An Aerobic Exercise: Defining the Roles of Pseudomonas aeruginosa Terminal Oxidases

The opportunistic pathogen Pseudomonas aeruginosa encodes a large and diverse complement of aerobic terminal oxidases, which is thought to contribute to its ability to thrive in settings with low oxygen availability. In this issue, Arai et al. (J. Bacteriol. 196:4206 – 4215, 2014, doi:http://dx.doi.org/10.1128/JB.02176-14) present a thorough characterization of these five complexes, enabling a more detailed understanding of aerobic respiration in this organism

An orphan cbb3-type cytochrome oxidase subunit supports Pseudomonas aeruginosa biofilm growth and virulence

Hypoxia is a common challenge faced by bacteria during associations with hosts due in part to the formation of densely packed communities (biofilms). cbb3-type cytochrome c oxidases, which catalyze the terminal step in respiration and have a high affinity for oxygen, have been linked to bacterial pathogenesis. The pseudomonads are unusual in that they often contain multiple full and partial (i.e. ‘orphan’) operons for cbb3-type oxidases and oxidase subunits. Here, we describe a unique role for the orphan catalytic subunit CcoN4 in colony biofilm development and respiration in the opportunistic pathogen Pseudomonas aeruginosa PA14. We also show that CcoN4 contributes to the reduction of phenazines, antibiotics that support redox balancing for cells in biofilms, and to virulence in a Caenorhabditis elegans model of infection. These results highlight the relevance of the colony biofilm model to pathogenicity and underscore the potential of cbb3-type oxidases as therapeutic targets

Stream Members Only: Data-Driven Characterization of Stellar Streams with Mixture Density Networks

Stellar streams are sensitive probes of the Milky Way's gravitational potential. The mean track of a stream constrains global properties of the potential, while its fine-grained surface density constrains galactic substructure. A precise characterization of streams from potentially noisy data marks a crucial step in inferring galactic structure, including the dark matter, across orders of magnitude in mass scales. Here we present a new method for constructing a smooth probability density model of stellar streams using all of the available astrometric and photometric data. To characterize a stream's morphology and kinematics, we utilize mixture density networks to represent its on-sky track, width, stellar number density, and kinematic distribution. We model the photometry for each stream as a single-stellar population, with a distance track that is simultaneously estimated from the stream's inferred distance modulus (using photometry) and parallax distribution (using astrometry). We use normalizing flows to characterize the distribution of background stars. We apply the method to the stream GD-1, and the tidal tails of Palomar 5. For both streams we obtain a catalog of stellar membership probabilities that are made publicly available. Importantly, our model is capable of handling data with incomplete phase-space observations, making our method applicable to the growing census of Milky Way stellar streams. When applied to a population of streams, the resulting membership probabilities from our model form the required input to infer the Milky Way's dark matter distribution from the scale of the stellar halo down to subhalos.Comment: 35 pages, 13 figures, 4 tables, fully open-source and reproducible using ShowYourWor

Horizontal gene transfer as a source of conflict and cooperation in prokaryotes

Horizontal gene transfer (HGT) is one of the most important processes in prokaryote evolution. The sharing of DNA can spread neutral or beneficial genes, as well as genetic parasites across populations and communities, creating a large proportion of the variability acted on by natural selection. Here, we highlight the role of HGT in enhancing the opportunities for conflict and cooperation within and between prokaryote genomes. We discuss how horizontally acquired genes can cooperate or conflict both with each other and with a recipient genome, resulting in signature patterns of gene co-occurrence, avoidance, and dependence. We then describe how interactions involving horizontally transferred genes may influence cooperation and conflict at higher levels (populations, communities, and symbioses). Finally, we consider the benefits and drawbacks of HGT for prokaryotes and its fundamental role in understanding conflict and cooperation from the gene-gene to the microbiome level

Management and Outcome of 64 Patients with Pancreatic Serous Cystic Neoplasms

Background: The optimal management approach to pancreatic serous cystic neoplasms (SCNs) is still evolving. Methods: Consecutive patients with SCN managed at the Liverpool Pancreas Cancer Centre between 2000 and 2013 were retrospectively reviewed. Results: There were 64 patients consisting of 39 women (60.9%) and 25 men (39.1%). Forty-seven patients (73.4%) had surgical removal and 17 (26.6%) were observed. The possibility of a non-SCN malignancy was the predominant indication for resection in 27 (57.4%) patients. Postoperative morbidity occurred in 26 (55.3%) patients with 2 (4.3%) deaths. An increased risk of resection was associated with patient's age (p = 0.011), diagnosis before 2009 (p < 0.001), pain (p = 0.043), possibility of cancer (p = 0.009) and a solid SCN component on imaging (p = 0.002). Independent factors associated with resection were a diagnosis before 2009 (p = 0.005) and a solid SCN component (p < 0.001). Independent factors associated with shorter time to surgical resection were persistent pain (p = 0.003) and a solid SCN component (p = 0.007). Conclusion: There was a reduction in the proportion of resections with the application of an observe-only policy for asymptomatic patients with more definite features of SCN. Improved criteria are still required in the remainder of patients with uncertain features of SCN in deciding for intervention or surveillance

The gut microbiota of siblings offers insights into microbial pathogenesis of inflammatory bowel disease

Siblings of patients with Crohn's disease (CD) have elevated risk of developing CD and display aspects of disease phenotype, including faecal dysbiosis. In our recent article we have used 16S rRNA gene targeted high-throughput sequencing to comprehensively characterize the mucosal microbiota in healthy siblings of CD patients, and determine the influence of genotypic and phenotypic factors on the gut microbiota (dysbiosis). We have demonstrated that the core microbiota of both patients with CD and healthy siblings is significantly less diverse than controls. Faecalibacterium prausnitzii contributed most to core metacommunity dissimilarity between both patients and controls and between siblings and controls. Phenotype/genotype markers of CD risk significantly influenced microbiota variation between and within groups, of which genotype had the largest effect. Individuals with elevated CD-risk display mucosal dysbiosis characterized by reduced diversity of core microbiota and lower abundance of F. prausnitzii. The presence of this dysbiosis in healthy people at-risk of CD implicates microbiological processes in CD pathogenesis

Siblings of Crohn's Disease Patients Exhibit a Pathologically Relevant Dysbiosis: Examination of Mucosal Microbiota Communities Using 16S rRNA Gene Pyrosequencing

Background Reduced mucosal concentrations of Faecalibacterium prausnitzii predict disease recurrence in patients with Crohn's disease (CD). Siblings of CD patients have elevated risk of developing CD and share aspects of disease phenotype compared with healthy controls (HC), including dysbiosis in the faecal microbiota.[1] No study has compared the mucosal microbiota of CD siblings with unrelated healthy controls. Aim: to determine whether dysbiosis is present in the mucosal microbiota of siblings of CD patients with reference to HC, and to apply 16S rRNA gene pyrosequencing in order to accomplish a more comprehensive characterisation of that dysbiosis. Methods Rectal biopsies were taken from 21 patients with quiescent CD, 17 of their healthy siblings and 19 unrelated HC. Total DNA was extracted using phenol/chloroform based method. The V1 to V3 region of the bacterial 16S ribosomal RNA gene was amplified using PCR, and microbiota composition resolved by 454 pyrosequencing. Sequence processing and analyses were performed using the open source Mothur software package (www.mothur.org). Results For each group the resulting species in the microbiota were classified into core (common and abundant among similar subjects) versus infrequent and rare.[2] In terms of both microbial diversity (measured by both the ShannonWiener and Simpson's indexes of diversity) and species richness, the core mucosal microbiota of both siblings and CD patients were significantly less diverse than HC. Although the diversity of the rare microbiota was lower in CD compared with HC, there was no difference in diversity of rare microbiota between siblings and HC. Metacommunity profiling using the Bray-Curtis (SBC) index of similarity with unweighted pair group averages showed that the core microbial metacommunity of siblings was more similar to CD (SBC=0.70) than to HC, whereas the rare microbial metacommunity of siblings was more similar to HC (SBC= 0.42). As in CD patients, the species that contributed most to the dissimilarity between healthy siblings and HC was F. prausnitzii, Table 1. Conclusions This is the first in depth case-control study of the mucosal microbiota in the siblings of CD patients. We report a dysbiosis characterised by reduced diversity of core microbiota and lower abundance of F. prausnitzii. Given that siblings of CD patients have elevated risk of developing CD, this dysbiosis in otherwise healthy people implicates microbiological processes in CD pathogenesis and risk