Biology subjects

Kearney, S. M.

Publications and source records attributed to Kearney, S. M..

8 recordsLinked to original sources

bioRxiv2025

Influence of heterotrophs on phage infection of marine picocyanobacteria

Picocyanobacteria Prochlorococcus and Synechococcus coexist with both their lytic phages and heterotrophic bacteria in the oceans. These lytic phages are a significant cause of mortality, and heterotrophic bacteria have been shown to increase the fitness of Prochlorococcus by reducing oxidative stress and cross feeding under extended darkness. Studies of Prochlorococcus-phage interactions are often done with xenic cultures as it has been historically difficult to obtain and maintain heterotroph-free cultures. Here we examine the effects of heterotrophic bacteria on phage infection in Prochlorococcus and Synechococcus by comparing phage infection dynamics in cultures with and without heterotrophs present. We found that Prochlorococcus populations resumed growth following infection only in the presence of heterotrophs, independent of phage:host or heterotroph:host ratios. In phage:host pairing with Synechococcus the outcomes varied, suggesting that the impact of heterotrophs on phage infection may be dependent on the phage:host interaction. In cases where the host recovered from phage infection, heterotrophs appeared to facilitate it both by mitigating oxidative stress and possibly supplying organic carbon sources, which may support post-infection growth. Furthermore, Prochlorococcus and Synechococcus populations that recovered from infection were resistant to phage infection when transferred to fresh media. Evidence argues against genetic change as the mechanism of resistance, suggesting that Prochlorococcus and Synechococcus populations in co-culture with heterotrophs undergo non-genetic adaptations during recovery from phage infection, likely driven by heterotroph-derived organic compounds that reshape host metabolism and confer protection against future lysis.

microbiology↗

bioRxiv2023

Chitin degradation by Synechococcus WH7803

Chitin is an abundant, carbon-rich polymer in the marine environment. Chitinase activity has been detected in spent media of Synechococcus WH7803 cultures - yet it was unclear which specific enzymes were involved. Here we delivered a CRISPR tool into the cells via electroporation to generate loss-of-function mutants of putative candidates and identified ChiA as the enzyme required for the activity detected in the wild type.

microbiology↗

bioRxiv2020

Microbial Diversity of Co-occurring Heterotrophs in Cultures of Marine Picocyanobacteria

Prochlorococcus and Synechococcus are responsible for around 10% of global net primary productivity, serving as part of the foundation of marine food webs. Heterotrophic bacteria are often co-isolated with these picocyanobacteria in seawater enrichment cultures that contain no added organic carbon; heterotrophs grow on organic carbon supplied by the photolithoautotrophs. We have maintained these cultures of Prochlorococcus and Synechococcus for 100s to 1000s of generations; they represent ideal microcosms for examining the selective pressures shaping autotroph/heterotroph interactions. Here we examine the diversity of heterotrophs in 74 enrichment cultures of these picocyanobacteria obtained from diverse areas of the global oceans. Heterotroph community composition differed between clades and ecotypes of the autotrophic hosts but there was significant overlap in heterotroph community composition. Differences were associated with timing, location, depth, and methods of isolation, suggesting the particular conditions surrounding isolation have a persistent effect on long-term culture composition. The majority of heterotrophs in the cultures are rare in the global ocean; enrichment conditions favor the opportunistic outgrowth of these rare bacteria. We did find a few examples, such as heterotrophs in the family Rhodobacteraceae, that are ubiquitous and abundant in cultures and in the global oceans; their abundance in the wild is also positively correlated with that of picocyanobacteria. Collectively, the cultures converged on similar compositions, likely from bottlenecking and selection that happens during the early stages of enrichment for the picocyanobacteria. We highlight the potential for examining ecologically relevant relationships by identifying patterns of distribution of culture-enriched organisms in the global oceans. IMPORTANCEOne of the biggest challenges in marine microbial ecology is to begin to understand the rules that govern the self-assembly of these complex communities. The picocyanobacteria Prochlorococcus and Synechococcus comprise the most numerous photosynthetic organisms in the sea and supply a significant fraction of the organic carbon that feeds diverse heterotrophic microbes. When initially isolated into cultures, Prochlorococcus and Synechococcus carry with them select heterotrophic microorganisms that depend on them for organic carbon. The cultures self-assemble into stable communities of diverse microorganisms and are microcosms for understanding microbial interdependencies. Primarily faster-growing, relatively rare, copiotrophic heterotrophic bacteria - as opposed to oligotrophic bacteria that are abundant in picocyanobacterial habitats - are selected for in these cultures, suggesting that these copiotrophs experience these cultures as they would high carbon fluxes associated with particles, phycospheres of larger cells, or actual attachment to picocyanobacteria in the wild.

microbiology↗

bioRxiv2020

Industrialization is associated with elevated rates of horizontal gene transfer in the human microbiome

Horizontal Gene Transfer, the process by which bacteria acquire new genes and functions from non-parental sources, is common in the human microbiome 1,2. If the timescale of HGT is rapid compared to the timescale of human colonization, then it could have the effect of personalizing bacterial genomes by providing incoming strains with the genes necessary to adapt to the diet or lifestyle of a new host. The extent to which HGT occurs on the timescale of human colonization, however, remains unclear. Here, we analyzed 6,188 newly isolated and sequenced gut bacteria from 34 individuals in 9 human populations, and show that HGT is more common among bacteria isolated from the same human host, indicating that the timescale of transfer is short compared to the timescale of human colonization. Comparing across 9 human populations reveals that high rates of transfer may be a recent development in human history linked to industrialization and urbanization. In addition, we find that the genes involved in transfer reflect the lifestyle of the human hosts, with elevated transfer of carbohydrate metabolism genes in hunter gatherer populations, and transfer of antibiotic resistance genes among pastoralists who live in close contact with livestock. These results suggest that host-associated bacterial genomes are not static within individuals, but continuously acquire new functionality based on host diet and lifestyle.

microbiology↗

bioRxiv2019

24-hour multi-omics analysis of residential sewage reflects human activity and informs public health

High-throughput molecular analysis of sewage is a promising tool for precision public health. Here, we combine sewer network and demographic data to identify a residential catchment for sampling, and explore the potential of applying untargeted genomics and metabolomics to sewage to collect actionable public health data. We find that wastewater sampled upstream in a residential catchment is representative of the human microbiome and metabolome, and we are able to identify glucuronidated compounds indicative of direct human excretion, which are typically degraded too quickly to be detected at treatment plants. We show that diurnal variations during 24-hour sampling can be leveraged to discriminate between biomarkers in sewage that are associated with human activity from those related to the environmental background. Finally, we putatively annotate a suite of human-associated metabolites, including pharmaceuticals, food metabolites, and biomarkers of human health and activity, suggesting that mining untargeted data derived from residential sewage can expand currently-used biomarkers with direct public health or policy relevance.

genomics↗

bioRxiv2019

Dynamic colonization of microbes and their functions after fecal microbiota transplantation for inflammatory bowel disease

For fecal microbiota transplantation (FMT) to be successful in complex immune diseases like inflammatory bowel disease (IBD), it is assumed that therapeutic microbes and their beneficial functions and immune interactions must colonize the recipient and persist in sufficient quantity and for a long enough period of time to result in a clinical benefit. But few studies have comprehensively profiled the colonization and persistence of transferred microbes along with the transfer of their microbial and immune functions. Using 16S, metagenomic, and immunoglobulin A (IgA) sequencing, we analyzed hundreds of longitudinal microbiome samples from a randomized controlled trial of 12 patients with ulcerative colitis who received fecal transplant or placebo for 12 weeks. We uncovered a range of competitive dynamics among donor and patient strains, showing that persistence of transferred microbes is far from static. Indeed, one patient experienced dramatic loss of donor bacteria 10 weeks into the trial, coinciding with a bloom of pathogenic bacteria and worsening clinical symptoms. We similarly evaluated transfer of microbial functions, including desired ones like butyrate production and unintended ones like antibiotic resistance. By profiling bacteria coated with IgA, we identified IgA-coated bacteria associated with inflammation, and we found that microbial interactions with the host immune system can be transferred across people. This transfer of immune function is likely critical for gut microbiome therapeutics for immune-related diseases. Our findings elucidate the colonization dynamics of gut microbes as well as their functions in the context of FMT to treat a complex disease--information that may provide a critical foundation for the development of more-targeted therapeutics.

microbiology↗

bioRxiv2019

Non-responder phenotype reveals microbiome-wide antibiotic resistance in the murine gut

Broad spectrum antibiotics can cause both transient and lasting damage to the ecology of the gut microbiome. Loss of gut bacterial diversity has been linked to immune dysregulation and disease susceptibility. Antibiotic-resistant populations of cells are known to arise spontaneously in single-strain systems. Furthermore, prior work on subtherapeutic antibiotic treatment in humans and therapeutic treatments in non-human animals have suggested that entire gut communities may exhibit spontaneous resistance phenotypes. In this study, we validate the existence of these community resistance phenotypes in the murine gut and explore how antibiotic duration or diet influence the frequency of this phenotype. We find that almost a third of mice exhibit whole-community resistance to a therapeutic concentration of the {beta}-lactam antibiotic cefoperazone, independent of antibiotic treatment duration or xenobiotic dietary amendment. These non-responder (i.e. resistant) microbiota were protected from biomass depletion, transient ecological community collapse, and lasting diversity loss seen in the susceptible microbiota. There were no major differences between non-responder microbiota and untreated control microbiota at the community structure level. However, gene expression was vastly different between non-responder microbiota and controls during antibiotic treatment, with non-responder communities showing an upregulation of antimicrobial resistance genes and a down-regulation of central metabolism. Thus, non-responder phenotypes appear to combat antibiotic assault through a combination of efflux transporter upregulation and a reduced growth rate across the entire gut community. Future work should focus on what factors are responsible for tipping entire communities from susceptible to resistant phenotypes so that we might harness this phenomenon to protect our microbiota from exposure to therapeutic antibiotic treatment regimes.

systems biology↗

bioRxiv2017

Endospores and other lysis-resistant bacteria comprise a widely shared core community within the human microbiota

Endospore-formers in the human microbiota are well adapted for host-to-host transmission, and an emerging consensus points to their role in determining health and disease states in the gut. The human gut, more than any other environment, encourages the maintenance of endospore formation, with recent culture-based work suggesting that over 50% of genera in the microbiome carry genes attributed to this trait. However, there has been limited work on the ecological role of endospores and other stress-resistant cellular states in the human gut. In fact, there is no data to indicate whether organisms with the genetic potential to form endospores actually form endospores in situ and how sporulation varies across individuals and over time. Here, we applied a culture-independent protocol to enrich for endospores and other stress-resistant cells in human feces to identify variation in these states across people and within an individual over time. We see that cells with resistant states are more likely than those without to be shared among multiple individuals, which suggests that these resistant states are particularly adapted for cross-host dissemination. Furthermore, we use untargeted fecal metabolomics in 24 individuals and within a person over time to show that these organisms respond to shared environmental signals, and in particular, dietary fatty acids, that likely mediate colonization of recently disturbed human guts.

microbiology↗