Biology subjects

Huang, K.

Publications and source records attributed to Huang, K..

At least 181 records · Page 10Linked to original sources

bioRxiv2020

Auxin Regulation and MdPIN Expression during Adventitious Root Initiation in Apple Cuttings

Adventitious root (AR) formation is critical for the efficient propagation of elite horticultural and forestry crops. Despite decades of research, the cellular processes and molecular mechanisms underlying AR induction in woody plants remains obscure. We examined the details of AR formation in the apple (Malus domestica) M.9 rootstock, the most widely used dwarf rootstock for intensive production, and investigated the role of polar auxin transport in post-embryonic organogenesis. AR formation begins with a series of founder cell divisions and elongation of interfascicular cambium adjacent to vascular tissues. This process was associated with a relatively high indole acetic acid (IAA) content and hydrolysis of starch grains. Exogenous auxin treatment promoted cell division, as well as the proliferation and reorganization of the endoplasmic reticulum and Golgi membrane. By contrast, treatment with the auxin transport inhibitor N-1-naphthylphthalamic acid (NPA) inhibited cell division in the basal region of the cutting and resulted in abnormal cell divisions during early AR formation. In addition, PIN-FORMED (PIN) transcripts were expressed differentially throughout the whole AR development process, with the up-regulation of MdPIN8 and MdPIN10 during induction, an up-regulation of MdPIN4, MdPIN5 and MdPIN8 during extension, and an up-regulation of all MdPINs during AR initiation. This research provides a deeper understanding of the cellular and molecular underpinnings of the AR process in woody plants.

plant biology↗

bioRxiv2020

The dominance hierarchy of the female Yunnan snub-nosed monkeys (Rhinopithecus bieti)

Dominance hierarchies are common in social mammals, especially primates. The formation of social hierarchies is conducive to solving the problem of the allocation of scarce resources among individuals. From August 2015 to July 2016, we observed a wild, provisioned Yunnan snub-nosed monkey (Rhinopithecus bieti) group at Xiangguqing in Baimaxueshan National Nature Reserve, Yunnan Province, China. Aggressive and submissive behaviors were used to investigate dominance hierarchies between female individuals in the same one-male unit (OMU), and the grooming reciprocity index was used to detect reciprocal relationships between these females within the OMU. The results showed that loose social hierarchies exist among the females in each OMU, and more dominant individuals have higher grooming incomes. These results are consistent with the aggressive-submissive hypothesis and the resource control hypothesis.

animal behavior and cognition↗

bioRxiv2020

Persistent cell proliferation signals correlates with increased glycolysis in tumor hypoxia microenvironment across cancer types

BackgroundAltered metabolism is a hallmark of cancer and glycolysis is one of the important factors promoting tumor development. Given that the absence of multi-sample big data research about glycolysis, the molecular mechanisms involved in glycolysis or the relationships between glycolysis and tumor microenvironment are not fully studied. Thus, a more comprehensive approach in a pan-cancer landscape may be needed. MethodsHere, we develop a computational pipeline to study multi-omics molecular features defining glycolysis activity and identify molecular alterations that correlate with glycolysis. We apply a 22-gene expression signature to define the glycolysis activity landscape and verify the robustness using clinically defined glycolysis samples from several previous studies. Based on gene expression signature, we classify about 5552 of 9229 tumor samples into glycolysis score-high and score-low groups across 25 cancer types from The Cancer Genome Atlas (TCGA) and demonstrate their prognostic associations. Moreover, using genomes and transcriptome data, we characterize the association of copy-number aberrations (CNAs), somatic single-nucleotide variants (SNVs) and hypoxia signature with glycolysis activity. FindingsGene set variation analysis (GSVA) score by gene set expression was verified robustly to represent glycolytic activity and highly glycolytic tumors presented a poor overall survival in some cancer types. Then, we identified various types of molecular features promoting tumor cell proliferation were associated with glycolysis activity. Our study showed that TCA cycle and respiration electron transport were active in glycolysis-high tumors, indicating glycolysis was not a symptom of impaired oxidative metabolism. The glycolytic score significantly correlated with hypoxia score across all cancer types. Glycolysis score was also associated with elevated genomic instability. In all tumor types, high glycolysis tumors exhibited characteristic driver genes altered by CNAs identified multiple oncogenes and tumor suppressors. We observed widespread glycolysis-associated dysregulation of mRNA across cancers and screened out HSPA8 and P4HA1 as the potential modulating factor to glycolysis. Besides, the expression of genes encoding glycolytic enzymes positively correlated with genes in cell cycle. InterpretationThis is the first study to identify gene expression signatures that reflect glycolysis activity, which can be easily applied to large numbers of patient samples. Our analysis establishes a computational framework for characterizing glycolysis activity using gene expression data and defines correlation of glycolysis with the hypoxia microenvironment, tumor cell cycle and proliferation at a pan-cancer landscape. The findings suggest that the mechanisms whereby hypoxia influence glycolysis are likely multifactorial. Our finding is significant not just in demonstrating definition value for glycolysis but also in providing a comprehensive molecular-level understanding of glycolysis and suggesting a framework to guide combination therapy that may block the glycolysis pathway to control tumor growth in hypoxia microenvironment.

cancer biology↗

bioRxiv2020

A deep learning approach for tissue spatial quantification and genomic correlations of histopathological images

Epithelial and stromal tissue are components of the tumor microenvironment and play a major role in tumor initiation and progression. Distinguishing stroma from epithelial tissues is critically important for spatial characterization of the tumor microenvironment. We propose an image analysis pipeline based on a Convolutional Neural Network (CNN) model to classify epithelial and stromal regions in whole-slide images. The CNN model was trained using well-annotated breast cancer tissue microarrays and validated with images from The Cancer Genome Atlas (TCGA) project. Our model achieves a classification accuracy of 91.02%, which outperforms other state-of-the-art methods. Using this model, we generated pixel-level epithelial/stromal tissue maps for 1,000 TCGA breast cancer slide images that are paired with gene expression data. We subsequently estimated the epithelial and stromal ratios and performed correlation analysis to model the relationship between gene expression and tissue ratios. Gene Ontology enrichment analyses of genes that were highly correlated with tissue ratios suggest the same tissue was associated with similar biological processes in different breast cancer subtypes, whereas each subtype had its own idiosyncratic biological processes governing the development of these tissues. Taken all together, our approach can lead to new insights in exploring relationships between image-based phenotypes and their underlying genomic data and biological processes for all types of solid tumors.

bioinformatics↗

bioRxiv2020

X-chromosome dosage compensation dynamics in human early embryos

In mammals, female cells are obliged to inactivate one of two X chromosomes to achieve dosage parity with the single X chromosome in male cells, and it is also thought that the single active X chromosome is increased 2-fold to achieve dosage balance with two sets of autosomes (X:A ratio = 1, or Ohnos hypothesis). However, the ontogeny of X-chromosome inactivation and augmentation of the single active X remains unclear during human embryogenesis. Here, we perform single-cell RNA-seq analysis to examine the timing of X:A balancing and X-inactivation (XCI) in pre- and peri-implantation human embryos up to fourteen days in culture. We find that X-chromosome gene expression in both male and female preimplantation embryos is approximately balanced with autosomes (X:A ratio = 1) after embryonic genome activation (EGA) and persists through fourteen days in vitro. Cross-species analysis of preimplantation embryo also show balanced X:A ratio within the first few days of development. By single-cell mRNA SNP profiling, we find XCI beginning in day 6-7 blastocyst embryos, but does not affect X:A dosage balance. XCI is most evident in trophoectoderm (TE) cells, but can also be observed in a small number of inner cell mass (ICM)-derived cells including primitive endoderm (PE) and epiblast (EPI) cells. Analysis between individual XaXa and XaXi sister cells from the same embryo reveals random XCI and persistently balanced X:A ratio, including sister cells transitioning between XaXa and XaXi states. We therefore conclude that the male X-chromosome undergoes X chromosome augmentation prior to the simultaneous X-chromosome inactivation and augmentation in females. Together, our data demonstrate an evolutionally conserved model of X chromosome dosage compensation in humans and other mammalian species.

developmental biology↗

bioRxiv2020

In vitro biosynthesis of poly-β-1,4-glucan derivatives using a promiscuous glycosyltransferase

The {beta}-1,4-glucose linkage of cellulose is the most abundant polymeric linkage on earth and as such is of considerable interest in biology and biotechnology. It remains challenging to synthesize this linkage in vitro due to a lack of suitable biocatalysts; the natural cellulose biosynthetic machinery is a membrane-associated complex with processive activity that cannot be easily manipulated to synthesize tailor-made oligosaccharides and their derivatives. Here we identify a promiscuous activity of a soluble recombinant biocatalyst, Neisseria meningitidis glycosyltransferase LgtB, suitable for the polymerization of glucose from UDP-glucose via the generation of {beta}-1,4-glycosidic linkages. We employed LgtB to synthesize natural and derivatized cello-oligosaccharides and we demonstrate how LgtB can be incorporated in biocatalytic cascades and chemo-enzymatic strategies to synthesize cello-oligosaccharides with tailored functionalities. We also show how the resulting glycan structures can be applied as chemical probes to report on activity and selectivity of plant cell wall degrading enzymes, including lytic polysaccharide monooxygenases. We anticipate that this biocatalytic approach to derivatized cello-oligosaccharides via glucose polymerization will open up new applications in biology and nanobiotechnology.

biochemistry↗

bioRxiv2020

Nanoscale Chromatin Imaging and Analysis (nano-ChIA) platform bridges 4-D chromatin organization with molecular function

In eukaryotic cells, chromatin structure is linked to transcription processes through the regulation of genome organization. Extending across multiple length-scales - from the nucleosome to higher-order three-dimensional structures - chromatin is a dynamic system which evolves throughout the lifetime of a cell. However, no individual technique can fully elucidate the behavior of chromatin organization and its relation to molecular function at all length- and timescales at both a single-cell and a cell population level. Herein, we present a multi-technique nanoscale Chromatin Imaging and Analysis (nano-ChIA) platform that bridges electron tomography and optical superresolution imaging of chromatin conformation and transcriptional processes, with resolution down to the level of individual nucleosomes, with high-throughput, label-free analysis of chromatin packing and its dynamics in live cells. Utilizing nano-ChIA, we observed that chromatin is localized into spatially separable packing domains, with an average diameter of around 200 nm, sub-Mb genomic size, and an internal fractal structure. The chromatin packing behavior of these domains is directly influenced by active gene transcription. Furthermore, we demonstrated that the chromatin packing domain structure is correlated among progenitor cells and all their progeny, indicating that the organization of chromatin into fractal packing domains is heritable across cell division. Further studies employing the nano-ChIA platform have the potential to provide a more coherent picture of chromatin structure and its relation to molecular function.

genomics↗

bioRxiv2020

Virtual-freezing fluorescence imaging flow cytometry

By virtue of the combined merits of flow cytometry and fluorescence microscopy, imaging flow cytometry (IFC) has become an established tool for cell analysis in diverse biomedical fields such as cancer biology, microbiology, immunology, hematology, and stem cell biology. However, the performance and utility of IFC are severely limited by the fundamental trade-off between throughput, sensitivity, and spatial resolution. For example, at high flow speed (i.e., high throughput), the integration time of the image sensor becomes short, resulting in reduced sensitivity or pixel resolution. Here we present an optomechanical imaging method that overcomes the trade-off by virtually "freezing" the motion of flowing cells on the image sensor to effectively achieve 1,000 times longer exposure time for microscopy-grade fluorescence image acquisition. Consequently, it enables high-throughput IFC of single cells at >10,000 cells/s without sacrificing sensitivity and spatial resolution. The availability of numerous information-rich fluorescence cell images allows high-dimensional statistical analysis and accurate classification with deep learning, as evidenced by our demonstration of unique applications in hematology and microbiology.

cell biology↗

bioRxiv2019

Deoxynivalenol Promotes Porcine Epidemic Diarrhea Virus Infection and Aggravates Gut Barrier Injury

Porcine epidemic diarrhea virus (PEDV) is a highly contagious pathogenic virus that causes severe diarrhea and dehydration in pigs of all ages. Deoxynivalenol (DON), the most abundant trichothecene in food and feed, causes vomit and diarrhea in animals and human. However, whether DON exposure could affect PEDV infection remains unknown. Herein, we investigated the impacts of DON on entry and replication of PEDV, morbidity situation of piglets and the mechanisms involved. In vivo, twenty-seven piglets infected naturally with PEDV were randomly divided into three groups, receiving the basal diet containing 0, 750 and 1500 g/kg DON, respectively. We observed significant increases in the diarrhea rates, the villous injury of jejunums and the PEDV proliferation of duodenum, jejunum, ileum and mesenterium of piglets in experimental groups compared with control. Additionally, the autophagosome-like vesicles and the autophagy-related protein expressions were also increased in experimental groups. In vitro, we observed that, approximately 2 hrs post-infection, 0.1, 0.5 and 1.0 M DON promoted PEDV entry (P < 0.05) in IPEC-J2s and resulted in tight junction protein occludin internalization. Knockdown of occludin and CRISPR-Cas9-mediated knockout of LC3B indicated a vital role of autophagy-induced occludin internalization in DON-promoted PEDV entry. We also observed that, 24 hrs post-infection, a significant increase in PEDV replication after 0.1, 0.5 and 1.0 M DON treatment, along with the induction of a complete autophagy. Specifically, deletion of LC3B indicated a crucial role of autophagy in DON-promoted PEDV replication. Pretreatment with SB202190, a p38 signaling inhibitor, abolished the induction of autophagy. Furthermore, downregulation of type I interferon revealed that DON contributed PEDV to escape innate immune. Mechanistically, DON-caused innate immune escape was related to the upregulation of LC3B, which further inhibited STING phosphorylation. Taken together, DON could promote PEDV infection by inducing occludin internalization and innate immune escape via triggering p38-mediated autophagy. Author summaryPorcine epidemic diarrhea (PED), a devastating enteric disease, leads to catastrophic economic loss to the global pig industry. Its primary pathogen is the coronavirus PED virus (PEDV). Growing evidence indicates that pathogen infection is not the only factor of PED outbreaks, other non-infectious factors is also related to this disease. We guessed some ubiquitous substances, such as deoxynivalenol (DON), that lead to pig intestinal epithelial cell stress might encourage the progress and spread of PED. In the present study, the weaning piglets infected naturally with PEDV and the IPEC-J2 cell line were selected as models to explore the effects of DON on PEDV infection, morbidity and gut barrier. Our results showed that DON exposure can promote PEDV infection in vitro and in vivo, and the underlying mechanism might be related to LC3B-mediated autophagy. Our findings reveal new pathways for developing potential novel antiviral strategies against PEDV infection.

immunology↗

bioRxiv2019

Attenuation of epigenetic regulator SMARCA4 and ERK-ETS signaling suppresses aging-related dopaminergic degeneration

Parkinsons disease (PD) is a complex disease with high heterogeneity. How complex interactions of genetic, environmental factors and aging jointly contribute to dopaminergic degeneration in PD is largely unclear. Here, we applied frequent gene co-expression analysis on human patient substantia nigra-specific microarray datasets to identify potential novel disease-related genes. In vivo Drosophila studies validated two of 32 candidate genes, a chromatin remodeling factor SMARCA4 and a biliverdin reductase BLVRA. Inhibition of SMARCA4 was able to prevent dopaminergic degeneration not only caused by overexpression of BLVRA but also in four most common Drosophila PD models. Mechanistically, aberrant SMARCA4 and BLVRA converged on elevated ERK-ETS activity, attenuation of which by either genetic or pharmacological manipulation effectively suppressed dopaminergic degeneration in vivo. Drug inhibition of MEK/ERK also mitigated mitochondrial defects in PD gene-deficient human cells. Our findings underscore the important role of epigenetic regulators and implicate a common signaling axis for therapeutic intervention in a broad range of aging-related disorders including PD.

neuroscience↗

bioRxiv2019

Transcriptome-wide transmission disequilibrium analysis identifies novel risk genes for autism spectrum disorder

Recent advances in consortium-scale genome-wide association studies (GWAS) have highlighted the involvement of common genetic variants in autism spectrum disorder (ASD), but our understanding of their etiologic roles, especially the interplay with rare variants, is incomplete. In this work, we introduce an analytical framework to quantify the transmission disequilibrium of genetically regulated gene expression from parents to offspring. We applied this framework to conduct a transcriptome-wide association study (TWAS) on 7,805 ASD proband-parent trios, and replicated our findings using 35,740 independent samples. We identified 31 associations at the transcriptome-wide significance level. In particular, we identified POU3F2 (p=2.1e-7), a transcription factor (TF) mainly expressed in developmental brain. TF targets regulated by POU3F2 showed a 2.1-fold enrichment for known ASD genes (p=4.6e-5) and a 2.7-fold enrichment for loss-of-function de novo mutations in ASD probands (p=7.1e-5). These results provide a clear example of the connection between ASD genes affected by very rare mutations and an unlinked key regulator affected by common genetic variations.

genetics↗

bioRxiv2019

Multiple chromosomal inversions contribute to adaptive divergence of a dune sunflower ecotype

Both models and case studies suggest that chromosomal inversions can facilitate adaptation and speciation in the presence of gene flow by suppressing recombination between locally adapted alleles. Until recently, however, it has been laborious and time-consuming to identify and genotype inversions in natural populations. Here we apply RAD sequencing data and newly developed population genomic approaches to identify putative inversions that differentiate a sand dune ecotype of the prairie sunflower (Helianthus petiolaris) from populations found on the adjacent sand sheet. We detected seven large genomic regions that exhibit a different population structure than the rest of the genome and that vary in frequency between dune and non-dune populations. These regions also show high linkage disequilibrium and high heterozygosity between, but not within haplotypes, consistent with the behavior of large inversions, an inference subsequently validated in part by comparative genetic mapping. Genome-environment association analyses show that key environmental variables, including vegetation cover and soil nitrogen, are significantly associated with inversions. The inversions co-locate with previously described \"islands of differentiation,\" and appear to play an important role in adaptive divergence and incipient speciation within H. petiolaris.

evolutionary biology↗

bioRxiv2019

Massive haplotypes underlie ecotypic differentiation in sunflowers

Species often include multiple ecotypes that are adapted to different environments. But how do ecotypes arise, and how are their distinctive combinations of adaptive alleles maintained despite hybridization with non-adapted populations? Re-sequencing of 1506 wild sunflowers from three species identified 37 large (1-100 Mbp), non-recombining haplotype blocks associated with numerous ecologically relevant traits, and soil and climate characteristics. Limited recombination in these regions keeps adaptive alleles together, and we find that they differentiate several sunflower ecotypes; for example, they control a 77 day difference in flowering between ecotypes of silverleaf sunflower (likely through deletion of a FLOWERING LOCUS T homolog), and are associated with seed size, flowering time and soil fertility in dune-adapted sunflowers. These haplotypes are highly divergent, associated with polymorphic structural variants, and often appear to represent introgressions from other, possibly extinct, congeners. This work highlights a pervasive role of structural variation in maintaining complex ecotypic adaptation.

evolutionary biology↗

bioRxiv2019

Rapid ordering of barcoded transposon insertion libraries of anaerobic bacteria

Commensal bacteria from the human intestinal microbiota play important roles in health and disease. Research into the mechanisms by which these bacteria exert their effects is hampered by the complexity of the microbiota and by the strict growth requirements of the individual species. The assembly of ordered transposon insertion libraries, in which nearly all nonessential genes have been disrupted and the strains stored as independent monocultures, would be a transformative resource for research into many microbiota members. However, assembly of these libraries must be fast and inexpensive in order to empower investigation of the large number of species that typically compose gut communities. The methods used to generate ordered libraries must also be adapted to the anaerobic growth requirements of most intestinal bacteria. We have developed a protocol to assemble ordered libraries of transposon insertion mutants that is fast, cheap, and effective for even strict anaerobes. The protocol differs from currently available methods by making use of cell sorting to order the library and barcoded transposons to facilitate the localization of ordered mutations in the library. By tracking transposon insertions using barcode sequencing, our approach increases the accuracy and reduces the time and effort required to locate mutants in the library. Ordered libraries can be sorted and characterized over the course of two weeks using this approach. We expect this protocol will lower the barrier to generating comprehensive, ordered mutant libraries for many species in the human microbiota, allowing for new investigations into genotype-phenotype relationships within this important microbial ecosystem.

genetics↗

bioRxiv2019

TSUNAMI: Translational Bioinformatics Tool Suite For Network Analysis And Mining

Gene co-expression network (GCN) mining identifies gene modules with highly correlated expression profiles across samples/conditions. It helps to discover latent gene/molecular interactions, identify novel gene functions, and extract molecular features from certain disease/condition groups, thus help to identify disease biomarkers. However, there lacks an easy-to-use tool package for users to mine GCN modules that are relatively small in size with tightly connected genes that can be convenient for downstream Gene Ontology (GO) enrichment analysis, as well as modules that may share common members. To address this need, we develop a GCN mining tool package TSUNAMI (Tools SUite for Network Analysis and MIning) which incorporates our state-of-the-art lmQCM algorithm to mine GCN modules in public and user-input data (microarray, RNA-seq, or any other numerical omics data), then performs downstream GO and enrichment analysis based on the modules identified. It has several features and advantages: (i) user friendly interface and the real-time co-expression network mining through web server; (ii) direct access and search of GEO and TCGA databases as well as user-input expression matrix (microarray, RNA-seq, etc.) for GCN module mining; (iii) multiple co-expression analysis tools to choose with highly flexible of parameter selection options; (iv) identified GCN modules are summarized to eigengenes, which are convenient for user to check their correlation with other clinical traits; (v) integrated downstream Enrichr enrichment analysis and links to other GO tools; (vi) visualization of gene loci by Circos plot in any step. The web service is freely accessible through URL: http://spore.ph.iu.edu:3838/zhihuan/TSUNAMI/. Source code is available at https://github.com/huangzhii/TSUNAMI/.

bioinformatics↗

bioRxiv2019

Glutamatergic and GABAergic neuronal populations in thedorsolateral Periacqueductual Gray have differentfunctional roles in fear conditioning

It is though that only a subset of brain structures can encode emotional states. This can be investigated though a set of properties, including the ability of neurons to respond to a conditioned stimulus (CS) preceding an aversive unconditioned stimulus (US). The dorsolateral periacqueductal gray (dPAG) is a midbrain structure though to have an essential role in coordinating defensive behaviors in response to aversive stimulation. But its ability of dPAG neurons to encode a CS following fear conditioning as not been sufficiently studied.\n\nHere we used calcium imaging by fiber photometry to record the activity of dPAGVGluT2+ and dPAGGAD2+ neuronal populations during unconditioned and conditioned aversive stimulation. Then, following an unconditioned stimulation we performed a retrieval experiment to quantify memory-like responses of dPAG neurons. This shown that whilst both dPAGVGluT2+ and dPAGGAD2+ neuronal populations respond to direct US stimulation, and to CS stimulation during conditioning, only the dPAGVGluT2+ population persisted in responding to the CS stimulation during retrieval. Finally, to better understand dPAGVGluT2+ and dPAGGAD2+ connectivity patterns, we performed a cell specific monosynaptic retrograde rabies virus tracing experiment. This revealed that different patterns of fibers projects to dPAGVGluT2+ and dPAGGAD2+, further complementing our recording showing divergences between PAGVGluT2+ and dPAGGAD2+ populations.

neuroscience↗

bioRxiv2019

Interferon stimulated genes mark pathogenic cells of the emergency myelopoietic response to sterile tissue injury in mice and humans

Sterile tissue injury locally activates innate immune responses via interactions with damage associated molecular patterns (DAMPs). Here, by analyzing [~]120K single cell transcriptomes after myocardial infarction (MI) in mice and humans, we show neutrophil and monocyte subsets induce type I interferon (IFN) stimulated genes (ISGs) in myeloid progenitors of the bone marrow, far from the site of injury. In patients with acute MI, peripheral blood neutrophils and monocytes express ISGs at levels far beyond healthy individuals and comparable to patients with lupus. In the bone marrow of Tet2-/- mice, ISGs are spontaneously induced in myeloid progenitors and their progeny. In the heart, IFN responses are negatively regulated by Ccr2- resident macrophages in a Nrf2-dependent fashion. Our results show post-MI IFN signaling begins in the bone marrow, implicate multiple transcription factors in its regulation (Tet2, Irf3, Nrf2), and provide a clinical biomarker (ISG score) for studying post-MI IFN signaling in patients.

immunology↗

bioRxiv2019

Biosurfactant production maintains viability in anoxic conditions by depolarizing the membrane in Bacillus subtilis

The presence or absence of oxygen in the environment is a strong effector of cellular metabolism and physiology. Like many eukaryotes and some bacteria, Bacillus subtilis is an obligate aerobe that primarily utilizes oxygen during respiration to generate ATP. Despite the importance of oxygen for B. subtilis survival, we know little about how oxygen is consumed during growth and how populations respond to shifts in oxygen availability. Here, we find that when oxygen was depleted from stationary phase cultures [~]90% of B. subtilis 3610 cells died and lysed due to autolysin activity; the remaining cells maintained colony-forming ability. Interestingly, the domesticated 168 strain maintained a higher optical density than 3610 during oxygen depletion due to the formation of cell-wall-less protoplasts, but the remaining, rod-shaped cells were >100-fold less viable than 3610. We discovered that the higher viability in 3610 was due to its ability to produce the antibacterial compound surfactin, as surfactin addition rescued 168 viability and also increased yield in aerobic growth. We further demonstrate that surfactin strongly depolarizes the B. subtilis membrane, and that other known membrane-potential disruptors restore viability to 168. These findings highlight the importance of surfactin for survival during oxygen-depleted conditions and demonstrate that antimicrobials normally considered harmful can instead benefit cells in stressful conditions when the terminal electron acceptor in respiration is limiting.

microbiology↗