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Life in extreme environments : insights in biological capability
\"From deep ocean trenches and the geographical poles to outer space, organisms can be found living in remarkably extreme conditions. This book provides a captivating account of these systems and their extraordinary inhabitants, 'extremophiles'. A diverse, multidisciplinary group of experts discuss responses and adaptations to change; biodiversity, bioenergetic processes, and biotic and abiotic interactions; polar environments; and life and habitability, including searching for biosignatures in the extraterrestrial environment. The editors emphasize that understanding these systems is important for increasing our knowledge and utilizing their potential, but this remains an understudied area. Given the threat to these environments and their biota caused by climate change and human impact, this timely book also addresses the urgency to document these systems. It will help graduate students and researchers in conservation, marine biology, evolutionary biology, environmental change and astrobiology better understand how life exists in these environments and their susceptibility or resilience to change\"-- Provided by publisher.
Book
Conjugative DNA Transfer Induces the Bacterial SOS Response and Promotes Antibiotic Resistance Development through Integron Activation
Conjugation is one mechanism for intra- and inter-species horizontal gene transfer among bacteria. Conjugative elements have been instrumental in many bacterial species to face the threat of antibiotics, by allowing them to evolve and adapt to these hostile conditions. Conjugative plasmids are transferred to plasmidless recipient cells as single-stranded DNA. We used lacZ and gfp fusions to address whether conjugation induces the SOS response and the integron integrase. The SOS response controls a series of genes responsible for DNA damage repair, which can lead to recombination and mutagenesis. In this manuscript, we show that conjugative transfer of ssDNA induces the bacterial SOS stress response, unless an anti-SOS factor is present to alleviate this response. We also show that integron integrases are up-regulated during this process, resulting in increased cassette rearrangements. Moreover, the data we obtained using broad and narrow host range plasmids strongly suggests that plasmid transfer, even abortive, can trigger chromosomal gene rearrangements and transcriptional switches in the recipient cell. Our results highlight the importance of environments concentrating disparate bacterial communities as reactors for extensive genetic adaptation of bacteria.
Journal Article
The hidden half of nature : the microbial roots of life and health
\"Prepare to set aside what you think you know about yourself and microbes. Good health--for people and for plants--depends on Earth's smallest creatures. [This book] tells the story of our tangled relationship with microbes and their potential to revolutionize agriculture and medicine, from garden to gut\"--Dust jacket flap.
BOOK
Repeat Rifaximin for Irritable Bowel Syndrome: No Clinically Significant Changes in Stool Microbial Antibiotic Sensitivity
Background
Rifaximin has demonstrated efficacy and safety for diarrhea-predominant irritable bowel syndrome (IBS-D).
Aim
To determine the rifaximin repeat treatment effect on fecal bacterial antibiotic susceptibility.
Methods
Patients with IBS in Trial 3 (TARGET 3) study who responded to open-label rifaximin 550 mg three times daily for 2 weeks, with symptom recurrence within 18 weeks, were randomized to double-blind treatment: two 2-week repeat courses of rifaximin or placebo, separated by 10 weeks. Prospective stool sample collection occurred before and after open-label rifaximin, before and after the first repeat course, and at the end of the study. Susceptibility testing was performed with 11 antibiotics, including rifaximin and rifampin, using broth microdilution or agar dilution methods.
Results
Of 103 patients receiving open-label rifaximin, 73 received double-blind rifaximin (
n
= 37) or placebo (
n
= 36). A total of 1429 bacterial and yeast isolates were identified, of which Bacteroidaceae (36.7%) and Enterobacteriaceae (33.9%) were the most common. In the double-blind phase,
Clostridium difficile
was highly susceptible to rifaximin [minimum inhibitory concentration (MIC) range 0.008–1 µg/mL] and rifampin (MIC range 0.004–0.25 µg/mL). Following double-blind rifaximin treatment,
Staphylococcus
isolates remained susceptible to rifaximin at all visits (MIC
50
range ≤0.06–32 µg/mL). Rifaximin exposure was not associated with long-term cross-resistance of Bacteroidaceae, Enterobacteriaceae, and Enterococcaceae to rifampin or nonrifamycin antibiotics tested.
Conclusions
In this study, short-term repeat treatment with rifaximin has no apparent long-term effect on stool microbial susceptibility to rifaximin, rifampin, and nonrifamycin antibiotics.
ClinicalTrials.gov Identifier
NCT01543178.
Journal Article
Metabolic dependencies drive species co-occurrence in diverse microbial communities
Microbial communities populate most environments on earth and play a critical role in ecology and human health. Their composition is thought to be largely shaped by interspecies competition for the available resources, but cooperative interactions, such as metabolite exchanges, have also been implicated in community assembly. The prevalence of metabolic interactions in microbial communities, however, has remained largely unknown. Here, we systematically survey, by using a genome-scale metabolic modeling approach, the extent of resource competition and metabolic exchanges in over 800 communities. We find that, despite marked resource competition at the level of whole assemblies, microbial communities harbor metabolically interdependent groups that recur across diverse habitats. By enumerating flux-balanced metabolic exchanges in these co-occurring subcommunities we also predict the likely exchanged metabolites, such as amino acids and sugars, that can promote group survival under nutritionally challenging conditions. Our results highlight metabolic dependencies as a major driver of species co-occurrence and hint at cooperative groups as recurring modules of microbial community architecture.
Significance Although metabolic interactions have long been implicated in the assembly of microbial communities, their general prevalence has remained largely unknown. In this study, we systematically survey, by using a metabolic modeling approach, the extent of resource competition and metabolic cross-feeding in over 800 microbial communities from diverse habitats. We show that interspecies metabolic exchanges are widespread in natural communities, and that such exchanges can provide group advantage under nutrient-poor conditions. Our results highlight metabolic dependencies as a major driver of species co-occurrence. The presented methodology and mechanistic insights have broad implications for understanding compositional variation in natural communities as well as for facilitating the design of synthetic microbial communities.
Journal Article
Characterization of Yeast Extracellular Vesicles: Evidence for the Participation of Different Pathways of Cellular Traffic in Vesicle Biogenesis
Extracellular vesicles in yeast cells are involved in the molecular traffic across the cell wall. In yeast pathogens, these vesicles have been implicated in the transport of proteins, lipids, polysaccharide and pigments to the extracellular space. Cellular pathways required for the biogenesis of yeast extracellular vesicles are largely unknown.
We characterized extracellular vesicle production in wild type (WT) and mutant strains of the model yeast Saccharomyces cerevisiae using transmission electron microscopy in combination with light scattering analysis, lipid extraction and proteomics. WT cells and mutants with defective expression of Sec4p, a secretory vesicle-associated Rab GTPase essential for Golgi-derived exocytosis, or Snf7p, which is involved in multivesicular body (MVB) formation, were analyzed in parallel. Bilayered vesicles with diameters at the 100-300 nm range were found in extracellular fractions from yeast cultures. Proteomic analysis of vesicular fractions from the cells aforementioned and additional mutants with defects in conventional secretion pathways (sec1-1, fusion of Golgi-derived exocytic vesicles with the plasma membrane; bos1-1, vesicle targeting to the Golgi complex) or MVB functionality (vps23, late endosomal trafficking) revealed a complex and interrelated protein collection. Semi-quantitative analysis of protein abundance revealed that mutations in both MVB- and Golgi-derived pathways affected the composition of yeast extracellular vesicles, but none abrogated vesicle production. Lipid analysis revealed that mutants with defects in Golgi-related components of the secretory pathway had slower vesicle release kinetics, as inferred from intracellular accumulation of sterols and reduced detection of these lipids in vesicle fractions in comparison with WT cells.
Our results suggest that both conventional and unconventional pathways of secretion are required for biogenesis of extracellular vesicles, which demonstrate the complexity of this process in the biology of yeast cells.
Journal Article
Integrated network analysis reveals the importance of microbial interactions for maize growth
milk*Microbes play a critical role in soil global biogeochemical circulation and microbe–microbe interactions have also evoked enormous interests in recent years. Utilization of green manures can stimulate microbial activity and affect microbial composition and diversity. However, few studies focus on the microbial interactions or detect the key functional members in communities. With the advances of metagenomic technologies, network analysis has been used as a powerful tool to detect robust interactions between microbial members. Here, random matrix theory-based network analysis was used to investigate the microbial networks in response to four different green manure fertilization regimes (Vicia villosa, common vetch, milk vetch, and radish) over two growth cycles from October 2012 to September 2014. The results showed that the topological properties of microbial networks were dramatically altered by green manure fertilization. Microbial network under milk vetch amendment showed substantially more intense complexity and interactions than other fertilization systems, indicating that milk vetch provided a favorable condition for microbial interactions and niche sharing. The shift of microbial interactions could be attributed to the changes in some major soil traits and the interactions might be correlated to plant growth and production. With the stimuli of green manures, positive interactions predominated the network eventually and the network complexity was in consistency with maize productivity, which suggested that the complex soil microbial networks might benefit to plants rather than simple ones, because complex networks would hold strong the ability to cope with environment changes or suppress soil-borne pathogen infection on plants. In addition, network analyses discerned some putative keystone taxa and seven of them had directly positive interactions with maize yield, which suggested their important roles in maintaining environmental functions and in improving plant growth.
Journal Article
Optimising trial designs to identify appropriate antibiotic treatment durations
Background
For many infectious conditions, the optimal antibiotic course length remains unclear. The estimation of course length must consider the important trade-off between maximising short- and long-term efficacy and minimising antibiotic resistance and toxicity.
Main body
Evidence on optimal treatment durations should come from randomised controlled trials. However, most antibiotic randomised controlled trials compare two arbitrarily chosen durations. We argue that alternative trial designs, which allow allocation of patients to multiple different treatment durations, are needed to better identify optimal antibiotic durations. There are important considerations when deciding which design is most useful in identifying optimal treatment durations, including the ability to model the duration–response relationship (or duration–response ‘curve’), the risk of allocation concealment bias, statistical efficiency, the possibility to rapidly drop arms that are clearly inferior, and the possibility of modelling the trade-off between multiple competing outcomes.
Conclusion
Multi-arm designs modelling duration–response curves with the possibility to drop inferior arms during the trial could provide more information about the optimal duration of antibiotic therapies than traditional head-to-head comparisons of limited numbers of durations, while minimising the probability of assigning trial participants to an ineffective treatment regimen.
Journal Article
BacArena: Individual-based metabolic modeling of heterogeneous microbes in complex communities
Recent advances focusing on the metabolic interactions within and between cellular populations have emphasized the importance of microbial communities for human health. Constraint-based modeling, with flux balance analysis in particular, has been established as a key approach for studying microbial metabolism, whereas individual-based modeling has been commonly used to study complex dynamics between interacting organisms. In this study, we combine both techniques into the R package BacArena (https://cran.r-project.org/package=BacArena) to generate novel biological insights into Pseudomonas aeruginosa biofilm formation as well as a seven species model community of the human gut. For our P. aeruginosa model, we found that cross-feeding of fermentation products cause a spatial differentiation of emerging metabolic phenotypes in the biofilm over time. In the human gut model community, we found that spatial gradients of mucus glycans are important for niche formations which shape the overall community structure. Additionally, we could provide novel hypothesis concerning the metabolic interactions between the microbes. These results demonstrate the importance of spatial and temporal multi-scale modeling approaches such as BacArena.
Journal Article
The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives
ABSTRACT
Candida albicans is a major fungal pathogen of humans. It exists as a commensal in the oral cavity, gut or genital tract of most individuals, constrained by the local microbiota, epithelial barriers and immune defences. Their perturbation can lead to fungal outgrowth and the development of mucosal infections such as oropharyngeal or vulvovaginal candidiasis, and patients with compromised immunity are susceptible to life-threatening systemic infections. The importance of the interplay between fungus, host and microbiota in driving the transition from C. albicans commensalism to pathogenicity is widely appreciated. However, the complexity of these interactions, and the significant impact of fungal, host and microbiota variability upon disease severity and outcome, are less well understood. Therefore, we summarise the features of the fungus that promote infection, and how genetic variation between clinical isolates influences pathogenicity. We discuss antifungal immunity, how this differs between mucosae, and how individual variation influences a person's susceptibility to infection. Also, we describe factors that influence the composition of gut, oral and vaginal microbiotas, and how these affect fungal colonisation and antifungal immunity. We argue that a detailed understanding of these variables, which underlie fungal-host-microbiota interactions, will present opportunities for directed antifungal therapies that benefit vulnerable patients.
The complexity and variability of FunHoMic interactions between the fungal pathogen, its human host and the Microbiota strongly influence the development and outcomes of the superficial and systemic Candida albicans infections that plague human health worldwide.
Journal Article