Understanding Type VII secretion in bacteria

Posted on March 22, 2021   by Kieran Bowran

In this blog, Kieran Bowran, first year PhD student at Newcastle University discusses his research into the system which allows bacteria to export proteins. Kieran has recently published an article on the type VII secretion system in the journal Microbiology.  

I am currently a first year PhD student in the Microbes in Health and Disease theme at Newcastle University, looking at type VII secretion systems (T7SS) in Gram-positive bacteria such as Staphylococcus aureus. Both my undergraduate and master’s degrees have been in microbiology, with a more recent focus on molecular microbiology. I initially joined Professor Palmer’s lab to undertake a master’s research project. This project was supposed to be laboratory based, but the COVID-19 pandemic struck right at the start of experiments, which meant that the project needed to be changed at the last minute! Luckily, it turned out to be a very fruitful change of direction. 

Some Gram-positive bacteria use their T7SSs to export toxic proteins into the surrounding environment, giving them a competitive growth advantage over nearby rival cells, which are more sensitive to these proteins. The ability of bacteria, to shape their microbial niche for their own benefit, is the aspect of research I find most interesting. Understanding how these community interactions influence bacterial populations could provide further insights into how human microbiomes develop. 

Prior observations in the Palmer lab had suggested that there was genetic diversity in the T7SS of Listeria monocytogenes, which I decided to probe further. Fortunately, a very useful bioinformatic tool, FlaGs, had just been described by Saha and colleagues. FlaGs analyses the conservation of genes around a gene of interest, allowing for localised comparisons across a wide number of genomes. As L. monocytogenes is an important opportunistic pathogen, hundreds of genome sequences were available to facilitate my analysis.  

Using FlaGs, I identified seven genetic variants of the essC gene, which I termed essC1 – essC7. EssC is a component of T7SS that powers the secretion process, and also recognises substrates. The EssC sequence variation was centred on the final two ATPase domains of EssC, and immediately downstream of each essC variant was a specific subset of predicted toxin and immunity genes.  

Across the genome sequences, I was able to identify 40 different toxins. Each of these toxins had an LXG domain at their N-terminus, which has also been found in Staphylococcus aureus and other bacteria in the firmicutes phylum. These toxins were encoded at specific, fixed positions on the L. monocytogenes chromosome, and always co-occurred with a gene for a probable immunity protein. On average, each strain encoded approximately four of these toxins, but they also often encoded immunity genes for toxins present in other strains. This is a clear sign that L. monocytogenes strains use their T7 toxins to inhibit the growth of other Listeria. 

Even in the same species, T7SS substrates are diverse. Our findings suggest that the T7SS and its toxin substrates are involved in more complex interactions than previously thought, which is reflected in the number of substrate proteins we identified. The presence of unrelated immunity genes suggests that certain strains have built up an ‘armoury’, to protect against antagonistic action by competing bacteria.  

Hopefully this research highlights the important role that antibacterial proteins secreted by the T7SS have in the dynamics of microbial communities. Further understanding of how these protein toxins interact with their structural target could aid the development of new antibiotics that target specific bacteria, relieving some of the pressure of current antibiotics.  

Read Kieran's reseach article 'Extreme genetic diversity in the type VII secretion system of Listeria monocytogenes suggests a role in bacterial antagonism' in Microbiology.