The adult phenotype of mosquitoes depends on the types of bacteria encountered environmentally during development.

Highlights d The susceptibility of CD4 + T cell subsets to HIV-1 matches their metabolic activity d HIV-1 selectively infects CD4 + T cells with enhanced glycolysis and OXPHOS d Inhibition of metabolic activities blocks HIV-1 replication d Suboptimal inhibition of glycolysis impairs amplification of HIV-1 reservoirs

Listeria monocytogenes is responsible for gastroenteritis in healthy individuals and for a severe invasive disease in immunocompromised patients. Among the three identified L. monocytogenes evolutionary lineages, lineage I strains are overrepresented in epidemic listeriosis outbreaks, but the mechanisms underlying the higher virulence potential of strains of this lineage remain elusive. Here, we demonstrate that Listeriolysin S (LLS), a virulence factor only present in a subset of lineage I strains, is a bacteriocin highly expressed in the intestine of orally infected mice that alters the host intestinal microbiota and promotes intestinal colonization by L. monocytogenes, as well as deeper organ infection. To our knowledge, these results therefore identify LLS as the first bacteriocin described in L. monocytogenes and associate modulation of host microbiota by L. monocytogenes epidemic strains to increased virulence.T he gram-positive bacterium Listeria monocytogenes is a facultative intracellular pathogen that causes foodborne infections in humans and animals. Upon consumption of contaminated food, L. monocytogenes reaches the intestinal lumen, crosses the intestinal barrier, and disseminates within the host. The clinical manifestations of listeriosis vary from a mild, self-limiting gastroenteritis to severe intestinal and systemic infections, with a fatality rate estimated to 20-30% of infected individuals (1). Host gut microbiota plays a critical role in resistance against colonization by invading pathogens within the intestine (2). The mechanisms of L. monocytogenes to compete with the host microbiota to survive in the intestine remain unknown.During the last decades, the majority of Listeria studies in bacterial pathophysiology, cell biology, and immunology compared three pathogenic strains from lineage II: EGD, EGD-e, and 10403S (3). Interestingly, major listeriosis epidemics have been preferentially associated to L. monocytogenes clonal groups belonging to the evolutionary lineage I and, more specifically, to serotype 4b (4, 5), but the molecular mechanisms that contribute to the higher virulence potential of these bacterial strains have not been identified yet.Bacteriocins are bacterially synthesized proteinaceous substances that target and inhibit the growth of closely related bacteria, allowing competition in diverse ecological niches, including the digestive tract (6, 7). Production of these antimicrobial peptides is widespread among bacterial species, and such production is made possible by biosynthetic machineries present in the genome, plasmids, or conjugative transposons (7). A conserved biosynthetic gene cluster for the production of bacteriocins displaying thiazole and oxazole heterocycles was discovered in 2008 in six microbial phyla (8). These gene clusters encode a toxin precursor and all indispensable proteins for toxin maturation in a mode similar to that associated with the bacteriocin microcin B17 (8). This gene cluster in L .monocytogenes was only present in a subset of lineage I strains...

Nature MetabolisM T cells ex vivo can be isolated from HICs but not from cART individuals 8,10,18 (Fig. 1a). In the present study, it was first investigated whether this capacity of HIC CD8 + T cells could be found among naive, central memory, transitional memory and effector memory CD8 + T cell subsets (see Supplementary Fig. 1). As expected, naive CD8 + T cells from HICs had no HIV-suppressive capacity. In contrast, all sorted memory CD8 + T cell subsets from HICs, but not from cART individuals, suppressed HIV infection as efficiently as bulk CD8 + T cells (Fig. 1b). Therefore, although effector memory cells probably had more immediate antiviral capacity 12 , HIVspecific CD8 + TCMs from HICs can efficiently react to counteract HIV-1 infection during co-culture. These results support the view that the strong antiviral potential of HICs is already embedded in the programme of their HIV-specific CD8 + TCMs. Distinct gene expression profile in HIV-specific CD8 + TCMs from HICs. A comparison was then made of the single-cell gene expression profiles (96 genes associated with CD8 + T cell function, differentiation, metabolism and survival (see Supplementary Fig. 2 and Supplementary Data 1) of HIV-specific CD8 + TCMs from five HICs whose CD8 + T cells had strong HIV-suppressive capacity and from five cART individuals (see Supplementary Table 1). Cells from cART individuals and HICs analysed in the present study shared not only the same differentiation status but also the same activation phenotype, as defined by flow cytometry (Fig. 1c and see Supplementary Table 2). Despite their similar phenotype, t-SNE (t-distributed stochastic neighbour-embedding algorithm)-based

SummaryUropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections (UTIs) worldwide, causing over 150 million clinical cases annually. There is currently no specific treatment addressing the asymptomatic carriage in the gut of UPEC before they initiate UTIs. This study investigates the efficacy of virulent bacteriophages to decrease carriage of gut pathogens. Three virulent bacteriophages infecting an antibiotic-resistant UPEC strain were isolated and characterized both in vitro and in vivo. A new experimental murine model of gut carriage of E. coli was elaborated and the impact of virulent bacteriophages on colonization levels and microbiota diversity was assessed. A single dose of a cocktail of the three bacteriophages led to a sharp decrease in E. coli levels throughout the gut. We also observed that microbiota diversity was much less affected by bacteriophages than by antibiotics. Therefore, virulent bacteriophages can efficiently target UPEC strains residing in the gut, with potentially profound public health and economic impacts. These results open a new area with the possibility to manipulate specifically the microbiota using virulent bacteriophages, which could have broad applications in many gut-related disorders/diseases and beyond.

BackgroundHost-associated microbes, collectively known as the microbiota, play an important role in the biology of multicellular organisms. In mosquito vectors of human pathogens, the gut bacterial microbiota influences vectorial capacity and has become the subject of intense study. In laboratory studies of vector biology, genetic effects are often inferred from differences between geographically and genetically diverse colonies of mosquitoes that are reared in the same insectary. It is unclear, however, to what extent genetic effects can be confounded by uncontrolled differences in the microbiota composition among mosquito colonies. To address this question, we used 16S metagenomics to compare the midgut bacterial microbiome of six laboratory colonies of Aedes aegypti recently derived from wild populations representing the geographical range and genetic diversity of the species.ResultsWe found that the diversity, abundance, and community structure of the midgut bacterial microbiome was remarkably similar among the six different colonies of Ae. aegypti, regardless of their geographical origin. We also confirmed the relatively low complexity of bacterial communities inhabiting the mosquito midgut.ConclusionsOur finding that geographically diverse colonies of Ae. aegypti reared in the same insectary harbor a similar gut bacterial microbiome supports the conclusion that the gut microbiota of adult mosquitoes is environmentally determined regardless of the host genotype. Thus, uncontrolled differences in microbiota composition are unlikely to represent a significant confounding factor in genetic studies of vector biology.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-2780-1) contains supplementary material, which is available to authorized users.

Metabolically quiescent pathogens can persist in a viable non-replicating state for months or even years. For certain infectious diseases, such as tuberculosis, cryptococcosis, histoplasmosis, latent infection is a corollary of this dormant state, which has the risk for reactivation and clinical disease. During murine cryptococcosis and macrophage uptake, stress and host immunity induce Cryptococcus neoformans heterogeneity with the generation of a sub-population of yeasts that manifests a phenotype compatible with dormancy (low stress response, latency of growth). In this subpopulation, mitochondrial transcriptional activity is regulated and this phenotype has been considered as a hallmark of quiescence in stem cells. Based on these findings, we worked to reproduce this phenotype in vitro and then standardize the experimental conditions to consistently generate this dormancy in C . neoformans . We found that incubation of stationary phase yeasts (STAT) in nutriment limited conditions and hypoxia for 8 days (8D-HYPOx) was able to produced cells that mimic the phenotype obtained in vivo . In these conditions, mortality and/or apoptosis occurred in less than 5% of the yeasts compared to 30–40% of apoptotic or dead yeasts upon incubation in normoxia (8D-NORMOx). Yeasts in 8D-HYPOx harbored a lower stress response, delayed growth and less that 1% of culturability on agar plates, suggesting that these yeasts are viable but non culturable cells (VBNC). These VBNC were able to reactivate in the presence of pantothenic acid, a vitamin that is known to be involved in quorum sensing and a precursor of acetyl-CoA. Global metabolism of 8D-HYPOx cells showed some specific requirements and was globally shut down compared to 8D-NORMOx and STAT conditions. Mitochondrial analyses showed that the mitochondrial mass increased with mitochondria mostly depolarized in 8D-HYPOx compared to 8D-NORMox, with increased expression of mitochondrial genes. Proteomic and transcriptomic analyses of 8D-HYPOx revealed that the number of secreted proteins and transcripts detected also decreased compared to 8D-NORMOx and STAT, and the proteome, secretome and transcriptome harbored specific profiles that are engaged as soon as four days of incubation. Importantly, acetyl-CoA and the fatty acid pathway involving mitochondria are required for the generation and viability maintenance of VBNC. Altogether, these data show that we were able to generate for the first time VBNC phenotype in C . neoformans . This VBNC state is associated with a specific metabolism that should be further studied to understand dormancy/quiescence in this yeast.

Motivation: With the continued improvement of requisite mass spectrometers and UHPLC systems, Hydrogen/Deuterium eXchange Mass Spectrometry (HDX-MS) workflows are rapidly evolving towards the investigation of more challenging biological systems, including large protein complexes and membrane proteins. The analysis of such extensive systems results in very large HDX-MS datasets for which specific analysis tools are required to speed up data validation and interpretation.Results: We introduce a web application and a new R-package named ‘MEMHDX’ to help users analyze, validate and visualize large HDX-MS datasets. MEMHDX is composed of two elements. A statistical tool aids in the validation of the results by applying a mixed-effects model for each peptide, in each experimental condition, and at each time point, taking into account the time dependency of the HDX reaction and number of independent replicates. Two adjusted P-values are generated per peptide, one for the ‘Change in dynamics’ and one for the ‘Magnitude of ΔD’, and are used to classify the data by means of a ‘Logit’ representation. A user-friendly interface developed with Shiny by RStudio facilitates the use of the package. This interactive tool allows the user to easily and rapidly validate, visualize and compare the relative deuterium incorporation on the amino acid sequence and 3D structure, providing both spatial and temporal information.Availability and Implementation: MEMHDX is freely available as a web tool at the project home page http://memhdx.c3bi.pasteur.frContact: marie-agnes.dillies@pasteur.fr or sebastien.brier@pasteur.frSupplementary information: Supplementary data is available at Bioinformatics online.