Publications by authors named "Alexander B Chase"

13 Publications

  • Page 1 of 1

Adaptive differentiation and rapid evolution of a soil bacterium along a climate gradient.

Proc Natl Acad Sci U S A 2021 May;118(18)

Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92697.

Microbial community responses to environmental change are largely associated with ecological processes; however, the potential for microbes to rapidly evolve and adapt remains relatively unexplored in natural environments. To assess how ecological and evolutionary processes simultaneously alter the genetic diversity of a microbiome, we conducted two concurrent experiments in the leaf litter layer of soil over 18 mo across a climate gradient in Southern California. In the first experiment, we reciprocally transplanted microbial communities from five sites to test whether ecological shifts in ecotypes of the abundant bacterium, , corresponded to past adaptive differentiation. In the transplanted communities, ecotypes converged toward that of the native communities growing on a common litter substrate. Moreover, these shifts were correlated with community-weighted mean trait values of the ecotypes, indicating that some of the trait variation among ecotypes could be explained by local adaptation to climate conditions. In the second experiment, we transplanted an isogenic strain and tracked genomic mutations associated with the sites across the same climate gradient. Using a combination of genomic and metagenomic approaches, we identified a variety of nonrandom, parallel mutations associated with transplantation, including mutations in genes related to nutrient acquisition, stress response, and exopolysaccharide production. Together, the field experiments demonstrate how both demographic shifts of previously adapted ecotypes and contemporary evolution can alter the diversity of a soil microbiome on the same timescale.
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http://dx.doi.org/10.1073/pnas.2101254118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106337PMC
May 2021

Grincamycins P-T: Rearranged Angucyclines from the Marine Sediment-Derived sp. CNZ-748 Inhibit Cell Lines of the Rare Cancer Pseudomyxoma Peritonei.

J Nat Prod 2021 05 26;84(5):1638-1648. Epub 2021 Apr 26.

Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, United States.

While marine natural products have been investigated for anticancer drug discovery, they are barely screened against rare cancers. Thus, in our effort to discover potential drug leads against the rare cancer pseudomyxoma peritonei (PMP), which currently lacks effective drug treatments, we screened extracts of marine actinomycete bacteria against the PMP cell line ABX023-1. This effort led to the isolation of nine rearranged angucyclines from sp. CNZ-748, including five new analogues, namely, grincamycins P-T (-). The chemical structures of these compounds were unambiguously established based on spectroscopic and chemical analyses. Particularly, grincamycin R () possesses an -containing α-l-methylthio-aculose residue, which was discovered in nature for the first time. All of the isolated compounds were evaluated against four PMP cell lines and some exhibited low micromolar inhibitory activities. To identify a candidate biosynthetic gene cluster (BGC) encoding the grincamycins, we sequenced the genome of the producing strain, sp. CNZ-748, and compared the BGCs detected with those linked to the production of angucyclines with different aglycon structures.
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http://dx.doi.org/10.1021/acs.jnatprod.1c00179DOI Listing
May 2021

High-Fiber, Whole-Food Dietary Intervention Alters the Human Gut Microbiome but Not Fecal Short-Chain Fatty Acids.

mSystems 2021 Mar 16;6(2). Epub 2021 Mar 16.

Department of Molecular Biology and Biochemistry, University of California, Irvine, California, USA

Dietary shifts can have a direct impact on the gut microbiome by preferentially selecting for microbes capable of utilizing the various dietary nutrients. The intake of dietary fiber has decreased precipitously in the last century, while consumption of processed foods has increased. Fiber, or microbiota-accessible carbohydrates (MACs), persist in the digestive tract and can be metabolized by specific bacteria encoding fiber-degrading enzymes. The digestion of MACs results in the accumulation of short-chain fatty acids (SCFAs) and other metabolic by-products that are critical to human health. Here, we implemented a 2-week dietary fiber intervention aiming for 40 to 50 g of fiber per day within the context of a course-based undergraduate research experience (CURE) ( = 20). By coupling shotgun metagenomic sequencing and targeted gas chromatography-mass spectrometry (GC-MS), we found that the dietary intervention significantly altered the composition of individual gut microbiomes, accounting for 8.3% of the longitudinal variability within subjects. Notably, microbial taxa that increased in relative abundance as a result of the diet change included known MAC degraders (i.e., and ). We further assessed the genetic diversity within , assayed by amplification of the gene. Concomitant with microbial composition changes, we show an increase in the abundance of genes involved in inositol degradation. Despite these changes in gut microbiome composition, we did not detect a consistent shift in SCFA abundance. Collectively, our results demonstrate that on a short-term timescale of 2 weeks, increased fiber intake can induce compositional changes of the gut microbiome, including an increase in MAC-degrading bacteria. A profound decrease in the consumption of dietary fiber in many parts of the world in the last century may be associated with the increasing prevalence of type II diabetes, colon cancer, and other health problems. A typical U.S. diet includes about ∼15 g of fiber per day, far less fiber than the daily recommended allowance. Changes in dietary fiber intake affect human health not only through the uptake of nutrients directly but also indirectly through changes in the microbial community and their associated metabolism. Here, we conducted a 2-week diet intervention in healthy young adults to investigate the impact of fiber consumption on the gut microbiome. Participants increased their average fiber consumption by 25 g/day on average for 2 weeks. The high-fiber diet intervention altered the gut microbiome of the study participants, including increases in known fiber-degrading microbes, such as and .
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http://dx.doi.org/10.1128/mSystems.00115-21DOI Listing
March 2021

Six novel species of the obligate marine actinobacterium , sp. nov., sp. nov., sp. nov., sp. nov., sp. nov. and sp. nov., and emended description of the genus .

Int J Syst Evol Microbiol 2020 Aug 23;70(8):4668-4682. Epub 2020 Jul 23.

Departamento de Microbiología y Genética, Campus Miguel de Unamuno, Universidad de Salamanca, 37007 Salamanca, Spain.

Ten representative actinobacterial strains isolated from marine sediments collected worldwide were studied to determine their taxonomic status. The strains were previously identified as members of the genus and shared >99 % 16S rRNA gene sequence similarity to the three currently recognized species. Comparative genomic analyses resulted in the delineation of six new species based on average nucleotide identity and digital DNA-DNA hybridization values below 95 and 70 %, respectively. The species status of the six new groups was supported by a core-genome phylogeny reconstructed from 2106 orthologs detected in 118 publicly available genomes. Chemotaxonomic and physiological studies were used to complete the phenotypic characterization of the strains. The fatty acid profiles contained the major components iso-C, C, iso- and anteiso C. Galactose and xylose were common in all whole-sugar patterns but differences were found between the six groups of strains. Polar lipid compositions were also unique for each species. Distinguishable physiological and biochemical characteristics were also recorded. The names proposed are sp. nov., CNY-202 (=DSM 108615=CECT 9739); sp. nov., CNT-569 (=DSM 108614=CECT 9740); sp. nov., CNY-666 (=DSM 108616=CECT 9738); sp. nov., CNT-150 (=DSM 45549=CECT 9741); sp. nov., CNT-138 (=DSM 45547=CECT 9742); and sp. nov., CNT-148 (=DSM 45548=CECT 9743).
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http://dx.doi.org/10.1099/ijsem.0.004330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660244PMC
August 2020

Fiber Force: A Fiber Diet Intervention in an Advanced Course-Based Undergraduate Research Experience (CURE) Course.

J Microbiol Biol Educ 2020 30;21(1). Epub 2020 Apr 30.

Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697.

Course-based undergraduate research experiences (CUREs) are an effective way to introduce students to contemporary scientific research. Research experiences have been shown to promote critical thinking, improve understanding and proper use of the scientific method, and help students learn practical skills including writing and oral communication. We aimed to improve scientific training by engaging students enrolled in an upper division elective course in a human microbiome CURE. The "Fiber Force" course is aimed at studying the effect of a wholesome high-fiber diet (40 to 50 g/day for two weeks) on the students' gut microbiomes. Enrolled students participated in a noninvasive diet intervention, designed health surveys, tested hypotheses on the effect of a diet intervention on the gut microbiome, and analyzed their own samples (as anonymized aggregates). The course involved learning laboratory techniques (e.g., DNA extraction, PCR, and 16S sequencing) and the incorporation of computational techniques to analyze microbiome data with QIIME2 and within the R software environment. In addition, the learning objectives focused on effective student performance in writing, data analysis, and oral communication. Enrolled students showed high performance grades on writing, data analysis and oral communication assignments. Pre- and post-course surveys indicate that the students found the experience favorable, increased their interest in science, and heightened awareness of their diet habits. Fiber Force constitutes a validated case of a research experience on microbiology with the capacity to improve research training and promote healthy dietary habits.
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http://dx.doi.org/10.1128/jmbe.v21i1.1991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198227PMC
April 2020

Maintenance of Sympatric and Allopatric Populations in Free-Living Terrestrial Bacteria.

mBio 2019 10 29;10(5). Epub 2019 Oct 29.

Department of Ecology and Evolutionary Biology, University of California, Irvine, California, USA.

For free-living bacteria and archaea, the equivalent of the biological species concept does not exist, creating several obstacles to the study of the processes contributing to microbial diversification. These obstacles are particularly high in soil, where high bacterial diversity inhibits the study of closely related genotypes and therefore the factors structuring microbial populations. Here, we isolated strains within a single ecotype from surface soil (leaf litter) across a regional climate gradient and investigated the phylogenetic structure, recombination, and flexible gene content of this genomic diversity to infer patterns of gene flow. Our results indicate that microbial populations are delineated by gene flow discontinuities, with distinct populations cooccurring at multiple sites. Bacterial population structure was further delineated by genomic features allowing for the identification of candidate genes possibly contributing to local adaptation. These results suggest that the genetic structure within this bacterium is maintained both by ecological specialization in localized microenvironments (isolation by environment) and by dispersal limitation between geographic locations (isolation by distance). Due to the promiscuous exchange of genetic material and asexual reproduction, delineating microbial species (and, by extension, populations) remains challenging. Because of this, the vast majority of microbial studies assessing population structure often compare divergent strains from disparate environments under varied selective pressures. Here, we investigated the population structure within a single bacterial ecotype, a unit equivalent to a eukaryotic species, defined as highly clustered genotypic and phenotypic strains with the same ecological niche. Using a combination of genomic and computational analyses, we assessed the phylogenetic structure, extent of recombination, and flexible gene content of this genomic diversity to infer patterns of gene flow. To our knowledge, this study is the first to do so for a dominant soil bacterium. Our results indicate that bacterial soil populations, similarly to those in other environments, are structured by gene flow discontinuities and exhibit distributional patterns consistent with both isolation by distance and isolation by environment. Thus, both dispersal limitation and local environments contribute to the divergence among closely related soil bacteria as observed in macroorganisms.
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http://dx.doi.org/10.1128/mBio.02361-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819660PMC
October 2019

Experimental Evidence that Stochasticity Contributes to Bacterial Composition and Functioning in a Decomposer Community.

mBio 2019 04 16;10(2). Epub 2019 Apr 16.

Dept. of Ecology and Evolutionary Biology, University of California, Irvine, Irvine, California, USA

Stochasticity emerging from random differences in replication, death, mutation, and dispersal is thought to alter the composition of ecological communities. However, the importance of stochastic effects remains somewhat speculative because stochasticity is not directly measured but is instead inferred from unexplained variations in beta-diversity. Here, we performed a field experiment to more directly disentangle the role of stochastic processes, environmental selection, and dispersal in the composition and functioning of a natural bacterial decomposer community in the field. To increase our ability to detect these effects, we reduced initial biological and environmental heterogeneity using replicate nylon litterbags in the field. We then applied two treatments: ambient/added precipitation and bacterial and fungal dispersal using "open" litterbags (made from 18.0-μm-pore-size mesh) ("open bacterial dispersal") versus bacterial and fungal dispersal using "closed" litterbags (made from 22.0-μm-pore-size mesh) ("closed bacterial dispersal"). After 5 months, we assayed composition and functioning by the use of three subsamples from each litterbag to disentangle stochastic effects from residual variation. Our results indicate that stochasticity via ecological drift can contribute to beta-diversity in bacterial communities. However, residual variation, which had previously been included in stochasticity estimates, accounted for more than four times as much variability. At the same time, stochastic effects on beta-diversity were not attenuated at the functional level, as measured by genetic functional potential and extracellular enzyme activity. Finally, dispersal was found to interact with precipitation availability to influence the degree to which stochasticity contributed to functional variation. Together, our results demonstrate that the ability to quantify stochastic processes is key to understanding microbial diversity and its role in ecosystem functioning. Randomness can alter the diversity and composition of ecological communities. Such stochasticity may therefore obscure the relationship between the environment and community composition and hinder our ability to predict the relationship between biodiversity and ecosystem functioning. This study investigated the role of stochastic processes, environmental selection, and dispersal in microbial composition and its functioning on an intact field community. To do this, we used a controlled and replicated experiment that was similar to that used to study population genetics in the laboratory. Our study showed that, while the stochastic effects on taxonomic composition are smaller than expected, the degree to which stochasticity contributes to variability in ecosystem processes may be much higher than previously assumed.
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http://dx.doi.org/10.1128/mBio.00568-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469972PMC
April 2019

Cystic Fibrosis-Associated Stenotrophomonas maltophilia Strain-Specific Adaptations and Responses to pH.

J Bacteriol 2019 04 13;201(7). Epub 2019 Mar 13.

Department of Molecular Biology and Biochemistry, University of California, Irvine, California, USA

The airway fluids of cystic fibrosis (CF) patients contain local pH gradients and are more acidic than those of healthy individuals. pH is a critical factor that is often overlooked in studies seeking to recapitulate the infection microenvironment. We sought to determine the impact of pH on the physiology of a ubiqituous yet understudied microbe, Phylogenomics was first used to reconstruct evolutionary relationships between 74 strains of (59 from CF patients). Neither the core genome (2,158 genes) nor the accessory genome (11,978 genes) distinguish the CF and non-CF isolates; however, strains from similar isolation sources grouped into the same subclades. We grew two human and six CF isolates from different subclades at a range of pH values and observed impaired growth and altered antibiotic tolerances at pH 5. Transcriptomes revealed increased expression of both antibiotic resistance and DNA repair genes in acidic conditions. Although the gene expression profiles of in lab cultures and CF sputum were distinct, we found that the same genes associated with low pH were also expressed during infection, and the higher pH cultures were more similar to sputum metatranscriptomes. Our findings suggest that is not well adapted to acidity and may cope with low pH by expressing stress response genes and colonizing less acidic microenvironments. As a whole, our study underlines the impact of microenvironments on bacterial colonization and adaptation in CF infections. Understanding bacterial responses to physiological conditions is an important priority for combating opportunistic infections. The majority of CF patients succumb to inflammation and necrosis in the airways, arising from chronic infection due to ineffective mucociliary clearance. Steep pH gradients characterize the CF airways but are not often incorporated in standard microbiology culture conditions. is a prevalent CF opportunistic pathogen also found in many disparate environments, yet this bacterium's contribution to CF lung damage and its response to changing environmental factors remain largely understudied. Here, we show that pH impacts the physiology and antibiotic susceptibility of , with implications for the development of relevant models and assessment of antibiotic sensitivity.
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http://dx.doi.org/10.1128/JB.00478-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416904PMC
April 2019

Emergence of soil bacterial ecotypes along a climate gradient.

Environ Microbiol 2018 11 5;20(11):4112-4126. Epub 2018 Oct 5.

Department of Ecology and Evolutionary Biology, University of California, Irvine, California, USA.

The high diversity of soil bacteria is attributed to the spatial complexity of soil systems, where habitat heterogeneity promotes niche partitioning among bacterial taxa. This premise remains challenging to test, however, as it requires quantifying the traits of closely related soil bacteria and relating these traits to bacterial abundances and geographic distributions. Here, we sought to investigate whether the widespread soil taxon Curtobacterium consists of multiple coexisting ecotypes with differential geographic distributions. We isolated Curtobacterium strains from six sites along a climate gradient and assayed four functional traits that may contribute to niche partitioning in leaf litter, the top layer of soil. Our results revealed that cultured isolates separated into fine-scale genetic clusters that reflected distinct suites of phenotypic traits, denoting the existence of multiple ecotypes. We then quantified the distribution of Curtobacterium by analysing metagenomic data collected across the gradient over 18 months. Six abundant ecotypes were observed with differential abundances along the gradient, suggesting fine-scale niche partitioning. However, we could not clearly explain observed geographic distributions of ecotypes by relating their traits to environmental variables. Thus, while we can resolve soil bacterial ecotypes, the traits delineating their distinct niches in the environment remain unclear.
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http://dx.doi.org/10.1111/1462-2920.14405DOI Listing
November 2018

Microdiversity of an Abundant Terrestrial Bacterium Encompasses Extensive Variation in Ecologically Relevant Traits.

mBio 2017 11 14;8(6). Epub 2017 Nov 14.

Department of Ecology and Evolutionary Biology, University of California, Irvine, California, USA.

Much genetic diversity within a bacterial community is likely obscured by microdiversity within operational taxonomic units (OTUs) defined by 16S rRNA gene sequences. However, it is unclear how variation within this microdiversity influences ecologically relevant traits. Here, we employ a multifaceted approach to investigate microdiversity within the dominant leaf litter bacterium, , which comprises 7.8% of the bacterial community at a grassland site undergoing global change manipulations. We use cultured bacterial isolates to interpret metagenomic data, collected over 2 years, together with lab-based physiological assays to determine the extent of trait variation within this abundant OTU. The response of to seasonal variability and the global change manipulations, specifically an increase in relative abundance under decreased water availability, appeared to be conserved across six lineages identified at this site. Genomic and physiological analyses in the lab revealed that degradation of abundant polymeric carbohydrates within leaf litter, cellulose and xylan, is nearly universal across the genus, which may contribute to its high abundance in grassland leaf litter. However, the degree of carbohydrate utilization and temperature preference for this degradation varied greatly among clades. Overall, we find that traits within are conserved at different phylogenetic depths. We speculate that similar to bacteria in marine systems, diverse microbes within this taxon may be structured in distinct ecotypes that are key to understanding abundance and distribution in the environment. Despite the plummeting costs of sequencing, characterizing the fine-scale genetic diversity of a microbial community-and interpreting its functional importance-remains a challenge. Indeed, most studies, particularly studies of soil, assess community composition at a broad genetic level by classifying diversity into taxa (OTUs) defined by 16S rRNA sequence similarity. However, these classifications potentially obscure variation in traits that result in fine-scale ecological differentiation among closely related strains. Here, we investigated "microdiversity" in a highly diverse and poorly characterized soil system (leaf litter in a southern Californian grassland). We focused on the most abundant bacterium, , which by standard methods is grouped into only one OTU. We find that the degree of carbohydrate usage and temperature preference vary within the OTU, whereas its responses to changes in precipitation are relatively uniform. These results suggest that microdiversity may be key to understanding how soil bacterial diversity is linked to ecosystem functioning.
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http://dx.doi.org/10.1128/mBio.01809-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686540PMC
November 2017

Evidence for Ecological Flexibility in the Cosmopolitan Genus .

Front Microbiol 2016 22;7:1874. Epub 2016 Nov 22.

Department of Ecology and Evolutionary Biology, University of California, Irvine Irvine, CA, USA.

Assigning ecological roles to bacterial taxa remains imperative to understanding how microbial communities will respond to changing environmental conditions. Here we analyze the genus , as it was found to be the most abundant taxon in a leaf litter community in southern California. Traditional characterization of this taxon predominantly associates it as the causal pathogen in the agricultural crops of dry beans. Therefore, we sought to investigate whether the abundance of this genus was because of its role as a plant pathogen or another ecological role. By collating >24,000 16S rRNA sequences with 120 genomes across the Microbacteriaceae family, we show that has a global distribution with a predominant presence in soil ecosystems. Moreover, this genus harbors a high diversity of genomic potential for the degradation of carbohydrates, specifically with regards to structural polysaccharides. We conclude that may be responsible for the degradation of organic matter within litter communities.
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http://dx.doi.org/10.3389/fmicb.2016.01874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118839PMC
November 2016