About

Dr. Mitchell Singer is the Principal Investigator of the Singer Lab at UC Davis. His research focuses on the biology of Myxobacteria, particularly investigating the roles of cyclase genes and defensin-like peptides in the development and behavior of Myxococcus xanthus. His work involves understanding the molecular mechanisms underlying fruiting body formation and bacterial development, contributing to the broader understanding of microbial social behaviors and signaling pathways.

Research topics

• Biology
• Cell biology
• Genetics
• Biochemistry
• Evolutionary biology
• Biophysics
• Computational biology
• Chemistry
• Microbiology

Selected publications

• Milestones in the development of Myxococcus xanthus as a model multicellular bacterium

  Publications of the UdS (Saarland University) · 2025-01-01

  otherOpen access

  From the humblest of beginnings (i.e. a pile of dry cow dung) over 80 years ago, the Gram-negative bacterium Myxococcus xanthus has emerged as a premier model system for studying diverse fields of bacteriology, including multicellular development, sporulation, motility, cell-envelope biogenesis, spatiotemporal regulation, signaling, photoreception, kin recognition, social evolution, and predation. As the flagship representative of myxobacteria found in varied terrestrial and aquatic environ ments, M. xanthus research has evolved into a collaborative global effort, as reflected by the contributions to this article. In celebration of the upcoming 50th anniversary of the International Conference on the Biology of Myxobacteria, this review highlights the historical and ongoing contributions of M. xanthus as a multifaceted model bacterium.

  PublisherDOI

• Milestones in the development of <i>Myxococcus xanthus</i> as a model multicellular bacterium

  Journal of Bacteriology · 2025-06-17 · 19 citations

  reviewOpen access

  ABSTRACT From the humblest of beginnings (i.e. a pile of dry cow dung) over 80 years ago, the Gram-negative bacterium Myxococcus xanthus has emerged as a premier model system for studying diverse fields of bacteriology, including multicellular development, sporulation, motility, cell-envelope biogenesis, spatiotemporal regulation, signaling, photoreception, kin recognition, social evolution, and predation. As the flagship representative of myxobacteria found in varied terrestrial and aquatic environments, M. xanthus research has evolved into a collaborative global effort, as reflected by the contributions to this article. In celebration of the upcoming 50th anniversary of the International Conference on the Biology of Myxobacteria, this review highlights the historical and ongoing contributions of M. xanthus as a multifaceted model bacterium.

  PublisherDOI

• Photomorphogenesis of Myxococcus macrosporus: new insights for light-regulation of cell development

  Photochemical & Photobiological Sciences · 2024-09-19 · 5 citations

  articleOpen access

  Myxobacteria are non-photosynthetic bacteria distinguished among prokaryotes by a multicellular stage in their life cycle known as fruiting bodies that are formed in response to nutrient deprivation and stimulated by light. Here, we report an entrained, rhythmic pattern of Myxococcus macrosporus fruiting bodies, forming consistently spaced concentric rings when grown in the dark. Light exposure disrupts this rhythmic phenotype, resulting in a sporadic arrangement and reduced fruiting-body count. M. macrosporus genome encodes a red-light photoreceptor, a bacteriophytochrome (BphP), previously shown to affect the fruiting-body formation in the related myxobacterium Stigmatella aurantiaca. Similarly, the formation of M. macrosporus fruiting bodies is also impacted by the exposure to BphP-specific wavelengths of light. RNA-Seq analysis of M. macrosporus revealed constitutive expression of the bphP gene. Phytochromes, as light-regulated enzymes, control many aspects of plant development including photomorphogenesis. They are intrinsically correlated to circadian clock proteins, impacting the overall light-mediated entrainment of the circadian clock. However, this functional relationship remains unexplored in non-photosynthetic prokaryotes. Genomic analysis unveiled the presence of multiple homologs of cyanobacterial core oscillatory gene, kaiC, in various myxobacteria, including M. macrosporus, S. aurantiaca and M. xanthus. RNA-Seq analysis verified the expression of all kaiC homologs in M. macrosporus and the closely related M. xanthus, which lacks bphP genes. Overall, this study unravels the rhythmic growth pattern during M. macrosporus development, governed by environmental factors such as light and nutrients. In addition, myxobacteria may have a time-measuring mechanism resembling the cyanobacterial circadian clock that links the photoreceptor (BphP) function to the observed rhythmic behavior.

  PublisherOA PDFDOI

• CglB adhesins secreted at bacterial focal adhesions mediate gliding motility

  bioRxiv (Cold Spring Harbor Laboratory) · 2020 · 7 citations

  • Cell biology
  • Biology
  • Biophysics

  A bstract The predatory deltaproteobacterium Myxococcus xanthus uses a helically-trafficked motor at bacterial focal adhesion (bFA) sites to power gliding motility. Using TIRF and force microscopy, we herein identify the integrin αI-domain-like outer-membrane (OM) lipoprotein CglB as an essential substratum-coupling protein of the gliding motility complex. Similar to most known OM lipoproteins, CglB is anchored on the periplasmic side of the OM and thus a mechanism must exist to secrete it to the cell surface in order for it to interact with the underlying substratum. We reveal this process to be mediated by a predicted OM β-barrel structure of the gliding complex. This OM platform was found to regulate the conformational activation and secretion of CglB across the OM. These data suggest that the gliding complex promotes surface exposure of CglB at bFAs, thus explaining the manner by which forces exerted by inner-membrane motors are transduced across the cell envelope to the substratum; they also uncover a novel protein secretion mechanism, highlighting the ubiquitous connection between secretion and bacterial motility.

  PublisherOA PDFDOI

• Modulation of bacterial multicellularity via spatio-specific polysaccharide secretion

  PLoS Biology · 2020 · 55 citations

  • Biology
  • Cell biology
  • Microbiology

  The development of multicellularity is a key evolutionary transition allowing for differentiation of physiological functions across a cell population that confers survival benefits; among unicellular bacteria, this can lead to complex developmental behaviors and the formation of higher-order community structures. Herein, we demonstrate that in the social δ-proteobacterium Myxococcus xanthus, the secretion of a novel biosurfactant polysaccharide (BPS) is spatially modulated within communities, mediating swarm migration as well as the formation of multicellular swarm biofilms and fruiting bodies. BPS is a type IV pilus (T4P)-inhibited acidic polymer built of randomly acetylated β-linked tetrasaccharide repeats. Both BPS and exopolysaccharide (EPS) are produced by dedicated Wzx/Wzy-dependent polysaccharide-assembly pathways distinct from that responsible for spore-coat assembly. While EPS is preferentially produced at the lower-density swarm periphery, BPS production is favored in the higher-density swarm interior; this is consistent with the former being known to stimulate T4P retraction needed for community expansion and a function for the latter in promoting initial cell dispersal. Together, these data reveal the central role of secreted polysaccharides in the intricate behaviors coordinating bacterial multicellularity.

  PublisherOA PDFDOI

• Modulation of bacterial multicellularity via spatiotemporal polysaccharide secretion

  bioRxiv (Cold Spring Harbor Laboratory) · 2020-02-20

  preprintOpen access

  A bstract The development of multicellularity is a key evolutionary transition allowing for differentiation of physiological functions across a cell population that confers survival benefits; among unicellular bacteria, this can lead to complex developmental behaviours and the formation of higher-order community structures. Herein, we demonstrate that in the social δ-proteobacterium Myxococcus xanthus , the secretion of a novel secreted biosurfactant polysaccharide (BPS) is temporally and spatially modulated within communities, mediating swarm migration as well as the formation of multicellular swarm biofilms and fruiting bodies. BPS is a type IV pilus-inhibited acidic polymer built of randomly-acetylated β-linked tetrasaccharide repeats. Both BPS and the “shared good” EPS are produced by dedicated Wzx/Wzy-dependent polysaccharide assembly pathways distinct from that responsible for spore coat assembly. To our knowledge, such pathways have never-before been explicitly shown to synthesize a biosurfactant. Together, these data reveal the central role of secreted polysaccharides in the intricate behaviours coordinating bacterial multicellularity.

  PublisherOA PDFDOI

• Global gene expression analysis of the Myxococcus xanthus developmental time course

  Genomics · 2020 · 26 citations

  Senior authorCorresponding
  • Biology
  • Genetics
  • Computational biology

  To accurately identify the genes and pathways involved in the initiation of the Myxococcus xanthus multicellular developmental program, we have previously reported a method of growing vegetative populations as biofilms within a controllable environment. Using a modified approach to remove up to ~90% rRNAs, we report a comprehensive transcriptional analysis of the M. xanthus developmental cycle while comparing it with the vegetative biofilms grown in rich and poor nutrients. This study identified 1522 differentially regulated genes distributed within eight clusters during development. It also provided a comprehensive overview of genes expressed during a nutrient-stress response, specific development time points, and during development initiation and regulation. We identified several differentially expressed genes involved in key central metabolic pathways suggesting their role in regulating myxobacterial development. Overall, this study will prove an important resource for myxobacterial researchers to delineate the regulatory and functional pathways responsible for development from those of the general nutrient stress response.

  PublisherDOI

• Bacterial interactions in the female genital tract: A triangle affair between pathogens, microbiota, and host

  Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) · 2019-01-18

  dissertationOpen access1st authorCorresponding
  Publisher

• Peripheral rods: a specialized developmental cell type in Myxococcus xanthus

  Genomics · 2019-10-09 · 17 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Diversity and Evolution of Myxobacterial Type IV Pilus Systems

  Frontiers in Microbiology · 2018-07-19 · 12 citations

  articleOpen accessSenior authorCorresponding

  Type IV pili (T4P) are surface-exposed protein fibers that play key roles in the bacterial life cycle via surface attachment/adhesion, biofilm formation, motility, and development. The order Myxococcales (myxobacteria) are members of the class Deltaproteobacteria and known for their large genome size and complex social behaviors, including gliding motility, fruiting body formation, biofilm production, and prey hunting. Myxococcus xanthus, the best-characterized member of the order, relies on the appropriate expression of 17 type IVa (T4aP) genes organized in a single cluster plus additional genes (distributed throughout the genome) for social motility and development. Here, we compared T4aP genes organization within the myxobacteria to understand their evolutionary origins and diversity. We found that T4aP genes are organized as large clusters in suborder Cystobacterineae, whereas in other two suborders Sorangiineae and Nannocystineae, these genes are dispersed throughout the genome. Based on the genomic organization, the phylogeny of conserved proteins, and synteny studies among 28 myxobacterial and 66 Proteobacterial genomes, we propose an evolutionary model for the origin of myxobacterial T4aP genes independently from other orders in class Deltaproteobacteria. Considering a major role for T4P, this study further proposes the origins and evolution of social motility in myxobacteria and provides a foundation for understanding how complex-behavioral traits, such as gliding motility, multicellular development, etc. might have evolved in this diverse group of complex organisms.

  PublisherDOI

Recent grants

• NIH Grant R01GM054592

  NIH · $982k · 2009

• DNA replication a checkpoint in regulating development in Myxococcus xanthus

  NSF · $840k · 2014–2018

• Transcriptional Control of Early Development in Myxococcus Xanthus

  NSF · $584k · 2010–2015

• NIH Grant R29GM054592

  NIH · $540k · 2003

Frequent coauthors

• G. Hochschild

  162 shared

• William A. Massey

  Princeton University

  130 shared

• E. Singer

  81 shared

• Elizabeth M. Pierce

  Wake Forest University

  81 shared

• Allen H. Spanier

  Jewish General Hospital

  81 shared

• Arthur Doob

  IBM (United States)

  81 shared

• John G. Gleason

  École Polytechnique Fédérale de Lausanne

  81 shared

• Binod B. De

  Fujifilm (United States)

  81 shared

Labs

• Singer LabPI