Biology subjects

Chai, Y.

Publications and source records attributed to Chai, Y..

At least 55 records · Page 3Linked to original sources

bioRxiv2023

The scale-invariant covariance spectrum of brain-wide activity

Understanding neural activity organization is vital for deciphering brain function. By recording whole-brain calcium activity in larval zebrafish during hunting and spontaneous behaviors, we find that the shape of the neural activity space, described by the neural covariance spectrum, is scale-invariant: a smaller, randomly sampled cell assembly resembles the entire brain. This phenomenon can be explained by Euclidean Random Matrix theory, where neurons are reorganized from anatomical to functional positions based on their correlations. Three factors contribute to the observed scale invariance: slow neural correlation decay, higher functional space dimension, and neural activity heterogeneity. In addition to matching data from zebrafish and mice, our theory and analysis demonstrate how the geometry of neural activity space evolves with population sizes and sampling methods, thus revealing an organizing principle of brain-wide activity.

neuroscience↗

bioRxiv2022

Carryover effects of tire wear particle leachate threats reproduction across multiple generations

Toxic additives leached from tire wear particle (TWP) have been linked to some collective death events of fish, also impose impacts on zooplankton as secondary consumer in aquatic food web. In addition to direct impacts of TWP leachate at the current generation, potential delayed carryover from past exposure across multi-generational lineage may augment impacts on individual reproduction, then population maintenance. We investigated the carryover effects from persistent exposure and past TWP leachate exposure along generation passaging on the individual reproduction of rotifer, Brachionus calyciflorus, a typical zooplankton. For rotifer treated with TWP leachate across continuous 7 generations, their offspring were divided into parental exposure or no exposure in each generation. And rotifer transferred into no exposure were maintained for 3 generations to eliminate indirect exposure through their parental germ. The similar response of reproduction, via carryover effects from parental exposure, also emerged in offspring without exposure. Persistent exposure across multiple generations additively impaired individual reproduction performance by transferring from its hermetic effects in original generation, even caused final population collapse. TWP leachate could impose cascading toxicity on population persistence of zooplankton via carryover and cumulative effects on reproduction for long term, which must be considered in risk assessment and management policy to alleviate the effects of TWP.

ecology↗

bioRxiv2022

Style Transfer Generative Adversarial Networks to Harmonize Multi-Site MRI to a Single Reference Image to Avoid Over-Correction

Recent work within neuroimaging consortia have aimed to identify reproducible, and often subtle, brain signatures of psychiatric or neurological conditions. To allow for high-powered brain imaging analyses, it is often necessary to pool MR images that were acquired with different protocols across multiple scanners. Current retrospective harmonization techniques have shown promise in removing cross-site image variation. However, most statistical approaches may over-correct for technical, scanning-related, variation as they cannot distinguish between confounded image-acquisition based variability and cross-site population variability. Such statistical methods often require that datasets contain subjects or patient groups with similar clinical or demographic information to isolate the acquisition-based variability. To overcome this limitation, we consider cross-site MRI image harmonization as a style transfer problem rather than a domain transfer problem. Using a fully unsupervised deep-learning framework based on a generative adversarial network (GAN), we show that MR images can be harmonized by inserting the style information encoded from a single reference image, without knowing their site/scanner labels a priori. We trained our model using data from five large-scale multi-site datasets with varied demographics. Results demonstrated that our style-encoding model can harmonize MR images, and match intensity profiles, without relying on traveling subjects. This model also avoids the need to control for clinical, diagnostic, or demographic information. We highlight the effectiveness of our method for clinical research by comparing extracted cortical and subcortical features, brain-age estimates, and case-control effect sizes before and after the harmonization. We showed that our harmonization removed the cross-site variances, while preserving the anatomical information and clinical meaningful patterns. We further demonstrated that with a diverse training set, our method successfully harmonized MR images collected from unseen scanners and protocols, suggesting a promising novel tool for ongoing collaborative studies. Source code is released in USC-IGC/style_transfer_harmonization (github.com).

neuroscience↗

bioRxiv2022

Canonical Wnt signaling regulates soft palate development through mediating ciliary homeostasis

Craniofacial morphogenesis requires complex interactions among tissues, signaling pathways, secreted factors, and organelles. The details of these interactions remain elusive. In this study, we analyzed the molecular mechanisms and homeostatic cellular activities governing soft palate development to improve regenerative strategies for cleft palate patients. We have identified canonical Wnt signaling as a key signaling pathway primarily active in cranial neural crest (CNC)-derived mesenchymal cells surrounding soft palatal myogenic cells. Using Osr2-Cre;{beta}-cateninfl/fl mice, we further discovered that Wnt signaling is indispensable for mesenchymal cell proliferation and subsequently myogenesis through mediating ciliogenesis. Specifically, we identified that Wnt signaling directly regulates expression of the ciliary gene Ttll3 through {beta}-catenin/Tcf7l2 complex. Impaired ciliary disassembly leads to differentiation defects of mesenchymal cells and indirectly disrupts myogenesis through decreased expression of Dlk1, a mesenchymal cell-derived pro-myogenesis factor. Moreover, we found that restoring ciliary homeostasis rescues mesenchymal cell proliferation in Osr2-Cre;{beta}-cateninfl/fl samples. This study highlights the role of Wnt signaling in palatogenesis through controlling ciliary homeostasis, which establishes a new mechanism for Wnt-regulated craniofacial morphogenesis.

developmental biology↗

bioRxiv2022

Layer-specific, retinotopically-diffuse modulation in human visual cortex by emotional faces

Emotionally expressive faces evoke enhanced neural responses in multiple brain regions, a phenomenon thought to depend critically on the amygdala. This emotion-related modulation is evident even in primary visual cortex (V1), providing a potential neural substrate by which emotionally salient stimuli can affect perception. How does emotional valence information, computed in the amygdala, reach V1? Here we use high-resolution functional MRI to investigate the layer profile and retinotopic distribution of neural activity specific to emotional facial expressions. Across three experiments, human participants viewed centrally presented face stimuli varying in emotional expression and performed a gender judgment task. We found that facial valence sensitivity was evident only in superficial cortical layers and was not restricted to the retinotopic location of the stimuli, consistent with diffuse feedback-like projections from the amygdala. Together, our results provide a feedback mechanism by which the amygdala directly modulates activity at the earliest stage of visual processing.

neuroscience↗

bioRxiv2022

De novo design of site-specific protein interactions with learned surface fingerprints

Physical interactions between proteins are essential for most biological processes governing life. However, the molecular determinants of such interactions have been challenging to understand, even as genomic, proteomic, and structural data grows. This knowledge gap has been a major obstacle for the comprehensive understanding of cellular protein-protein interaction (PPI) networks and for the de novo design of protein binders that are crucial for synthetic biology and translational applications. We exploit a geometric deep learning framework operating on protein surfaces that generates fingerprints to describe geometric and chemical features critical to drive PPIs. We hypothesized these fingerprints capture the key aspects of molecular recognition that represent a new paradigm in the computational design of novel protein interactions. As a proof-of-principle, we computationally designed several de novo protein binders to engage four protein targets: SARS-CoV-2 spike, PD-1, PD-L1, and CTLA-4. Several designs were experimentally optimized while others were purely generated in silico, reaching nanomolar affinity with structural and mutational characterization showing highly accurate predictions. Overall, our surface-centric approach captures the physical and chemical determinants of molecular recognition, enabling a novel approach for the de novo design of protein interactions and, more broadly, of artificial proteins with function.

bioengineering↗

bioRxiv2022

TGF-β signaling and Creb5 cooperatively regulate Fgf18 to control pharyngeal muscle development

The communication between myogenic cells and their surrounding connective tissues is indispensable for muscle morphogenesis. During late embryonic development in mice, myogenic progenitors migrate to discrete sites to form individual muscles. The detailed mechanism of this process remains unclear. Using levator veli palatini (LVP) development as a model, we systematically investigated how a distinct connective tissue subpopulation, perimysial fibroblasts, communcates with myogenic cells to regulate mouse pharyngeal myogenesis. Using single-cell RNAseq data analysis, we identified that TGF-{beta} signaling is a key regulator for the perimysial fibroblasts. Loss of TGF-{beta} signaling led to defects in perimysial fibroblasts and subsequently muscle formation in Osr2-Cre;Alk5fl/fl mice. In particular, a perimysial fibroblast-specific regulator, Creb5, interacts with TGF-{beta} signaling to enable specific activation of perimysial fibroblast-derived signals such as Fgf18. Moreover, Fgf18 supports pharyngeal muscle development in vivo and its exogenous expression can partially rescue myogenic cell numbers in Osr2-Cre;Alk5fl/fl samples, illustrating that TGF-{beta}-regulated Fgf18 signaling is required for LVP development. Collectively, our findings revealed the mechanism by which TGF-{beta} signaling achieves its specificity in defining the perimysial-to-myogenic signals for pharyngeal myogenesis.

developmental biology↗

bioRxiv2022

Spatiotemporal landscape of SARS-CoV-2 pulmonary infection reveals Slamf9+Spp1+ macrophages promoting viral clearance and inflammation resolution

While SARS-CoV-2 pathogenesis has been intensively investigated, the host mechanisms of viral clearance and inflammation resolution are still elusive because of the ethical limitation of human studies based on COVID-19 convalescents. Here we infected Syrian hamsters by authentic SARS-CoV-2 and built an ideal model to simulate the natural recovery process of SARS-CoV-2 infection from severe pneumonia1,2. We developed and applied a spatial transcriptomic sequencing technique with subcellular resolution and tissue-scale extensibility, i.e., Stereo-seq3, together with single-cell RNA sequencing (scRNA-seq), to the entire lung lobes of 45 hamsters and obtained an elaborate map of the pulmonary spatiotemporal changes from acute infection, severe pneumonia to the late viral clearance and inflammation resolution. While SARS-CoV-2 infection caused massive damages to the hamster lungs, including naive T cell infection and deaths related to lymphopenia, we identified a group of monocyte-derived proliferating Slamf9+Spp1+ macrophages, which were SARS-CoV-2 infection-inducible and cell death-resistant, recruiting neutrophils to clear viruses together. After viral clearance, the Slamf9+Spp1+ macrophages differentiated into Trem2+ and Fbp1+ macrophages, both responsible for inflammation resolution and replenishment of alveolar macrophages. The existence of this specific macrophage subpopulation and its descendants were validated by RNAscope in hamsters, immunofluorescence in hACE2 mice, and public human autopsy scRNA-seq data of COVID-19 patients. The spatiotemporal landscape of SARS-CoV-2 infection in hamster lungs and the identification of Slamf9+Spp1+ macrophages that is pivotal to viral clearance and inflammation resolution are important to better understand the critical molecular and cellular players of COVID-19 host defense and also develop potential interventions of COVID-19 immunopathology.

immunology↗

bioRxiv2022

Minor differences in peptide presentation between chicken MHC class I molecules can explain differences in disease susceptibility

The highly polymorphic classical major histocompatibility complexes (MHCs) can confer resistance or susceptibility to diseases. The chicken MHC is known to confer decisive resistance or susceptibility to various economically-important pathogens, including the iconic oncogenic herpesvirus that causes Mareks disease (MD). Only one classical class I gene, BF2, is expressed at a high level in chickens, so it was relatively easy to discern a hierarchy from well-expressed thermostable fastidious specialist alleles to promiscuous generalist alleles that are less stable and expressed less on the cell surface. The BF2*1901 is more highly expressed and more thermostable than the closely-related BF2*1501, but the data for peptide repertoire available did not obviously correlate as expected. Here, we confirm for newly-developed chicken lines that the chicken haplotype B15 confers resistance to MD compared to B19. Using gas phase sequencing of peptide pools, and using immunopeptidomics involving mass spectroscopy, we find that the BF2*1901 binds a greater variety of amino acids in some anchor positions than BF2*1501. However, by X-ray crystallography, we find that the peptide-binding groove of BF2*1901 is narrower and shallower. Though the self-peptides bound to BF2*1901 may appear more various than those of BF2*1501, the structures show that the wider and deeper peptide-binding groove of BF2*1501 allows it to tightly accept many more peptides overall, correlating with the expected hierarchies for expression level, thermostability and MD resistance. Moreover, the 2 helix of BF2*1901 is higher than BF2*1501, potentially reducing the number of T cell clones that can recognize this fastidious class I molecule. IMPORTANCEDisease susceptibility mechanism is complicated, but chicken infection of Mareks disease (MD) is one of ideal models, considering the only one highly expressed classical MHC class I, BF2. The different susceptibility of the two close alleles BF2*1901 and BF2*1501 with minor difference of expression and thermostability is still unfathomed. Here, we confirm B15 chicken confers resistance to MD compared to B19. But the BF2*1901 binds a broader variety of anchoring peptides than BF2*1501. This mystery was solved by the structural determination of the two molecules with one similar peptide. The wider and deeper peptide-binding groove of BF2*1501 allows it to tightly accept many more peptides overall, which is concordant to the expected hierarchies for expression level, thermostability and MD resistance.

immunology↗

bioRxiv2021

MS2 RNA aptamer enhances prime editing in rice

Prime editing is a universal and very promising precise genome editing technology. However, optimization of prime editor (PE) from different aspects remains vital for its use as a routine tool in plant basic research and crop molecular breeding. In this report, we tested MS2-based prime editor (MS2PE). We fused the M-MLV reverse transcriptase (RT) gene variant to the MS2 RNA binding protein gene, MCP, and allowed the MCP-RT fusion gene to co-express with the SpCas9 nickase gene, SpCas9H840A, and various engineered pegRNAs harboring MS2 RNA (MS2pegR). Compared with control PEs, MS2PEs significantly enhanced editing efficiency at four of six targets in rice protoplasts, and achieved 1.2[~]10.1-fold increase in editing efficiency at five of six targets in transgenic rice lines. Furthermore, we tested total 22 different MS2pegR scaffolds, 3 RT variants or genes, 2 MCP variants, and various combinations of the Cas9 nickase, RT, and MCP modules. Our results demonstrated an alternative strategy for enhancing prime editing.

molecular biology↗

bioRxiv2021

Kdm6b confers Tfdp1 with the competence to activate p53 signalling in regulating palatogenesis

Epigenetic regulation plays extensive roles in diseases and development. Disruption of epigenetic regulation not only increases the risk of cancer, but can also cause various developmental defects. However, it is still unclear how epigenetic regulators coordinate with tissue-specific regulatory factors during morphogenesis of specific organs. Using palatogenesis as a model, we reveal the functional significance of Kdm6b, a H3K27me3 demethylase, in regulating embryonic development. Our study shows that Kdm6b plays an essential role in neural crest development, and loss of Kdm6b disturbs p53 pathway-mediated activity, leading to complete cleft palate along with cell proliferation and differentiation defects. Furthermore, activity of H3K27me3 on the promoter of p53 is precisely controlled by Kdm6b, and Ezh2 in regulating p53 expression in cranial neural crest cells. More importantly, Kdm6b renders chromatin accessible to the transcription factor Tfdp1, which binds to the promoter of p53 along with Kdm6b to specifically activate p53 expression during palatogenesis. Collectively our results highlight the important role of the epigenetic regulator Kdm6b and how it cooperates with Tfdp1 to achieve its functional specificity in regulating p53 expression, and further provide mechanistic insights into the epigenetic regulatory network during organogenesis.

developmental biology↗

bioRxiv2021

Controllable drug release of pH-sensitive liposomes encapsulating artificial cytosol system

The fabrication of cell model containing artificial cytosol is challenging. Herein we constructed an artificial cytosol contained cell model by electroformation method. Agarose was selected as the main component of the artificial cytosol. Sucrose was added into agarose to regulate the sol viscosity and phase transition temperature (Tm). The viscosity of the sol with the mass ratio (agarose-sucrose) 1:9 was closest to the natural cytosolic. DSPC/20 mol% Chol was used to form large unilamellar vesicle (LUV) as cell model compartment. The rhodamine release experiment confirmed that the release of rhodamine from LUVs containing artificial cytosol took more time than that from LUVs containing pure water. The unique release profile makes agarose-sucrose@LUVs suitable as a drug carrier. Doxorubicin (DOX) is loaded in the agarose-sucrose@LUVs, and their half maximum inhibition concentration on HeLa cells is 0.015 mol L-1, which means 31.7 times increase in inhibition efficiency over free DOX.

biochemistry↗

bioRxiv2021

Style Transfer Using Generative Adversarial Networks for Multi-Site MRI Harmonization

Large data initiatives and high-powered brain imaging analyses require the pooling of MR images acquired across multiple scanners, often using different protocols. Prospective cross-site harmonization often involves the use of a phantom or traveling subjects. However, as more datasets are becoming publicly available, there is a growing need for retrospective harmonization, pooling data from sites not originally coordinated together. Several retrospective harmonization techniques have shown promise in removing cross-site image variation. However, most unsupervised methods cannot distinguish between image-acquisition based variability and cross-site population variability, so they require that datasets contain subjects or patient groups with similar clinical or demographic information. To overcome this limitation, we consider cross-site MRI image harmonization as a style transfer problem rather than a domain transfer problem. Using a fully unsupervised deep-learning framework based on a generative adversarial network (GAN), we show that MR images can be harmonized by inserting the style information encoded from a reference image directly, without knowing their site/scanner labels a priori. We trained our model using data from five large-scale multi-site datasets with varied demographics. Results demonstrated that our styleencoding model can harmonize MR images, and match intensity profiles, successfully, without relying on traveling subjects. This model also avoids the need to control for clinical, diagnostic, or demographic information. Moreover, we further demonstrated that if we included diverse enough images into the training set, our method successfully harmonized MR images collected from unseen scanners and protocols, suggesting a promising novel tool for ongoing collaborative studies.

neuroscience↗

bioRxiv2021

Embryonic requirements for Tcf12 in the development of the mouse coronal suture

A major feature of Saethre-Chotzen syndrome is coronal craniosynostosis, the fusion of the frontal and parietal bones at the coronal suture. It is caused by heterozygous loss-of-function mutations in the basic HLH transcription factors TWIST1 and TCF12. While compound heterozygous Tcf12; Twist1 mice display severe coronal synostosis, the individual role of Tcf12 has remained unexplored. Here we show that Tcf12 controls several key processes in calvarial development, including the rate of frontal and parietal bone growth, and the boundary between sutural and osteogenic cells. Genetic analysis supports an embryonic requirement for Tcf12 in suture formation, as combined deletion of Tcf12 in the embryonic neural crest and mesoderm, but not in the postnatal suture mesenchyme, disrupts the coronal suture. We also detect asymmetric distribution of Grem1 + mesenchymal cells on opposing sides of the wild-type frontal and parietal bones, which prefigures later bone overlap at the sutures. In Tcf12 mutants, reduced asymmetry correlates with lack of bone overlap. Our results indicate a largely embryonic function of Tcf12 in controlling the rate and asymmetrical growth of calvarial bones and establishment of suture boundaries, which together ensure the proper formation of the overlapping coronal suture.

developmental biology↗

bioRxiv2021

Bacterial galactosemia is caused by cytoplasmic interference of an essential cell wall biosynthesis glycosyltransferase

Bacterial galactosemia or "galactose death," triggered by incomplete galactose metabolism, was first discovered in Escherichia coli and Salmonella six decades ago, and later in many other microorganisms, yet the mechanism for the toxicity and subsequent cell death remains unclear. In Bacillus subtilis, galactosemia is manifested by a buildup of uridine-diphosphate-galactose (UDP-Gal) and a strong toxicity phenotype characterized by cell shape abnormality and rapid cell lysis. Here we present evidence that in B. subtilis, the toxicity is due to inhibition of cell wall biosynthesis through interference of the essential glycosyltransferase MurG that carries out lipid II synthesis from lipid I and uridine-diphosphate-N-acetyl-glucosamine (UDP-GlcNAc). Single-molecule imaging reveals real-time inhibition of cell wall biosynthesis and MurG activities in cells exhibiting toxicity. We further show that in vitro, MurG is able to utilize UDP-Gal as a substrate generating a "toxic" lipid II, causing a potential poisoning effect on peptidoglycan crosslinking. Evidence also suggests a similar mechanism in Vibrio cholerae and Staphylococcus aureus. Lastly, a strong synergistic lethality was seen in S. aureus wild-type cells treated with both galactose and sub-lethal doses of cell-wall antibiotics. Our study provides mechanistic explanation of the toxicity associated with bacterial galactosemia and its potential application in antibacterial solutions. SignificanceGalactosemia is a potentially fatal genetic disorder due to incomplete galactose metabolism, found in both eukaryotic and prokaryotic organisms. The molecular mechanisms of galactosemia-associated toxicity remain unclear in all cases. Here we present evidence that in the bacterium Bacillus subtilis, the toxicity is due to interference of an essential glycosyltransferase, MurG, which concerts lipid I to lipid II during peptidoglycan biosynthesis, by a nucleotide sugar derived from galactose metabolism. This interference leads to a halt of cell wall biosynthesis and structural defects causing rapid cell lysis. Our evidence also suggests a similar mechanism in other bacteria such as Staphylococcus aureus and Vibrio cholerae. Our study may help solve the long-time puzzle of bacterial galactosemia first uncovered six decades ago.

microbiology↗

bioRxiv2020

Insights into the diversity and survival strategies of soil bacterial isolates from the Atacama Desert

The Atacama Desert, the driest and oldest desert in the world, is a hostile environment for life. Despite the inhospitable conditions, bacterial sequences detected in this location suggest rich bacterial life. This study tested the idea that certain bacteria would thrive in this location and that some of them could be cultivated permitting further characterization. Environmental surface soil samples from 1-5 cm deep were collected from 18 diverse locations within the Atacama Desert. To assess the bacterial taxa, diversity, and abundance, Illumina 16S rRNA gene sequencing was performed directly on soil samples. Bacteria were also cultured from the samples. We have a collection of 74 unique bacterial isolates after cultivation and confirmation by 16S rRNA gene sequencing. Pigmentation, biofilm formation, antibiotic production against Escherichia coli MG1655 and Staphylococcus aureus HG003, and antibiotic resistance were assessed on these isolates. We found that approximately a third of the colonies produced pigments, 80% of isolates formed biofilms, many isolates had antibiotic activity against E. coli and/or S. aureus, and many were resistant to commercial antibiotics. The functional characterization of these isolates gives us insight into the adaptive bacterial strategies in harsh environments and enables us to learn about their possible use in agriculture, healthcare, or biotechnology. Originality-Significant StatementThis study provides the first microbial diversity analysis from Atacama Desert soil, presents the cultivation and isolation of 74 unique bacterial isolates, many of which may be novel genera and species, and explores pigment production, antibiotic production and resistance, and unique biofilm development as bacterial survival strategies for living within extreme environments.

microbiology↗

bioRxiv2020

Hericerin derivatives from Hericium erinaceus exert BDNF-like neurotrophic activity in central hippocampal neurons and enhance memory

The traditional medicinal mushroom Hericium erinaceus has long been known for enhancing the peripheral nerve regeneration through targeting nerve growth factor (NGF) neurotrophic activity. It was also reported to protect against ageing-dependent cognitive decline in wildtype and in Alzheimers disease mouse models suggesting a yet to be defined action on neurons of the central nervous system. Here, we purified and identified biologically active compounds from H. erinaceus, based on their ability to promote neurite outgrowth in hippocampal neurons. N-de phenylethyl isohericerin (NDPIH), an isoindoline compound from this mushroom together with its hydrophobic derivative hericene A, were highly potent in inducing extensive axon outgrowth and neurite branching in the absence of serum demonstrating high neurotropic activity. NDPIH also induced enlarged growth cones suggestive of a brain-derived neurotrophic factor (BDNF)-like activity. Pharmacological inhibition of tropomyosin receptor kinase B (TrkB) by ANA12 prevented NDPIH-induced neurotrophic activity providing evidence that NDPIH acts via TrkB receptors to mediate its neurotrophic effect in central neurons. Finally, in vivo treatment with H. erinaceus crude extract and hericene A significantly increased BDNF and downstream pathway and enhanced learning and memory in the novel object recognition memory test. Our results suggest that hericene A can promote BDNF-like activity in neurons in vitro and in vivo thereby enhancing recognition memory.

neuroscience↗

bioRxiv2020

Negative interplay between biofilm formation and competence in the environmental strains of Bacillus subtilis

Environmental strains of the soil bacterium Bacillus subtilis have valuable applications in agriculture, industry, and biotechnology. They are capable of forming robust biofilms and demonstrate excellent biological control activities in plant protection. However, environmental strains are genetically less accessible, a sharp contrast to the laboratory strains well known for their natural competence and a limitation toward their application. In this study, we observed that robust biofilm formation of the environmental strains greatly reduces the rate of competent cells within the biofilm. By using the model strain 3610, we reveal a cross-pathway regulation that allows biofilm matrix producers and competence-developing cells to undergo mutually exclusive cell differentiation. We show that the competence activator ComK represses the key biofilm regulatory gene sinI by directly binding to the sinI promoter, thus blocking competent cells from simultaneously becoming matrix producers. In parallel, the biofilm activator SlrR represses competence through three distinct mechanisms, involving both genetic regulation and cell morphological changes. We discuss potential implications of limiting competence in a bacterial biofilm. ImportanceThe soil bacterium Bacillus subtilis is capable of forming robust biofilms, a multicellular community important for its survival in the environment. B. subtilis also exhibits natural competence, the ability of cells to acquire genetic materials directly from the environment. By investigating competence development in situ during B. subtilis biofilm formation, we reveal that robust biofilm formation, an important feature of the environmental strains of B. subtilis, often greatly reduces the rate of competent cells within the biofilm. We characterize a cross-pathway regulation that allows cells associated with these two developmental events to undergo mutually exclusive cell differentiation during biofilm formation. Finally, we discuss potential biological implications of limiting competence in a bacterial biofilm.

microbiology↗