Hanna Eriksson: Cut-throat Competitors and Collaborative Companions: Investigating the varied consequences of delivered contact-dependent inhibition effectors.

Abstract

As opposed to in a laboratory setting, microorganisms in the wild must compete with other organisms for nutrients and space to survive and grow. To “win” this competition, bacteria can maximize their own fitness by clever adaptations to the niche, but they can also reduce the fitness of their opponents by delivering toxic molecules. The focus of this thesis, Contact-Dependent growth Inhibition (CDI), represents one way in which toxins can be delivered.

To date, many aspects of CDI have been studied, but much still remains to be explored. 

The delivery mechanism has been greatly elucidated, revealing e.g. that delivery to kin-cells is possible, sometimes preferred, and can be associated with persister formation. However, how kin-delivery leads to persister formation remains unknown. Similarly, while myriad different toxins have been identified, many remain uncharacterized and thus we cannot yet estimate the scope of possible effects on either non-immune or kin-cells. Finally, bacteria sometimes carry multiple CDI systems, but neither how frequently this occurs nor what benefits this could confer is known. This thesis includes four manuscripts (I-IV) which explore some of these mysteries. 

In manuscript I, we found that kin-delivery of the DNA-damaging effector CdiA-CTo11 leads to heterogeneous induction of the DNA-damage response. We further determine that this heterogeneity occurs through excessive delivery to, rather than insufficient immunity in, the cells that become induced.  

In manuscript II, we determined that CDI systems with narrow delivery spectrum are relatively rare and that they are often found together with broader-range systems. We also found that synergistic effects between toxins are rare, but that carrying multiple systems can be relevant to limit the risk of target resistance development. 

In manuscript III we characterized a new toxin, CdiA-CTR12 and found that it utilizes the import protein MetNI and that it affects genes involved in sulfate assimilation, representing a new effect of CdiA-CT delivery. 

Finally, in manuscript IV we found that intoxication dynamics, induced target-genes and kin-delivery effects all vary greatly even between toxins with the same reported activity. 

Together, these manuscripts illustrate the variability in effects of CdiA delivery to both competitors and kin.