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At least 109 records · Page 6

A novel bivalent chromatin associates with rapid induction of camalexin biosynthesis genes in response to a pathogen signal in Arabidopsis

Temporal dynamics of gene expression underpin responses to internal and environmental stimuli. In eukaryotes, regulation of gene induction includes changing chromatin states at target genes and recruiting the transcriptional machinery that includes transcription factors. As one of the most potent defense compounds in Arabidopsis thaliana , camalexin can be rapidly induced by bacterial and fungal infections. Though several transcription factors controlling camalexin biosynthesis genes have been characterized, how the rapid activation of genes in this pathway upon a pathogen signal is enabled remains unknown. By combining publicly available epigenomic data with in vivo chromatin modification mapping, we found that camalexin biosynthesis genes are marked with two epigenetic modifications with opposite effects on gene expression, trimethylation of lysine 27 of histone 3 (H3K27me3) (repression) and acetylation of lysine 18 of histone 3 (H3K18ac) (activation), to form a previously uncharacterized type of bivalent chromatin. Mutants with reduced H3K27me3 or H3K18ac suggested that both modifications were required to determine the timing of gene expression and metabolite accumulation at an early stage of the stress response. Our study indicates that the H3K27me3-H3K18ac bivalent chromatin, which we name as kairostat, plays an important role in controlling the timely induction of gene expression upon stress stimuli in plants.

59 BASIC BIOLOGICAL SCIENCES↗

Development and testing of a mouse simulated space flight model

The development and testing of a mouse model for simulating some aspects of weightlessness that occur during space flight, and the carrying out of immunological flight experiments on animals was discussed. The mouse model is an antiorthostatic, hypokinetic, hypodynamic suspension model similar to the one used with rats. It is shown that this murine model yield similar results to the rat model of antiorthostatic suspension for simulating some aspects of weightlessness. It is also shown that mice suspended in this model have decreased interferon-alpha/beta production as compared to control, nonsuspended mice or to orthostatically suspended mice. It is suggested that the conditions occuring during space flight could possibly affect interferon production. The regulatory role of interferon in nonviral diseases is demonstrated including several bacterial and protozoan infections indicating the great significance of interferon in resistance to many types of infectious diseases.

Sonnenfeld, G.↗

Effects of microgravity on the immune system

Changes in resistance to bacterial and viral infections in Apollo crew members has stimulated interest in the study of immunity and space flight. Results of studies from several laboratories in both humans and rodents have indicated alterations after space flight that include the following immunological parameters: thymus size, lymphocyte blastogenesis, interferon and interleukin production, natural killer cell activity, cytotoxic T-cell activity, leukocyte subset population distribution, response of bone marrow cells to colony stimulating factors, and delayed hypersensitivity skin test reactivity. The interactions of the immune system with other physiological systems, including muscle, bone, and the nervous system, may play a major role in the development of these immunological parameters during and after flight. There may also be direct effects of space flight on immune responses.

Sonnenfeld, Gerald↗

Microbial Adaptation to Spaceflight Is Correlated With Bacteriophage-Encoded Functions

Evidence from the International Space Station suggests microbial populations are rapidly adapting to the spacecraft environment; however, the mechanism of this adaptation is not understood. Bacteriophages are prolific mediators of bacterial adaptation on Earth. Here we survey 245 genomes sequenced from bacterial strains isolated on the International Space Station for dormant (lysogenic) bacteriophages. Our analysis indicates phage-associated genes are significantly different between spaceflight strains and their terrestrial counterparts. Additionally, we identify 283 complete prophages, those that could initiate bacterial lysis and infect additional hosts, of which 21% are novel. These prophage regions encode functions that correlate with increased persistence in extreme environments, such as spaceflight, to include antimicrobial resistance and virulence, DNA damage repair, and dormancy. Our results correlate microbial adaptation in spaceflight to bacteriophage-encoded functions that may impact human health in spaceflight.

Space Biology↗

ISS Technology Demonstrations for Future Spaceflight Medical Systems

Throughout the history of human spaceflight, crewmembers have experienced various in-flight medical conditions including illness and injury. Planned missions to the Moon and Mars will require capabilities to maintain the health of future space travelers. Mass, power, and volume available in the vehicles and habitats for these missions will be severely constrained; resupply of resources will be limited or non-existent, as will opportunities for evacuation to Earth. Furthermore, ground-based support will be hampered by communication latencies and blackouts. These vehicle and mission constraints will necessitate a medical system that has been efficiently planned, providing on-board procedural guidance in addition to a variety of medical devices and consumable resources. Medical capabilities required for the diagnosis and treatment of potential medical conditions during future spaceflight missions may include real-time health monitoring, medical imaging, and biomarker analyses ( e.g., blood or urine). Terrestrial medicine shares these needs, thus many of these medical capabilities could likely be satisfied by Commercial-Off-The-Shelf (COTS) devices and methodologies; however, in some cases the unique space environment and increased mission duration will drive the need to modify technologies and the way care is provided. NASA’s Human Research Program (HRP) Exploration Medical Capability (ExMC) Element and Mars Campaign Office’s Exploration Medical Integrated Product Team (XMIPT) are working together to decrease medical risk during exploration missions. Flight-tested medical diagnostic and treatment technologies are necessary to effectively manage medical conditions relevant to exploration missions while meeting vehicle constraints, integrating with medical decision-support tools, and enabling increasingly Earth-independent operations. Several projects have leveraged the ISS as a testbed for exploration, including 1) i n- situ blood analysis, 2) medical inventory, 3) intravenous fluid generation, and 4) autonomous medical procedure guidance. Management of several in-flight medical conditions, such as bacterial and viral infections and acute radiation syndrome, is dramatically improved with ability to assess blood cell populations, electrolytes, and metabolites. I n December 2020 and January 2021 ExMC performed an ISS technology demonstration (Tech Demo) of the HemoCue® WBC DIFF analyzer (HemoCue, Brea, CA), a COTS device that was modified to enable functionality in a spaceflight environment. This Tech Demo marked the first time that hematology measurements were successfully performed real-time in microgravity. Also modified and demonstrated was the reusable Handheld Electrolytes and Lab Technology for Humans (rHEALTH) ONE analyzer (rHEALTH, Bedford, MA), which uses flow cytometry and sheath-based hydrodynamic focusing methodologies. The rHEALTH ONE ISS Tech Demo in May 2022 demonstrated test results obtained in-flight matched those on the ground. NASA currently relies on crew self-reporting to manage and maintain medical inventory on ISS.The ability to maintain an accurate inventory becomes more critical during long duration missions since the crew will need to be increasingly autonomous in finding and utilizing medical items, including those scenarios when alternative treatments need to be considered due to limited or no resupply. HRP’s Medical Consumables Tracking (MCT) project was developed by ZIN Technologies, Inc. (Cleveland, OH), and demonstrated real-time tracking of medical supplies aboard the ISS between December 2016 and July 2018. The MCT system design utilized Radio Frequency Identification Device (RFID) technology to perform automated inventory and was installed in the Crew Health Care System (CHeCS) Resupply Stowage Rack (RSR). The challenge of limited shelf life, exacerbated by the lack of resupply opportunities, affects a plethora of medical system components including consumables, pharmaceuticals, and intravenous (IV) fluid. In 2010, ExMC funded ZIN Technologies, Inc. (Cleveland, OH), to develop the Intravenous Fluid Generation (IVGEN) system. IV fluids were successfully generated with IVGEN using the potable water supply on ISS during ISS Expedition 23. The XMIPT is in the process of developing a miniaturized version of the original IVGEN hardware for a future Tech Demo aboard the ISS. Current ISS medical operations rely heavily on preflight training and real-time remote guidance, both of which become impractical or impossible for exploration missions. The primary goal of the Autonomous Medical Officer Support (AMOS) Software Tech Demos on ISS was to confirm telemedical proof-of-concept for autonomous medical imaging in an operational setting. This novel software tool shifts emphasis from preflight training and real-time remote guidance to in-flight just-in-time instruction, a new and necessary paradigm for crew medical autonomy. AMOS introduces a novel, streamlined skill management concept for exploration missions featuring comprehensive training and guidance modules for ultrasound examinations using the ISS Ultrasound 2 (a modified GE Vivid-q™; General Electric HealthCare, Chicago, IL). With no prior crew training or remote guidance, two Tech Demos on the ISS (April 2020 and June 2022) resulted in high quality, clinically useful image sets. We will provide a review of historical, current, and planned medical devices and technologies considered for inclusion within future spaceflight medical systems and summarize hardware development activities and medical device tech demos conducted on the ISS.

Astronaut health and performance↗

Effects of the hindlimb-unloading model of spaceflight conditions on resistance of mice to infection with Klebsiella pneumoniae

BACKGROUND: It has been well documented in several studies that many immunologic parameters are altered in experimental animals and human subjects who have flown in space. However, it is not fully known whether these immunologic changes could result in increased susceptibility to infection. Hindlimb (antiorthostatic) unloading of rodents has been used successfully to simulate some of the effects of spaceflight on physiologic systems. OBJECTIVE: The objective of this study was to determine the effect of hindlimb unloading on the outcome of Klebsiella pneumoniae infection in mice. METHODS: Hindlimb-unloaded, hindlimb-restrained, and control mice were intraperitoneally infected with one 50% lethal dose of K pneumoniae 2 days after suspension. Mortality and bacterial load in several organs were compared among the groups. RESULTS: Unloaded mice showed significantly increased mortality and reduced mean time to death compared with that seen in the control groups. Kinetics of bacterial growth with smaller infective doses revealed that control mice were able to clear bacteria from the organs after 30 hours. In contrast, unloaded mice had continued bacterial growth at the same time point. CONCLUSION: The results of this study suggest that hindlimb unloading might enhance the dissemination of K pneumoniae, leading to increased mortality. The complex physiologic changes observed during hindlimb unloading, including stress, have a key role in the pathophysiology of this infection.

NASA Discipline Regulatory Physiology↗

Expression and structure of the Chlamydia trachomatis DksA ortholog

Chlamydia trachomatis is a bacterial obligate intracellular parasite and a significant cause of human disease, including sexually transmitted infections and trachoma. The bacterial RNA polymerase-binding protein DksA is a transcription factor integral to the multicomponent bacterial stress response pathway known as the stringent response. The genome of C. trachomatis encodes a DksA ortholog (DksA Ct ) that is maximally expressed at 15–20 h post infection, a time frame correlating with the onset of transition between the replicative reticulate body (RB) and infectious elementary body (EB) forms of the pathogen. Ectopic overexpression of DksA Ct in C. trachomatis prior to RB–EB transitions during infection of HeLa cells resulted in a 39.3% reduction in overall replication (yield) and a 49.6% reduction in recovered EBs. While the overall domain organization of DksA Ct is similar to the DksA ortholog of Escherichia coli (DksA Ec ), DksA Ct did not functionally complement DksA Ec . Transcription of dksA Ct is regulated by tandem promoters, one of which also controls expression of nrdR, encoding a negative regulator of deoxyribonucleotide biosynthesis. The phenotype resulting from ectopic expression of DksA Ct and the correlation between dksA Ct and nrdR expression is consistent with a role for DksA Ct in the C. trachomatis developmental cycle.

59 BASIC BIOLOGICAL SCIENCES↗

VIBES: a workflow for annotating and visualizing viral sequences integrated into bacterial genomes

Abstract Bacteriophages are viruses that infect bacteria. Many bacteriophages integrate their genomes into the bacterial chromosome and become prophages. Prophages may substantially burden or benefit host bacteria fitness, acting in some cases as parasites and in others as mutualists. Some prophages have been demonstrated to increase host virulence. The increasing ease of bacterial genome sequencing provides an opportunity to deeply explore prophage prevalence and insertion sites. Here we present VIBES (Viral Integrations in Bacterial genomES), a workflow intended to automate prophage annotation in complete bacterial genome sequences. VIBES provides additional context to prophage annotations by annotating bacterial genes and viral proteins in user-provided bacterial and viral genomes. The VIBES pipeline is implemented as a Nextflow-driven workflow, providing a simple, unified interface for execution on local, cluster and cloud computing environments. For each step of the pipeline, a container including all necessary software dependencies is provided. VIBES produces results in simple tab-separated format and generates intuitive and interactive visualizations for data exploration. Despite VIBES’s primary emphasis on prophage annotation, its generic alignment-based design allows it to be deployed as a general-purpose sequence similarity search manager. We demonstrate the utility of the VIBES prophage annotation workflow by searching for 178 Pf phage genomes across 1072 Pseudomonas spp. genomes.

59 BASIC BIOLOGICAL SCIENCES↗

Effects of Eimeria acervulina infection on the luminal and mucosal microbiota of the cecum and ileum in broiler chickens

Coccidiosis, an intestinal disease caused by Eimeria parasites, is responsible for major losses in the poultry industry by impacting chicken health. The gut microbiota is associated with health factors, such as nutrient exchange and immune system modulation, requiring understanding on the effects of Eimeria infection on the gut microbiota. This study aimed to determine the effects of Eimeria acervulina infection on the luminal and mucosal microbiota of the cecum (CeL and CeM) and ileum (IlL and IlM) at multiple time points (days 3, 5, 7, 10, and 14) post-infection. E. acervulina infection decreased evenness in CeL microbiota at day 10, increased richness in CeM microbiota at day 3 before decreasing richness at day 14, and decreased richness in IlL microbiota from day 3 to 10. CeL, CeM, and IlL microbiota differed between infected and control birds based on beta diversity at varying time points. Infection reduced relative abundance of bacterial taxa and some predicted metabolic pathways known for short-chain fatty acid production in CeL, CeM, and IlL microbiota, but further understanding of metabolic function is required. Despite E. acervulina primarily targeting the duodenum, our findings demonstrate the infection can impact bacterial diversity and abundance in the cecal and ileal microbiota.

59 BASIC BIOLOGICAL SCIENCES↗

Spaceflight and Simulated Microgravity Increases Virulence of the Known Bacterial Pathogen S. Marcescens

After spaceflight, the number of immune cells is reduced in humans. In other research models, including Drosophila, not only is there a reduction in the number of plasmatocytes, but expression of immune-related genes is also changed after spaceflight. These observations suggest that the immune system is compromised after exposure to microgravity. It has also been reported that there is a change in virulence of some bacterial pathogens after spaceflight. We recently observed that samples of gram-negative S. marcescens retrieved from spaceflight is more virulent than ground controls, as determined by reduced survival and increased bacterial growth in the host. We were able to repeat this finding of increased virulence after exposure to simulated microgravity using the rotating wall vessel, a ground based analog to microgravity. With the ground and spaceflight samples, we looked at involvement of the Toll and Imd pathways in the Drosophila host in fighting infection by ground and spaceflight samples. We observed that Imd-pathway mutants were more susceptible to infection by the ground bacterial samples, which aligns with the known role of this pathway in fighting infections by gram-negative bacteria. When the Imd-pathway mutants were infected with the spaceflight sample, however, they exhibited the same susceptibility as seen with the ground control bacteria. Interestingly, all mutant flies show the same susceptibility to the spaceflight bacterial sample as do wild type flies. This suggests that neither humoral immunity pathway is effectively able to counter the increased pathogenicity of the space-flown S. marcescens bacteria.

immunity↗

Discovery of GuaB inhibitors with efficacy against Acinetobacter baumannii infection

ABSTRACT Guanine nucleotides are required for growth and viability of cells due to their structural role in DNA and RNA, and their regulatory roles in translation, signal transduction, and cell division. The natural antibiotic mycophenolic acid (MPA) targets the rate-limiting step inde novoguanine nucleotide biosynthesis executed by inosine-5´-monophosphate dehydrogenase (IMPDH). MPA is used clinically as an immunosuppressant, but whetherin vivoinhibition of bacterial IMPDH (GuaB) is a valid antibacterial strategy is controversial. Here, we describe the discovery of extremely potent small molecule GuaB inhibitors (GuaBi) specific to pathogenic bacteria with a low frequency of on-target spontaneous resistance and bactericidal efficacyin vivoagainstAcinetobacter baumanniimouse models of infection. The spectrum of GuaBi activity includes multidrug-resistant pathogens that are a critical priority of new antibiotic development. Co-crystal structures ofA. baumannii, Staphylococcus aureus, andEscherichia coliGuaB proteins bound to inhibitors show comparable binding modes of GuaBi across species and identifies key binding site residues that are predictive of whole-cell activity across both Gram-positive and Gram-negative clades of Bacteria. The clearin vivoefficacy of these small molecule GuaB inhibitors in a model ofA. baumanniiinfection validates GuaB as an essential antibiotic target. IMPORTANCE The emergence of multidrug-resistant bacteria worldwide has renewed interest in discovering antibiotics with novel mechanism of action. For the first time ever, we demonstrate that pharmacological inhibition ofde novoguanine biosynthesis is bactericidal in a mouse model ofAcinetobacter baumanniiinfection. Structural analyses of novel inhibitors explain differences in biochemical and whole-cell activity across bacterial clades and underscore why this discovery may have broad translational impact on treatment of the most recalcitrant bacterial infections.

Microbiology↗

Activation of CBASS Cap5 endonuclease immune effector by cyclic nucleotides

The bacterial cyclic oligonucleotide-based antiphage signaling system (CBASS) is similar to the cGAS–STING system in humans, containing an enzyme that synthesizes a cyclic nucleotide on viral infection and an effector that senses the second messenger for the antiviral response. Cap5, containing a SAVED domain coupled to an HNH DNA endonuclease domain, is the most abundant CBASS effector, yet the mechanism by which it becomes activated for cell killing remains unknown. We present here high-resolution structures of full-length Cap5 from Pseudomonas syringae (Ps) with second messengers. Here, the key to PsCap5 activation is a dimer-to-tetramer transition, whereby the binding of second messenger to dimer triggers an open-to-closed transformation of the SAVED domains, furnishing a surface for assembly of the tetramer. This movement propagates to the HNH domains, juxtaposing and converting two HNH domains into states for DNA destruction. These results show how Cap5 effects bacterial cell suicide and we provide proof-in-principle data that the CBASS can be extrinsically activated to limit bacterial infections.

36 MATERIALS SCIENCE↗

Dynamics of phage-host interactions in Bacteroides fragilis resolved by single-cell transcriptomics

The interactions between lytic phages and their hosts are typically studied in bulk culture, which obscures cell-cell differences in infection susceptibility or expression of protective factors. Here, we use bacterial single-cell RNA sequencing to profile the transcriptomes of ~50,000 cells from cultures of a human pathobiont, Bacteroides fragilis, infected with a lytic bacteriophage. From a single sampling, we quantified the asynchronous progression of phage infection in individual bacterial cells and reconstructed the infection timeline, characterizing both host and phage transcriptomic changes as infection unfolded. Further, we discovered phenotypic subpopulations of bacteria that remained uninfected. Each cell’s vulnerability to phage infection was influenced by expression of multiple genetic loci, most prominently phase-variable capsular polysaccharide (CPS) biosynthesis pathways and an operon predicted to encode fimbrial genes. These findings uncovered genome-wide phase variation and stochasticity that enable bacterial survival and re-growth without acquiring additional mutations. Overall, we establish bacterial single-cell RNA sequencing as a powerful platform for investigating the dynamics of host-phage interactions and revealing the roles of phase variation and stochasticity in bacterial defenses.

Bacteria↗

2-deoxy-D-glucose-induced metabolic stress enhances resistance to Listeria monocytogenes infection in mice

Exposure to different forms of psychological and physiological stress can elicit a host stress response, which alters normal parameters of neuroendocrine homeostasis. The present study evaluated the influence of the metabolic stressor 2-deoxy-D-glucose (2-DG; a glucose analog, which when administered to rodents, induces acute periods of metabolic stress) on the capacity of mice to resist infection with the facultative intracellular bacterial pathogen Listeria monocytogenes. Female BDF1 mice were injected with 2-DG (500 mg/kg b. wt.) once every 48 h prior to, concurrent with, or after the onset of a sublethal dose of virulent L. monocytogenes. Kinetics of bacterial growth in mice were not altered if 2-DG was applied concurrently or after the start of the infection. In contrast, mice exposed to 2-DG prior to infection demonstrated an enhanced resistance to the listeria challenge. The enhanced bacterial clearance in vivo could not be explained by 2-DG exerting a toxic effect on the listeria, based on the results of two experiments. First, 2-DG did not inhibit listeria replication in trypticase soy broth. Second, replication of L. monocytogenes was not inhibited in bone marrow-derived macrophage cultures exposed to 2-DG. Production of neopterin and lysozyme, indicators of macrophage activation, were enhanced following exposure to 2-DG, which correlated with the increased resistance to L. monocytogenes. These results support the contention that the host response to 2-DG-induced metabolic stress can influence the capacity of the immune system to resist infection by certain classes of microbial pathogens.

Non-NASA Center↗

Shifts in the swine nasal microbiota following Bordetella bronchiseptica challenge in a longitudinal study

Bordetella bronchiseptica is a widespread, highly infectious bacterial pathogen that causes respiratory disease in swine and increases the severity of respiratory infections caused by other viral or bacterial pathogens. However, the impact of B. bronchiseptica infection on the swine respiratory microbiota has not been thoroughly investigated. Here, we aim to assess the influence of B. bronchiseptica infection on the community structure and abundance of members of the swine nasal microbiota. To do so, the nasal microbiota of a non-infected control group and a group infected with B. bronchiseptica (BB group) were characterized prior to B. bronchiseptica strain KM22 challenge (day 0) and on selected days in the weeks following B. bronchiseptica challenge (days 1, 3, 7, 10, 14, 21, 36, and 42). Bordetella bronchiseptica was cultured from nasal samples of the BB group to assess nasal colonization. The results showed that B. bronchiseptica colonization did not persistently affect the nasal bacterial diversity of either of the treatment groups (alpha diversity). However, the bacterial community structures (beta diversity) of the two treatment groups significantly diverged on day 7 when peak colonization levels of B. bronchiseptica were detected. This divergence continued through the last sampling time point. In addition, Pasteurella, Pasteurellaceae (unclassified), Mycoplasma, Actinobacillus, Streptococcus, Escherichia-Shigella, and Prevotellaceae (unclassified) showed increased abundances in the BB group relative to the control group at various time points. This study revealed that B. bronchiseptica colonization can disturb the upper respiratory tract microbiota, and further research is warranted to assess how these disturbances can impact susceptibility to secondary infections by other respiratory pathogens.

59 BASIC BIOLOGICAL SCIENCES↗

Hi-C metagenome sequencing reveals soil phage–host interactions

Abstract Bacteriophages are abundant in soils. However, the majority are uncharacterized, and their hosts are unknown. Here, we apply high-throughput chromosome conformation capture (Hi–C) to directly capture phage-host relationships. Some hosts have high centralities in bacterial community co-occurrence networks, suggesting phage infections have an important impact on the soil bacterial community interactions. We observe increased average viral copies per host (VPH) and decreased viral transcriptional activity following a two-week soil-drying incubation, indicating an increase in lysogenic infections. Soil drying also alters the observed phage host range. A significant negative correlation between VPH and host abundance prior to drying indicates more lytic infections result in more host death and inversely influence host abundance. This study provides empirical evidence of phage-mediated bacterial population dynamics in soil by directly capturing specific phage-host interactions.

59 BASIC BIOLOGICAL SCIENCES↗

Breaking the Ice: A Review of Phages in Polar Ecosystems

Bacteriophages, or phages, are viruses that infect and replicate within bacterial hosts, playing a significant role in regulating microbial populations and ecosystem dynamics. However, phages from extreme environments such as polar regions remain relatively understudied due to challenges such as restricted ecosystem access and low biomass. In this study, understanding the diversity, structure, and functions of polar phages is crucial for advancing our knowledge of the microbial ecology and biogeochemistry of these environments. In this review, we will explore the current state of knowledge on phages from the Arctic and Antarctic, focusing on insights gained from -omic studies, phage isolation, and virus-like particle abundance data. Metagenomic studies of polar environments have revealed a high diversity of phages with unique genetic characteristics, providing insights into their evolutionary and ecological roles. Phage isolation studies have identified novel phage–host interactions and contributed to the discovery of new phage species. Virus-like particle abundance and lysis rate data, on the other hand, have highlighted the importance of phages in regulating bacterial populations and nutrient cycling in polar environments. Overall, this review aims to provide a comprehensive overview of the current state of knowledge about polar phages, and by synthesizing these different sources of information, we can better understand the diversity, dynamics, and functions of polar phages in the context of ongoing climate change, which will help to predict how polar ecosystems and residing phages may respond to future environmental perturbations.

09 BIOMASS FUELS↗

Metabolic multistability and hysteresis in a model aerobe-anaerobe microbiome community

Major changes in the microbiome are associated with health and disease. Some microbiome states persist despite seemingly unfavorable conditions, such as the proliferation of aerobe-anaerobe communities in oxygen-exposed environments in wound infections or small intestinal bacterial overgrowth. Mechanisms underlying transitions into and persistence of these states remain unclear. Using two microbial taxa relevant to the human microbiome, we combine genome-scale mathematical modeling, bioreactor experiments, transcriptomics, and dynamical systems theory to show that multistability and hysteresis (MSH) is a mechanism describing the shift from an aerobe-dominated state to a resilient, paradoxically persistent aerobe-anaerobe state. We examine the impact of changing oxygen and nutrient regimes and identify changes in metabolism and gene expression that lead to MSH and associated multi-stable states. In such systems, conceptual causation-correlation connections break and MSH must be used for analysis. Using MSH to analyze microbiome dynamics will improve our conceptual understanding of stability of microbiome states and transitions between states.

59 BASIC BIOLOGICAL SCIENCES↗