhibitor and at the same time increased sensitization to the other inhibitor can provide a path towards mitigating resistance risks. The authors here investigated one such combination of inhibitors of Plasmodium falciparum DHODH (dihydroorotate dehydrogenase), finding that despite "collateral sensitivity", it was still possible to select a mutation that mediated resistance to both inhibitors without any change in parasite fitness. Additional cross-susceptibility and structural modeling strengthen this study, which is performed to a high technical standard and presents a convincing body of data.

eLife assessment

This important study uses near full-length HIV-1 sequencing to examine proviral persistence in various tissues derived from three individuals who received antiretroviral therapy until time of death. Intact as well as defective HIV-1 proviruses are found at various anatomical sites including the central nervous system; the results are convincing and relevant for our understanding of latent viral reservoirs, especially in the brain.

eLife assessment

This important study helps to elucidate the mechanism by which the agr quorum-sensing system in Staphylococcus aureus contributes to virulence. The results are supported by solid evidence using state-of-the-art methods. The linkage of metabolism and virulence in this pathogen will be of interest to the areas of microbiology, infectious diseases and immunology.

eLife assessment

Salmonella invades and survives in host cells via SPI-1 and SPI-2 type III secretion system mechanisms, with the SPI-2 system allowing for intracellular survival in Salmonella-containing vacuoles, which have a low-pH environment. Transcription of SPI-2 genes at low pH is activated by the DNA-binding SsrB protein, which sits at the top of the SPI-2 regulatory hierarchy. This study provides important insights as to how SsrB is allosterically affected by pH resulting in acid-dependent DNA binding. However, there are concerns about some experiments, and the evidence presented is not fully conclusive.

eLife assessment

This useful manuscript describes the TOR signaling pathway in the human and plant pathogen Aspergillus flavus. While the authors provide a large amount of descriptive and often confirmative data, the evidence for the new claims made here for the TOR pathway in this species is incomplete.

eLife assessment

Trypanosoma brucei evades mammalian humoral immunity through the expression of different variant surface glycoprotein genes. In this fundamental paper, the authors extend previous observations that TbRAP1 both interacts with PIP5Pase and binds PI(3,4,5)P3, indicating a role for PI(3,4,5)P3 binding and suggesting that antigen switching is signal dependent. While much of the evidence is compelling, the work would benefit from further controls to rule out that any of the observed effects come from the protein tags used.

eLife assessment

This valuable study describes engineered dengue virus variants that can be used to dissect epitope specificities in polyclonal sera, and to design candidate vaccine antigens that dampen antibody responses against undesirable epitopes. While the major claims are supported by solid evidence, experiments to distinguish the impact on antibody binding from neutralizing activities would have strengthened the study. This work will be of interest to virologists and structural biologists working on antibody responses to flaviviruses.

eLife assessment

This important paper reports a novel, compelling method, based on barcoding viral genes and next-generation sequencing, to quantify both viral transcription levels and progeny virus production in influenza virus-infected cells at the single-cell level. The authors show that viral transcription and progeny virus production are unexpectedly poorly correlated, and that cells in which viral RNAs are transcribed at high levels are not necessarily those producing the most progeny virions. Because of its novelty, the study will be of interest to the broader virology community.