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‣ The Turbulent Network Dynamics of Microbial Evolution and the Statistical Tree of Life

Koonin, Eugene V.
Fonte: Springer US Publicador: Springer US
Tipo: Artigo de Revista Científica
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The wide spread and high rate of gene exchange and loss in the prokaryotic world translate into “network genomics”. The rates of gene gain and loss are comparable with the rate of point mutations but are substantially greater than the duplication rate. Thus, evolution of prokaryotes is primarily shaped by gene gain and loss. These processes are essential to prevent mutational meltdown of microbial populations by stopping Muller’s ratchet and appear to trigger emergence of major novel clades by opening up new ecological niches. At least some bacteria and archaea seem to have evolved dedicated devices for gene transfer. Despite the dominance of gene gain and loss, evolution of genes is intrinsically tree-like. The significant coherence between the topologies of numerous gene trees, particularly those for (nearly) universal genes, is compatible with the concept of a statistical tree of life, which forms the framework for reconstruction of the evolutionary processes in the prokaryotic world.

‣ Within and between Whorls: Comparative Transcriptional Profiling of Aquilegia and Arabidopsis

Voelckel, Claudia; Borevitz, Justin O.; Hodges, Scott A.; Baxter, Ivan; Kramer, Elena M.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Background: The genus Aquilegia is an emerging model system in plant evolutionary biology predominantly because of its wide variation in floral traits and associated floral ecology. The anatomy of the Aquilegia flower is also very distinct. There are two whorls of petaloid organs, the outer whorl of sepals and the second whorl of petals that form nectar spurs, as well as a recently evolved fifth whorl of staminodia inserted between stamens and carpels. Methodology/Principal Findings: We designed an oligonucleotide microarray based on EST sequences from a mixed tissue, normalized cDNA library of an A. formosa x A. pubescens F2 population representing 17,246 unigenes. We then used this array to analyze floral gene expression in late pre-anthesis stage floral organs from a natural A. formosa population. In particular, we tested for gene expression patterns specific to each floral whorl and to combinations of whorls that correspond to traditional and modified ABC model groupings. Similar analyses were performed on gene expression data of Arabidopsis thaliana whorls previously obtained using the Ath1 gene chips (data available through The Arabidopsis Information Resource). Conclusions/Significance: Our comparative gene expression analyses suggest that 1) petaloid sepals and petals of A. formosa share gene expression patterns more than either have organ-specific patterns...

‣ Methylobacterium Genome Sequences: A Reference Blueprint to Investigate Microbial Metabolism of C1 Compounds from Natural and Industrial Sources

Vuilleumier, Stéphane; Chistoserdova, Ludmila; Bringel, Françoise; Lajus, Aurélie; Gourion, Benjamin; Barbe, Valérie; Chang, Jean; Cruveiller, Stéphane; Dossat, Carole; Gillett, Will; Gruffaz, Christelle; Haugen, Eric; Hourcade, Edith; Levy, Ruth; Ma
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Methylotrophy describes the ability of organisms to grow on reduced organic compounds without carbon-carbon bonds. The genomes of two pink-pigmented facultative methylotrophic bacteria of the Alpha-proteobacterial genus Methylobacterium, the reference species Methylobacterium extorquens strain AM1 and the dichloromethane-degrading strain DM4, were compared. Methodology/Principal Findings The 6.88 Mb genome of strain AM1 comprises a 5.51 Mb chromosome, a 1.26 Mb megaplasmid and three plasmids, while the 6.12 Mb genome of strain DM4 features a 5.94 Mb chromosome and two plasmids. The chromosomes are highly syntenic and share a large majority of genes, while plasmids are mostly strain-specific, with the exception of a 130 kb region of the strain AM1 megaplasmid which is syntenic to a chromosomal region of strain DM4. Both genomes contain large sets of insertion elements, many of them strain-specific, suggesting an important potential for genomic plasticity. Most of the genomic determinants associated with methylotrophy are nearly identical, with two exceptions that illustrate the metabolic and genomic versatility of Methylobacterium. A 126 kb dichloromethane utilization (dcm) gene cluster is essential for the ability of strain DM4 to use DCM as the sole carbon and energy source for growth and is unique to strain DM4. The methylamine utilization (mau) gene cluster is only found in strain AM1...

‣ Pneumococcal Capsular Polysaccharide Structure Predicts Serotype Prevalence

Weinberger, Daniel M.; Trzciński, Krzysztof; Bogaert, Debby; Brandes, Aaron; Lu, Ying-Jie; Galagan, James E; Anderson, Porter; Malley, Richard; Lipsitch, Marc
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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There are 91 known capsular serotypes of Streptococcus pneumoniae. The nasopharyngeal carriage prevalence of particular serotypes is relatively stable worldwide, but the host and bacterial factors that maintain these patterns are poorly understood. Given the possibility of serotype replacement following vaccination against seven clinically important serotypes, it is increasingly important to understand these factors. We hypothesized that the biochemical structure of the capsular polysaccharides could influence the degree of encapsulation of different serotypes, their susceptibility to killing by neutrophils, and ultimately their success during nasopharyngeal carriage. We sought to measure biological differences among capsular serotypes that may account for epidemiological patterns. Using an in vitro assay with both isogenic capsule-switch variants and clinical carriage isolates, we found an association between increased carriage prevalence and resistance to non-opsonic neutrophil-mediated killing, and serotypes that were resistant to neutrophil-mediated killing tended to be more heavily encapsulated, as determined by FITC-dextran exclusion. Next, we identified a link between polysaccharide structure and carriage prevalence. Significantly...

‣ Comparative ICE Genomics: Insights into the Evolution of the SXT/R391 Family of ICEs

Wozniak, Rachel A. F.; Fouts, Derrick E.; Spagnoletti, Matteo; Colombo, Mauro M.; Ceccarelli, Daniela; Garriss, Geneviève; Déry, Christine; Burrus, Vincent; Waldor, Matthew K.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Integrating and conjugative elements (ICEs) are one of the three principal types of self-transmissible mobile genetic elements in bacteria. ICEs, like plasmids, transfer via conjugation; but unlike plasmids and similar to many phages, these elements integrate into and replicate along with the host chromosome. Members of the SXT/R391 family of ICEs have been isolated from several species of gram-negative bacteria, including Vibrio cholerae, the cause of cholera, where they have been important vectors for disseminating genes conferring resistance to antibiotics. Here we developed a plasmid-based system to capture and isolate SXT/R391 ICEs for sequencing. Comparative analyses of the genomes of 13 SXT/R391 ICEs derived from diverse hosts and locations revealed that they contain 52 perfectly syntenic and nearly identical core genes that serve as a scaffold capable of mobilizing an array of variable DNA. Furthermore, selection pressure to maintain ICE mobility appears to have restricted insertions of variable DNA into intergenic sites that do not interrupt core functions. The variable genes confer diverse element-specific phenotypes, such as resistance to antibiotics. Functional analysis of a set of deletion mutants revealed that less than half of the conserved core genes are required for ICE mobility; the functions of most of the dispensable core genes are unknown. Several lines of evidence suggest that there has been extensive recombination between SXT/R391 ICEs...

‣ Genetic Diversity among Enterococcus faecalis

McBride, Shonna M.; Fischetti, Vincent A.; LeBlanc, Donald J.; Moellering, Robert Charles; Gilmore, Michael S.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Enterococcus faecalis, a ubiquitous member of mammalian gastrointestinal flora, is a leading cause of nosocomial infections and a growing public health concern. The enterococci responsible for these infections are often resistant to multiple antibiotics and have become notorious for their ability to acquire and disseminate antibiotic resistances. In the current study, we examined genetic relationships among 106 strains of E. faecalis isolated over the past 100 years, including strains identified for their diversity and used historically for serotyping, strains that have been adapted for laboratory use, and isolates from previously described E. faecalis infection outbreaks. This collection also includes isolates first characterized as having novel plasmids, virulence traits, antibiotic resistances, and pathogenicity island (PAI) components. We evaluated variation in factors contributing to pathogenicity, including toxin production, antibiotic resistance, polymorphism in the capsule (cps) operon, pathogenicity island (PAI) gene content, and other accessory factors. This information was correlated with multi-locus sequence typing (MLST) data, which was used to define genetic lineages. Our findings show that virulence and antibiotic resistance traits can be found within many diverse lineages of E. faecalis. However...

‣ High-Throughput, Kingdom-Wide Prediction and Annotation of Bacterial Non-Coding RNAs

Teonadi, Hidayat; Livny, Miron; Livny, Jonathan; Waldor, Matthew K
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Background: Diverse bacterial genomes encode numerous small non-coding RNAs (sRNAs) that regulate myriad biological processes. While bioinformatic algorithms have proven effective in identifying sRNA-encoding loci, the lack of tools and infrastructure with which to execute these computationally demanding algorithms has limited their utilization. Genome-wide predictions of sRNA-encoding genes have been conducted in less than 3% of all sequenced bacterial strains, leading to critical gaps in current annotations. The relative paucity of genome-wide sRNA prediction represents a critical gap in current annotations of bacterial genomes and has limited examination of larger issues in sRNA biology, such as sRNA evolution. Methodology/Principal Findings: We have developed and deployed SIPHT, a high throughput computational tool that utilizes workflow management and distributed computing to effectively conduct kingdom-wide predictions and annotations of intergenic sRNA-encoding genes. Candidate sRNA-encoding loci are identified based on the presence of putative Rho-independent terminators downstream of conserved intergenic sequences, and each locus is annotated for several features, including conservation in other species, association with one of several transcription factor binding sites and homology to any of over 300 previously identified sRNAs and cis-regulatory RNA elements. Using SIPHT...

‣ ElaD, a Deubiquitinating Protease Expressed by E. Coli

Misaghi, Shahram; Korbel, Gregory A.; Ploegh, Hidde L.; Catic, Andre
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Background: Ubiquitin and ubiquitin-like proteins (Ubl) are designed to modify polypeptides in eukaryotes. Covalent binding of ubiquitin or Ubls to substrate proteins can be reversed by specific hydrolases. One particular set of cysteine proteases, the CE clan, which targets ubiquitin and Ubls, has homologs in eukaryotes, prokaryotes, and viruses. Findings: We have cloned and analyzed the E. coli protein elaD, which is distantly related to eukaryotic CE clan members of the ULP/SENP protease family that are specific for SUMO and Nedd8. Previously misannotated as a putative sulfatase/phosphatase, elaD is an efficient and specific deubiquitinating enzyme in vitro. Interestingly, elaD is present in all intestinal pathogenic E. coli strains, but conspicuously absent from extraintestinal pathogenic strains (ExPECs). Further homologs of this protease can be found in Acanthamoeba Polyphaga Mimivirus, and in Alpha-, Beta-and Gammaproteobacteria. Conclusion: The expression of ULP/SENP-related hydrolases in bacteria therefore extends to plant pathogens and medically relevant strains of Escherichia coli, Legionella pneumophila, Rickettsiae, Chlamydiae, and Salmonellae, in which the elaD ortholog sseL has recently been identified as a virulence factor with deubiquitinating activity. As a counterpoint...

‣ Mobile Antibiotic Resistance Encoding Elements Promote Their Own Diversity

Garriss, Geneviève; Burrus, Vincent; Rosenberg, Susan M.; Waldor, Matthew K
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Integrating conjugative elements (ICEs) are a class of bacterial mobile genetic elements that disseminate via conjugation and then integrate into the host cell genome. The SXT/R391 family of ICEs consists of more than 30 different elements that all share the same integration site in the host chromosome but often encode distinct properties. These elements contribute to the spread of antibiotic resistance genes in several gram-negative bacteria including Vibrio cholerae, the agent of cholera. Here, using comparative analyses of the genomes of several SXT/R391 ICEs, we found evidence that the genomes of these elements have been shaped by inter–ICE recombination. We developed a high throughput semi-quantitative method to explore the genetic determinants involved in hybrid ICE formation. Recombinant ICE formation proved to be relatively frequent, and to depend on host (recA) and ICE (s065 and s066) loci, which can independently and potentially cooperatively mediate hybrid ICE formation. s065 and s066, which are found in all SXT/R391 ICEs, are orthologues of the bacteriophage λ Red recombination genes bet and exo, and the s065/s066 recombination system is the first Red-like recombination pathway to be described in a conjugative element. Neither ICE excision nor conjugative transfer proved to be essential for generation of hybrid ICEs. Instead conjugation facilitates the segregation of hybrids and could provide a means to select for functional recombinant ICEs containing novel combinations of genes conferring resistance to antibiotics. Thus...

‣ Quantitative deep sequencing reveals dynamic HIV-1 escape and large population shifts during CCR5 antagonist therapy in vivo

Korber, Bette; Russ, Carsten; Lo, Chien-Chi; Leitner, Thomas; Gaschen, Brian; Theiler, James; Paredes, Roger; Su, Zhaohui; Gulick, Roy M.; Greaves, Wayne; Coakley, Eoin; Flexner, Charles; Nusbaum, Chad; Tsibris, Athe Michael Noel; Arnaout, Ramy; Hughes, M
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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High-throughput sequencing platforms provide an approach for detecting rare HIV-1 variants and documenting more fully quasispecies diversity. We applied this technology to the V3 loop-coding region of env in samples collected from 4 chronically HIV-infected subjects in whom CCR5 antagonist (vicriviroc [VVC]) therapy failed. Between 25,000–140,000 amplified sequences were obtained per sample. Profound baseline V3 loop sequence heterogeneity existed; predicted CXCR4-using populations were identified in a largely CCR5-using population. The V3 loop forms associated with subsequent virologic failure, either through CXCR4 use or the emergence of high-level VVC resistance, were present as minor variants at 0.8–2.8% of baseline samples. Extreme, rapid shifts in population frequencies toward these forms occurred, and deep sequencing provided a detailed view of the rapid evolutionary impact of VVC selection. Greater V3 diversity was observed post-selection. This previously unreported degree of V3 loop sequence diversity has implications for viral pathogenesis, vaccine design, and the optimal use of HIV-1 CCR5 antagonists.

‣ Evidence of Molecular Evolution Driven by Recombination Events Influencing Tropism in a Novel Human Adenovirus that Causes Epidemic Keratoconjunctivitis

Walsh, Michael P.; Chintakuntlawar, Ashish; Harrach, Balázs; Hudson, Nolan R.; Schnurr, David; Heim, Albert; Seto, Donald; Jones, Morris S.; Robinson, Christopher; Madisch, Ijad; Chodosh, James
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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In 2005, a human adenovirus strain (formerly known as HAdV-D22/H8 but renamed here HAdV-D53) was isolated from an outbreak of epidemic keratoconjunctititis (EKC), a disease that is usually caused by HAdV-D8, -D19, or -D37, not HAdV-D22. To date, a complete change of tropism compared to the prototype has never been observed, although apparent recombinant strains of other viruses from species Human adenovirus D (HAdV-D) have been described. The complete genome of HAdV-D53 was sequenced to elucidate recombination events that lead to the emergence of a viable and highly virulent virus with a modified tropism. Bioinformatic and phylogenetic analyses of this genome demonstrate that this adenovirus is a recombinant of HAdV-D8 (including the fiber gene encoding the primary cellular receptor binding site), HAdV-D22, (the ε determinant of the hexon gene), HAdV-D37 (including the penton base gene encoding the secondary cellular receptor binding site), and at least one unknown or unsequenced HAdV-D strain. Bootscanning analysis of the complete genomic sequence of this novel adenovirus, which we have re-named HAdV-D53, indicated at least five recombination events between the aforementioned adenoviruses. Intrahexon recombination sites perfectly framed the ε neutralization determinant that was almost identical to the HAdV-D22 prototype. Additional bootscan analysis of all HAdV-D hexon genes revealed recombinations in identical locations in several other adenoviruses. In addition...

‣ Evolution under Fluctuating Environments Explains Observed Robustness in Metabolic Networks

Soyer, Orkun S.; Pfeiffer, Thomas
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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A high level of robustness against gene deletion is observed in many organisms. However, it is still not clear which biochemical features underline this robustness and how these are acquired during evolution. One hypothesis, specific to metabolic networks, is that robustness emerges as a byproduct of selection for biomass production in different environments. To test this hypothesis we performed evolutionary simulations of metabolic networks under stable and fluctuating environments. We find that networks evolved under the latter scenario can better tolerate single gene deletion in specific environments. Such robustness is underlined by an increased number of independent fluxes and multifunctional enzymes in the evolved networks. Observed robustness in networks evolved under fluctuating environments was “apparent,” in the sense that it decreased significantly as we tested effects of gene deletions under all environments experienced during evolution. Furthermore, when we continued evolution of these networks under a stable environment, we found that any robustness they had acquired was completely lost. These findings provide evidence that evolution under fluctuating environments can account for the observed robustness in metabolic networks. Further...

‣ Recognition of HIV-1 Peptides by Host CTL Is Related to HIV-1 Similarity to Human Proteins

Rolland, Morgane; Nickle, David C.; Deng, Wenjie; Frahm, Nicole; Learn, Gerald H.; Heckerman, David; Jojic, Nebosja; Jojic, Vladimir; Mullins, James I.; Brander, Christian; Walker, Bruce David
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Background: While human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes preferentially target specific regions of the viral proteome, HIV-1 features that contribute to immune recognition are not well understood. One hypothesis is that similarities between HIV and human proteins influence the host immune response, i.e., resemblance between viral and host peptides could preclude reactivity against certain HIV epitopes. Methodology/Principal Findings: We analyzed the extent of similarity between HIV-1 and the human proteome. Proteins from the HIV-1 B consensus sequence from 2001 were dissected into overlapping k-mers, which were then probed against a non-redundant database of the human proteome in order to identify segments of high similarity. We tested the relationship between HIV-1 similarity to host encoded peptides and immune recognition in HIV-infected individuals, and found that HIV immunogenicity could be partially modulated by the sequence similarity to the host proteome. ELISpot responses to peptides spanning the entire viral proteome evaluated in 314 individuals showed a trend indicating an inverse relationship between the similarity to the host proteome and the frequency of recognition. In addition, analysis of responses by a group of 30 HIV-infected individuals against 944 overlapping peptides representing a broad range of individual HIV-1B Nef variants...

‣ Comparative Genomic Characterization of Francisella tularensis Strains Belonging to Low and High Virulence Subspecies

Champion, Mia D.; Zeng, Qiandong; Nix, Eli B.; Nano, Francis E.; Keim, Paul; Kodira, Chinnappa D.; Koehrsen, Michael; Pearson, Matthew; Howarth, Clint; Larson, Lisa; White, Jared; Alvarado, Lucia; Forsman, Mats; Bearden, Scott W.; Sjöstedt, Anders; Titba
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Tularemia is a geographically widespread, severely debilitating, and occasionally lethal disease in humans. It is caused by infection by a gram-negative bacterium, Francisella tularensis. In order to better understand its potency as an etiological agent as well as its potential as a biological weapon, we have completed draft assemblies and report the first complete genomic characterization of five strains belonging to the following different Francisella subspecies (subsp.): the F. tularensis subsp. tularensis FSC033, F. tularensis subsp. holarctica FSC257 and FSC022, and F. tularensis subsp. novicida GA99-3548 and GA99-3549 strains. Here, we report the sequencing of these strains and comparative genomic analysis with recently available public Francisella sequences, including the rare F. tularensis subsp. mediasiatica FSC147 strain isolate from the Central Asian Region. We report evidence for the occurrence of large-scale rearrangement events in strains of the holarctica subspecies, supporting previous proposals that further phylogenetic subdivisions of the Type B clade are likely. We also find a significant enrichment of disrupted or absent ORFs proximal to predicted breakpoints in the FSC022 strain, including a genetic component of the Type I restriction-modification defense system. Many of the pseudogenes identified are also disrupted in the closely related rarely human pathogenic F. tularensis subsp. mediasiatica FSC147 strain...

‣ Can You Sequence Ecology? Metagenomics of Adaptive Diversification

Marx, Christopher J
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Few areas of science have benefited more from the expansion in sequencing capability than the study of microbial communities. Can sequence data, besides providing hypotheses of the functions the members possess, detect the evolutionary and ecological processes that are occurring? For example, can we determine if a species is adapting to one niche, or if it is diversifying into multiple specialists that inhabit distinct niches? Fortunately, adaptation of populations in the laboratory can serve as a model to test our ability to make such inferences about evolution and ecology from sequencing. Even adaptation to a single niche can give rise to complex temporal dynamics due to the transient presence of multiple competing lineages. If there are multiple niches, this complexity is augmented by segmentation of the population into multiple specialists that can each continue to evolve within their own niche. For a known example of parallel diversification that occurred in the laboratory, sequencing data gave surprisingly few obvious, unambiguous signs of the ecological complexity present. Whereas experimental systems are open to direct experimentation to test hypotheses of selection or ecological interaction, the difficulty in “seeing ecology” from sequencing for even such a simple system suggests translation to communities like the human microbiome will be quite challenging. This will require both improved empirical methods to enhance the depth and time resolution for the relevant polymorphisms and novel statistical approaches to rigorously examine time-series data for signs of various evolutionary and ecological phenomena within and between species.; Organismic and Evolutionary Biology

‣ Evolution after Introduction of a Novel Metabolic Pathway Consistently Leads to Restoration of Wild-Type Physiology

Carroll, Sean; Marx, Christopher J
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Organisms cope with physiological stressors through acclimatizing mechanisms in the short-term and adaptive mechanisms over evolutionary timescales. During adaptation to an environmental or genetic perturbation, beneficial mutations can generate numerous physiological changes: some will be novel with respect to prior physiological states, while others might either restore acclimatizing responses to a wild-type state, reinforce them further, or leave them unchanged. We examined the interplay of acclimatizing and adaptive responses at the level of global gene expression in Methylobacterium extorquens AM1 engineered with a novel central metabolism. Replacing central metabolism with a distinct, foreign pathway resulted in much slower growth than wild-type. After 600 generations of adaptation, however, eight replicate populations founded from this engineered ancestor had improved up to 2.5-fold. A comparison of global gene expression in wild-type, engineered, and all eight evolved strains revealed that the vast majority of changes during physiological adaptation effectively restored acclimatizing processes to wild-type expression states. On average, 93% of expression perturbations from the engineered strain were restored, with 70% of these occurring in perfect parallel across all eight replicate populations. Novel changes were common but typically restricted to one or a few lineages...

‣ Historical Zoonoses and Other Changes in Host Tropism of Staphylococcus aureus, Identified by Phylogenetic Analysis of a Population Dataset

Shepheard, Marcus A.; Fleming, Vicki M.; Connor, Thomas R.; Corander, Jukka; Feil, Edward J.; Fraser, Christophe; Hanage, William P.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Background: Staphylococcus aureus exhibits tropisms to many distinct animal hosts. While spillover events can occur wherever there is an interface between host species, changes in host tropism only occur with the establishment of sustained transmission in the new host species, leading to clonal expansion. Although the genomic variation underpinning adaptation in S. aureus genotypes infecting bovids and poultry has been well characterized the frequency of switches from one host to another remains obscure. We sought to identify sustained switches in host tropism in the S. aureus population, both anthroponotic and zoonotic, and their distribution over the species phylogeny. Methodologies/Results We have used a sample of 3042 isolates, representing 696 distinct MLST genotypes, from a well-established database (www.mlst.net). Using an empirical parsimony approach (AdaptML) we have investigated the distribution of switches in host association between both human and non-human (henceforth referred to as animal) hosts. We reconstructed a credible description of past events in the form of a phylogenetic tree; the nodes and leaves of which are statistically associated with either human or animal habitats, estimated from extant host-association and the degree of sequence divergence between genotypes. We identified 15 likely historical switching events; 13 anthroponoses and two zoonoses. Importantly...

‣ Genomic Analysis of the Basal Lineage Fungus Rhizopus oryzae Reveals a Whole-Genome Duplication

Ma, Li-Jun; Ibrahim, Ashraf S.; Skory, Christopher; Grabherr, Manfred G.; Burger, Gertraud; Butler, Margi; Elias, Marek; Idnurm, Alexander; Lang, B. Franz; Sone, Teruo; Abe, Ayumi; Corrochano, Luis M.; Fu, Jianmin; Hansberg, Wilhelm; Kim, Jung-Mi; Kodira,
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Rhizopus oryzae is the primary cause of mucormycosis, an emerging, life-threatening infection characterized by rapid angioinvasive growth with an overall mortality rate that exceeds 50%. As a representative of the paraphyletic basal group of the fungal kingdom called “zygomycetes,” R. oryzae is also used as a model to study fungal evolution. Here we report the genome sequence of R. oryzae strain 99–880, isolated from a fatal case of mucormycosis. The highly repetitive 45.3 Mb genome assembly contains abundant transposable elements (TEs), comprising approximately 20% of the genome. We predicted 13,895 protein-coding genes not overlapping TEs, many of which are paralogous gene pairs. The order and genomic arrangement of the duplicated gene pairs and their common phylogenetic origin provide evidence for an ancestral whole-genome duplication (WGD) event. The WGD resulted in the duplication of nearly all subunits of the protein complexes associated with respiratory electron transport chains, the V-ATPase, and the ubiquitin–proteasome systems. The WGD, together with recent gene duplications, resulted in the expansion of multiple gene families related to cell growth and signal transduction, as well as secreted aspartic protease and subtilase protein families...

‣ Optimal Drug Synergy in Antimicrobial Treatments

Torella, Joseph; Chait, Remy Paul; Kishony, Roy
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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The rapid proliferation of antibiotic-resistant pathogens has spurred the use of drug combinations to maintain clinical efficacy and combat the evolution of resistance. Drug pairs can interact synergistically or antagonistically, yielding inhibitory effects larger or smaller than expected from the drugs' individual potencies. Clinical strategies often favor synergistic interactions because they maximize the rate at which the infection is cleared from an individual, but it is unclear how such interactions affect the evolution of multi-drug resistance. We used a mathematical model of in vivo infection dynamics to determine the optimal treatment strategy for preventing the evolution of multi-drug resistance. We found that synergy has two conflicting effects: it clears the infection faster and thereby decreases the time during which resistant mutants can arise, but increases the selective advantage of these mutants over wild-type cells. When competition for resources is weak, the former effect is dominant and greater synergy more effectively prevents multi-drug resistance. However, under conditions of strong resource competition, a tradeoff emerges in which greater synergy increases the rate of infection clearance, but also increases the risk of multi-drug resistance. This tradeoff breaks down at a critical level of drug interaction...

‣ Evidence-Based Annotation of the Malaria Parasite's Genome Using Comparative Expression Profiling

Zhou, Yingyao; Ramachandran, Vandana; Kumar, Kota Arun; Westenberger, Scott; Refour, Phillippe; Zhou, Bin; Li, Fengwu; Young, Jason A.; Chen, Kaisheng; Plouffe, David; Henson, Kerstin; Nussenzweig, Victor; Carlton, Jane; Vinetz, Joseph M.; Winzeler, Eliza
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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A fundamental problem in systems biology and whole genome sequence analysis is how to infer functions for the many uncharacterized proteins that are identified, whether they are conserved across organisms of different phyla or are phylum-specific. This problem is especially acute in pathogens, such as malaria parasites, where genetic and biochemical investigations are likely to be more difficult. Here we perform comparative expression analysis on Plasmodium parasite life cycle data derived from P. falciparum blood, sporozoite, zygote and ookinete stages, and P. yoelii mosquito oocyst and salivary gland sporozoites, blood and liver stages and show that type II fatty acid biosynthesis genes are upregulated in liver and insect stages relative to asexual blood stages. We also show that some universally uncharacterized genes with orthologs in Plasmodium species, Saccharomyces cerevisiae and humans show coordinated transcription patterns in large collections of human and yeast expression data and that the function of the uncharacterized genes can sometimes be predicted based on the expression patterns across these diverse organisms. We also use a comprehensive and unbiased literature mining method to predict which uncharacterized parasite-specific genes are likely to have roles in processes such as gliding motility...