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Microbial Life Finds a Way; Exploring protein function, interactions, modularity, and evolution through bioinformatics

Nakamoto, Jose LU orcid (2026) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
Horizontal gene transfer (HGT) is a central driver of bacterial evolution that utilises mobile genetic elements (MGEs) to enable the rapid acquisition and dissemination of genetic traits across microbial populations. Among these traits, defence systems against bacteriophages play a critical role in shaping host-parasite interactions and microbial community dynamics. Toxin-antitoxin (TA) systems, originally described as plasmid maintenance modules, are now recognised as major components of bacterial immunity. These systems are highly diverse, widely distributed across bacterial genomes, and frequently associated with MGEs, highlighting their mobility and evolutionary plasticity. A defining feature of TA systems is their modularity, with... (More)
Horizontal gene transfer (HGT) is a central driver of bacterial evolution that utilises mobile genetic elements (MGEs) to enable the rapid acquisition and dissemination of genetic traits across microbial populations. Among these traits, defence systems against bacteriophages play a critical role in shaping host-parasite interactions and microbial community dynamics. Toxin-antitoxin (TA) systems, originally described as plasmid maintenance modules, are now recognised as major components of bacterial immunity. These systems are highly diverse, widely distributed across bacterial genomes, and frequently associated with MGEs, highlighting their mobility and evolutionary plasticity. A defining feature of TA systems is their modularity, with toxins and antitoxins belonging to multiple protein families that can be recombined to generate novel functional systems. Furthermore, a subset of these modules incorporates a SecB-like chaperone, forming toxin-antitoxin-chaperone (TAC) systems that add an additional regulatory layer. Despite extensive availability of genomic data, many of these systems remain uncharacterised due to limitations in sequence-based annotation, underscoring the importance of integrating structural and comparative approaches to explore the protein universe.
In this thesis, three complementary studies were conducted. The annotation of a global TA network revealed extensive modularity and functional connections to defence systems. A large-scale survey of SecB homologues expanded TAC diversity into eight classes, showing structural conservation despite sequence divergence. Finally, analysis of P1-like phage-plasmids identified a hypervariable hotspot enriched in putative defence systems, highlighting MGEs as reservoirs of immune innovation.
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Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Senior Team Leader Bateman, Alex, EMBL's European Bioinformatics Institute, Cambridge, United Kingdom
organization
publishing date
type
Thesis
publication status
published
subject
keywords
MGEs, TA, TAC, Phage-defence, Antiphage immunity
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2026:97
pages
79 pages
publisher
Lund University, Faculty of Medicine
defense location
Belfragesalen, BMC D15, Klinikgatan 32 i Lund
defense date
2026-06-18 13:00:00
ISSN
1652-8220
ISBN
978-91-8021-895-5
language
English
LU publication?
yes
id
ddc47bd4-5fe5-4ced-99be-a73e463afd60
date added to LUP
2026-05-20 10:21:22
date last changed
2026-05-21 13:39:25
@phdthesis{ddc47bd4-5fe5-4ced-99be-a73e463afd60,
  abstract     = {{Horizontal gene transfer (HGT) is a central driver of bacterial evolution that utilises mobile genetic elements (MGEs) to enable the rapid acquisition and dissemination of genetic traits across microbial populations. Among these traits, defence systems against bacteriophages play a critical role in shaping host-parasite interactions and microbial community dynamics. Toxin-antitoxin (TA) systems, originally described as plasmid maintenance modules, are now recognised as major components of bacterial immunity. These systems are highly diverse, widely distributed across bacterial genomes, and frequently associated with MGEs, highlighting their mobility and evolutionary plasticity. A defining feature of TA systems is their modularity, with toxins and antitoxins belonging to multiple protein families that can be recombined to generate novel functional systems. Furthermore, a subset of these modules incorporates a SecB-like chaperone, forming toxin-antitoxin-chaperone (TAC) systems that add an additional regulatory layer. Despite extensive availability of genomic data, many of these systems remain uncharacterised due to limitations in sequence-based annotation, underscoring the importance of integrating structural and comparative approaches to explore the protein universe.<br/>In this thesis, three complementary studies were conducted. The annotation of a global TA network revealed extensive modularity and functional connections to defence systems. A large-scale survey of SecB homologues expanded TAC diversity into eight classes, showing structural conservation despite sequence divergence. Finally, analysis of P1-like phage-plasmids identified a hypervariable hotspot enriched in putative defence systems, highlighting MGEs as reservoirs of immune innovation.<br/>}},
  author       = {{Nakamoto, Jose}},
  isbn         = {{978-91-8021-895-5}},
  issn         = {{1652-8220}},
  keywords     = {{MGEs; TA; TAC; Phage-defence; Antiphage immunity}},
  language     = {{eng}},
  number       = {{2026:97}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Microbial Life Finds a Way; Exploring protein function, interactions, modularity, and evolution through bioinformatics}},
  year         = {{2026}},
}