Using zebrafish to characterise the immune system response to interbacterial competition
Bacteria growing in large multispecies populations are in constant competition with each other as they fight for resources. Amidst this struggle, many bacteria have evolved specialized systems to directly intoxicate and destroy other bacteria. This 'bacterial warfare' has been demonstrated to be one of the primary drivers of bacterial population dynamics, particularly in bacterial communities present inside animal hosts (i.e. the microbiome).
Full caption description: (Left) Illustration of zebrafish larvae indicating the site of bacterial injection and downstream analysis workflow, which included measuring bacterial growth, measuring host immune responses (cytokines), and assessing the health of the zebrafish. (Right) Health requires a balanced immune response: too little enables uncontrolled pathogen growth, but too much results in host cellular damage. T6SS-mediated bacterial killing by different bacterial species impacts different parts of this scale. On one end, T6SS-induced inflammation sensitizes the host to less inherently pathogenic bacteria like Acinetobacter baylyi, while on the other, suppression of inflammation by corticosteroids like dexamethasone allows overt pathogens like Vibrio cholerae to grow uncontrolled. T6SS-mediated killing by V. cholerae exists in a unique place where the heightened inflammatory response it induces counterintuitively also enables it to grow unchecked.
Interbacterial competition plays an important role in the dynamics of bacterial communities as individual species compete for nutrients and space. However, this 'bacterial warfare' does not occur in a vacuum. Animal hosts that house such bacterial communities naturally also interact with them and manage the fallout of their competition. Notably, bacterial cell components are known to be highly immunogenic.
In this work, Dr Ho's team used a zebrafish model to investigate the nature of host responses to distinct forms of interbacterial antagonism. Specifically, they looked at bacterial killing mediated by the type VI secretion system (T6SS) as well as killing mediated by secreted antibacterial toxins, called bacteriocins.
Dr Brian Ho commented: "We observed an inverse relationship between the efficiency of the bacterial killing and the severity and duration of the host inflammatory response. In other words, better bacterial killing leads to less host immune response."
So why then do pathogens maintain these less efficient killing mechanisms? The team's observations of the pathogen Vibrio cholerae, the causative agent of the diarrheal disease cholerae, might be the answer. As it turns out, V. cholerae can take advantage of the elevated immune response caused by inefficient interbacterial competition to enhance its growth inside the host. In other words, this pathogen can use its antibacterial system not as a means of eliminating competitors, but rather as a way of controlling the host environment to its own ends.
Further Information
Research in the School of Natural Sciences
Study Biological Sciences at Birkbeck