Microbiology and Infectious Disease

eLife assessment

This study defines a fundamental aspect of protein kinase signalling in the protist parasite Toxoplasma gondii that is required for acute and chronic infections. The authors provide compelling evidence for the role of SPARK/SPARKEL kinases in regulating cAMP/cGMP signalling, although evidence linking the loss of these kinases to changes in the phosphoproteome is incomplete. Overall, this study will be of great interest to those who study Toxoplasma and related apicomplexan parasites.

eLife assessment

This important research uses an elegant combination of protein-protein biochemistry, genetics, and microscopy to demonstrate that the novel bacterial protein FipA is required for polar flagella synthesis and binds to FlhF in multiple bacterial species. This manuscript is convincing, providing evidence for the early stages of flagellar synthesis at a cell pole; however, the protein biochemistry is incomplete and would benefit from additional rigorous experiments. This paper could be of significant interest to microbiologists studying bacterial motility, appendages, and cellular biology.

eLife assessment

The work by Han and collaborators describes valuable findings on the role of Akkermansia muciniphila during ETEC infection. If confirmed, these findings will add to a growing list of beneficial properties of this organism. However, as it stands, the strength of the evidence used to justify the conclusions in the manuscript is incomplete.

eLife assessment

This important study furthers our understanding of the antimicrobial properties of siderophores, and their potential use to battle opportunistic pathogens. The evidence supporting the conclusion is solid, based on rigorous biochemical, growth, and virulence assays. The work would benefit from a more in-depth discussion of the consequences and efficacy of 'siderophore therapy' in more complex communities/environments. The work will be of broad interest to colleagues in the fields of evolutionary ecology, microbiology, and medical sciences.

eLife assessment

This work uses an interdisciplinary approach combining microfluidics, structural biology, and genetic analyses to provide important findings that show that pathogenic enteric bacteria exhibit taxis toward human serum. The data are compelling and show that the behavior utilizes the bacterial chemotaxis system and the chemoreceptor Tsr, which senses the amino acid L-serine. The work provides an ecological context for the role of serine as a bacterial chemoattractant and could have clinical implications for bacterial bloodstream invasion during episodes of gastrointestinal bleeding.

eLife assessment

In this manuscript, the authors investigate whether the effects of the BCG vaccine on immunity to Mtb infection could be improved by inhibiting amidation of the peptidoglycan sidechains to allow for recognition by NOD-1. This is a very important area and an interesting new approach to improve vaccination for TB. The authors find that CRISPRi knockdown of murT-gatD causes rather dramatic cell wall defects, more accessible cell wall labeling, and results in attenuated growth in macrophages and mice. This forms a foundation for further study of whether an approach like that which is presented herein would improve vaccination responses in TB.

eLife assessment

Urtecho et al. use genome-integrated massively parallel reporter assays to catalog and characterize promoters throughout the Escherichia coli genome. The result is a state-of-the-art atlas of promoters, coupled with information on their regulation, that is readily accessible through the website http://ecolipromoterdb.com. This compelling work provides an important resource for researchers studying bacterial transcriptional regulation.

eLife assessment

Sulphur atoms derived from cysteine are thought to play significant roles in maintaining redox homeostasis in Mycobacterium tuberculosis, which encounters stresses associated with immune cell interactions. In this valuable manuscript, the authors provide solid evidence that the genes encoding cysteine biosynthetic enzymes (cysM and cysK2) are required to maintain full viability of M. tuberculosis under in vitro stress conditions, macrophage infections, and within the lung tissues of mice. The manuscript presents transcriptomic and metabolomic evidence to support the hypothesis that CysM and CysK2 play distinct roles in maintaining cysteine-derived metabolite pools under stress conditions. The work will be of interest to microbiologists in general.

eLife assessment

This useful study describes a single set of label-chase mass spectrometry experiments to confirm the molecular function of YafK as a peptidoglycan hydrolase, and to describe the timing of its attachment to the peptidoglycan. Confirmation of the molecular function of YafK will be helpful in further studies to examine the function and regulation of the outer membrane-peptidoglycan link in bacteria. The evidence supporting the molecular function of YafK and that lpp molecules are shuffled on and off the peptidoglycan is solid, however, data supporting conclusions relating to the locations of lpp-peptidoglycan attachment are incomplete. The work will be of interest to microbiologists studying the bacterial cell wall.

eLife assessment

This important study identifies differential Orsay virus infection of C. elegans when animals are fed on different bacteria. The evidence for this is however, incomplete, as experiments to control for feeding rate and bacterial pathogenicity are needed as well as direct quantification of viral load.

eLife assessment

This important work provides a detailed analysis of the population dynamics of an important human bacterial pathogen, Neisseria gonorrhoeae, using a large global collection of genomes with geographic, temporal, and demographic metadata. A unique facet of this work is the focus on both importation and exportation of N. gonorrhoeae; whilst quantifying importation is important to national public health efforts, quantifying exportation is relevant on an international level. However, the evidence supporting the conclusions is incomplete, due to potential inaccuracies in the method used for phylogenetic analysis, which forms the basis of this work. With the phylogenetic analysis strengthened, this paper would be of interest to epidemiologists and public health officials working on N. gonorrhoeae epidemiology and interventions.

eLife assessment

This valuable study underscores the significance of PfMORC in shaping chromatin and guiding transitions in the malaria parasite, Plasmodium falciparum, that are essential for its survival. Solid evidence reveals PfMORC's influence on genes related to antigenic variation and the parasite's lifecycle, marking PfMORC as a key regulator of parasite heterochromatin.

eLife assessment

This important study combines experimental infections with laboratory and field Plasmodium falciparum isolates to quantify the force of human malaria parasite transmission. By using compelling methodological approaches, the authors establish clear positive correlations between mosquito infection levels (as determined by oocyst numbers), sporozoite loads in salivary glands, and sporozoites expelled during feeding. The link between heterogenous infection levels in the mosquitoes and malaria transmission would be of interest to vector biologists, parasitologists, immunologists, and mathematical modellers.

eLife assessment

This study provides valuable insights into how chromatin-bound PfMORC controls gene expression in the asexual blood stage of Plasmodium falciparum. By interacting with key nuclear proteins, PfMORC appears to affect expression of genes relating to host invasion and subtelomeric var genes. Correlating transcriptomic data with in vivo chromatin insights, the study provides solid evidence for the central role of PfMORC in epigenetic transcriptional regulation through modulation of chromatin compaction.

eLife assessment

This important study demonstrates widespread introgression between species of cyanobacteria in hot springs in Yellowstone National Park. Using single cell sequencing of hundreds of genomes, the authors provide one of the most convincing demonstrations to date of the importance of selection and hybridization in shaping polymorphism within a natural community. The strong enthusiasm for the paper is only dampened slightly by the methods not being described in the clearest possible manner.

eLife assessment

This potentially useful study aims to advance our understanding of the structure of the native form of a viral toxin secreted from infected cells. While some of the findings confirm previous reports, the new claims in this study are unfortunately only inadequately supported by the methods and analyses used. More rigorous approaches are needed to justify the main conclusion that the structure of the viral toxin derived from infected cells in this study is distinct from previously reported structures of recombinantly expressed versions of the toxin.

eLife assessment

This is a valuable report that describes that ACE2 expression is upregulated by SARS-CoV-2 infection via activation of transcription factor Sp1 and inhibition of HNF4α through the PI3K/AKT pathway. Inhibition of Sp1 reduces SARS-CoV-2 infection in vitro and in an animal model. This work is solid and will be of interest to those interested in ACE2 biology and its impact in COVID-19.

eLife assessment

This paper reports useful findings regarding gut bacteria that metabolize dietary flavonoids, which can enhance, reduce, or otherwise alter the flavonoid bioactivities. With a newly developed bioinformatics tool, the authors predict bacterial species that can metabolize parts of the flavonoid tilianin. Formal proof of concept is missing, but if experimentally confirmed, the study will change the way we think about metabolism of flavonoids and would be of broad interest regarding gut bacterial metabolism. Most of the analyses are compelling, but others require further inquiry.

eLife assessment

This valuable study combines in vitro and in vivo experiments designed to test if a deoxycytidine kinase inhibitor provides therapeutic benefit during infection with Staphylococcus aureus. The authors provide compelling evidence that this putative host-directed therapy has good potential to promote natural clearance of infection without targeting the bacterium. This paper would be of interest to bacteriologists, immunologists, and those studying host-microbe interactions.

eLife assessment

This important study demonstrates that disrupting a common protein-folding system restores sensitivity to antibiotics in drug-resistant clinical bacterial pathogens. Although some additional controls would be welcome, the work is overall convincing in showing that targeting protein folding can be used to combat multi-drug resistant pathogens, both by potentiating the efficacy of existing drugs and by therapeutic use of small-molecule inhibitors. This study is significant and timely as it furnishes a new strategy that is relevant to microbiologists and clinicians interested in combating antimicrobial resistance.