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Bacterial Growth and Division : Investigating Molecular Mechanisms Governing Cell Morphology in Streptomyces venezuelae

Massri, Dima LU orcid (2026)
Abstract
Bacteria shape their cells by coordinating the growth and division of their peptidoglycan cell wall. The filamentous Streptomyces species, renowned for their complex multicellular development, diverge from the rod-shaped model bacteria in their modes of growth and division, making them powerful models to study mechanisms behind morphogenesis. Instead of elongating at the sidewalls and simply dividing into two daughters, vegetatively growing streptomycetes employ two cellular processes to obtain and sculpt a vegetative mycelium of an inherently multicellular nature: a polarized mode of growth to extend hyphal tips and make branches and a unique type of cell division that does not involve cell separation. During sporulation, synchronized... (More)
Bacteria shape their cells by coordinating the growth and division of their peptidoglycan cell wall. The filamentous Streptomyces species, renowned for their complex multicellular development, diverge from the rod-shaped model bacteria in their modes of growth and division, making them powerful models to study mechanisms behind morphogenesis. Instead of elongating at the sidewalls and simply dividing into two daughters, vegetatively growing streptomycetes employ two cellular processes to obtain and sculpt a vegetative mycelium of an inherently multicellular nature: a polarized mode of growth to extend hyphal tips and make branches and a unique type of cell division that does not involve cell separation. During sporulation, synchronized cell division events produce spores. Throughout this life cycle, polar growth and cell division act as an integrated morphogenetic system, enabling development and morphological plasticity. This thesis investigates the two key molecular apparatuses underlying morphogenesis: the DivIVA-based polarisome and FtsZ-based divisome, using Streptomyces venezuelae as a model organism. The thesis work that pertains to polar growth describes a dual-operon system implicated in multicellular shape-organizing behaviors and polar growth-related mechanisms. In this work, we perform a systematic investigation of the eight Actinobacterial G protein systems (AGPSs) of S. venezuelae that are encoded by the conservons, a large family of operons that are conserved within Actinomycetota and exist in multiple copies in Streptomyces genomes. Our analysis primarily shows that AGPSs produced by conservons 1 and 2 are implicated in an apparent hyphal self-avoidance phenotype underlying the mycelial ordered architecture. Further characterization of individual components of conservons 1 and 2 demonstrates functional redundancy across their GTPase regulatory modules, each encoded collectively by cvnB, cvnC, and cvnD genes, and functional divergence of their ATPase sensory components, encoded by the cvnA genes, suggesting that this dual-operon system likely integrates operon-specific inputs into a shared GTPase core to regulate cell shape. We further establish a connection to polar growth by showing the enrichment of proteins encoded by these conservons at the hyphal tips, and an effect of the deletion of the two operons on DivIVA’s behavior and dynamics. Our work on cell division revisits the role of the ancient Gram-positive divisome member SepF and clarifies the functions of the two extra SepF paralogs, SepF2 and SepF3, that are uniquely encoded by Streptomyces genomes. Our work confirms the indispensability of the bona fide SepF for cell division and its role as a membrane anchor of the Z-ring. The study additionally uncovers non-essential yet important roles of SepF2 and SepF3 in cell division, with SepF3 being required for septum closure and the coordination between septum formation and chromosome segregation during sporulation, and both SepF2 and SepF3 having synergistic roles in facilitating cell division during vegetative growth. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor A. Elliot, Marie, Department of Biology, Hamilton, ON, Canada.
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Streptomyces, polar growth, polarisome, DivIVA, conservons, AGPS, cell division, SepF
pages
92 pages
publisher
Lund University, Faculty of Science, Department of Biology
defense location
Biologihörsalen (A213), Biologihuset, Sölvegatan 35, Lund
defense date
2026-09-11 09:00:00
ISBN
978-91-90202-65-4
978-91-90202-66-1
language
English
LU publication?
yes
id
62c5d7c4-c695-4060-bcb1-bfdc2c3c1159
date added to LUP
2026-08-17 10:27:09
date last changed
2026-08-19 03:27:04
@phdthesis{62c5d7c4-c695-4060-bcb1-bfdc2c3c1159,
  abstract     = {{Bacteria shape their cells by coordinating the growth and division of their peptidoglycan cell wall. The filamentous Streptomyces species, renowned for their complex multicellular development, diverge from the rod-shaped model bacteria in their modes of growth and division, making them powerful models to study mechanisms behind morphogenesis. Instead of elongating at the sidewalls and simply dividing into two daughters, vegetatively growing streptomycetes employ two cellular processes to obtain and sculpt a vegetative mycelium of an inherently multicellular nature: a polarized mode of growth to extend hyphal tips and make branches and a unique type of cell division that does not involve cell separation. During sporulation, synchronized cell division events produce spores. Throughout this life cycle, polar growth and cell division act as an integrated morphogenetic system, enabling development and morphological plasticity. This thesis investigates the two key molecular apparatuses underlying morphogenesis: the DivIVA-based polarisome and FtsZ-based divisome, using Streptomyces venezuelae as a model organism. The thesis work that pertains to polar growth describes a dual-operon system implicated in multicellular shape-organizing behaviors and polar growth-related mechanisms. In this work, we perform a systematic investigation of the eight Actinobacterial G protein systems (AGPSs) of S. venezuelae that are encoded by the conservons, a large family of operons that are conserved within Actinomycetota and exist in multiple copies in Streptomyces genomes. Our analysis primarily shows that AGPSs produced by conservons 1 and 2 are implicated in an apparent hyphal self-avoidance phenotype underlying the mycelial ordered architecture. Further characterization of individual components of conservons 1 and 2 demonstrates functional redundancy across their GTPase regulatory modules, each encoded collectively by cvnB, cvnC, and cvnD genes, and functional divergence of their ATPase sensory components, encoded by the cvnA genes, suggesting that this dual-operon system likely integrates operon-specific inputs into a shared GTPase core to regulate cell shape. We further establish a connection to polar growth by showing the enrichment of proteins encoded by these conservons at the hyphal tips, and an effect of the deletion of the two operons on DivIVA’s behavior and dynamics. Our work on cell division revisits the role of the ancient Gram-positive divisome member SepF and clarifies the functions of the two extra SepF paralogs, SepF2 and SepF3, that are uniquely encoded by Streptomyces genomes. Our work confirms the indispensability of the bona fide SepF for cell division and its role as a membrane anchor of the Z-ring. The study additionally uncovers non-essential yet important roles of SepF2 and SepF3 in cell division, with SepF3 being required for septum closure and the coordination between septum formation and chromosome segregation during sporulation, and both SepF2 and SepF3 having synergistic roles in facilitating cell division during vegetative growth.}},
  author       = {{Massri, Dima}},
  isbn         = {{978-91-90202-65-4}},
  keywords     = {{Streptomyces; polar growth; polarisome; DivIVA; conservons; AGPS; cell division; SepF}},
  language     = {{eng}},
  publisher    = {{Lund University, Faculty of Science, Department of Biology}},
  school       = {{Lund University}},
  title        = {{Bacterial Growth and Division : Investigating Molecular Mechanisms Governing Cell Morphology in Streptomyces venezuelae}},
  url          = {{https://lup.lub.lu.se/search/files/258247712/e-nailing_ex_Dima.pdf}},
  year         = {{2026}},
}