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How do orphan CdiA toxin modules affect the growth of bacteria and population heterogeneity?

Komi, Margarita (2022) MOBN03 20212
Degree Projects in Molecular Biology
Popular Abstract
Am I selfish? - Toxin edition

Many bacteria encode for toxin-antitoxin (TA) pairs. The toxin is a stable protein that targets essential bacterial components. The antitoxin is an easily-degraded antidote that protects cells from poisoning themselves. If cells lose the TA genes, they cannot produce more of either toxin or antitoxin. The unstable antitoxin is degraded fast, and the stable toxin is now free to act, poisoning cells that lose them. This ensures that only cells with the TA pair survive. Quite selfish genes, are they not?

Some of these pairs are part of bacterial delivery systems to other cells and are used as means of biological warfare, while others are independently expressed in each bacterium. One of these delivery... (More)
Am I selfish? - Toxin edition

Many bacteria encode for toxin-antitoxin (TA) pairs. The toxin is a stable protein that targets essential bacterial components. The antitoxin is an easily-degraded antidote that protects cells from poisoning themselves. If cells lose the TA genes, they cannot produce more of either toxin or antitoxin. The unstable antitoxin is degraded fast, and the stable toxin is now free to act, poisoning cells that lose them. This ensures that only cells with the TA pair survive. Quite selfish genes, are they not?

Some of these pairs are part of bacterial delivery systems to other cells and are used as means of biological warfare, while others are independently expressed in each bacterium. One of these delivery systems, called Contact-Dependent growth Inhibition (CDI) can do both. In the genetic CDI region there are toxins that can be delivered to target bacterial cells through cell-cell contact. Delivery between two genetically identical cells has been connected to increased survival of bacteria after antibiotic treatment. After the main CDI region, many bacteria possess an array of up to 11 pairs, called orphan CDI toxin-antitoxin pairs, which however do not get delivered. Both the delivered and at least one orphan CDI pair were found to produce functional toxins and antitoxins that they do not deliver, a phenomenon we call internal expression. New data suggest that internal expression can also lead to an increase in survival after antibiotic treatment.

Do orphan CDI toxins actually cause this increase? Under which conditions are they expressed and how is this expression controlled? Does internal expression of these toxins affect the cells in any way or are they just selfish genes that do everything they can to stay in bacterial DNA? To answer the above questions, we performed stress, antibiotic survival and biofilm tests using bacteria that express two orphan pairs. Our results indicate that this increase in antibiotic survival associated with internal expression is not always there when bacteria grow without stress. However, there is an increase in expression of the pairs when bacteria are stressed because of lack of nutrients. Still, this increase does not affect the growth of bacteria or their survival after antibiotic treatment. Does that mean that orphan CDI toxins are indeed just selfish? It is a bit more complicated than that. In a natural pathogenic bacterium we tested, an increase in survival was seen when cells were stressed by acids they usually encounter in the gut. Further investigations will reveal the true self of orphan CDI toxins.

Master’s Degree Project in Molecular Biology, 60 credits, 2022
Department of Biology, Lund University

Advisor: Sanna Koskiniemi,
Department of Cell and Molecular biology, Uppsala University (Less)
Please use this url to cite or link to this publication:
author
Komi, Margarita
supervisor
organization
course
MOBN03 20212
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9103281
date added to LUP
2022-11-17 10:40:39
date last changed
2022-11-17 10:40:39
@misc{9103281,
  author       = {{Komi, Margarita}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{How do orphan CdiA toxin modules affect the growth of bacteria and population heterogeneity?}},
  year         = {{2022}},
}