Fleming showcase presentations: your questions answered

Posted on January 22, 2021   by Microbiology Society

In November 2020, the Microbiology Society held a one-week digital event series to celebrate the impact of microbiologists’ past, present and future. The event, called ‘Why Microbiologists Matter,’ included a two-day Fleming Showcase in celebration of the Society’s 75th Anniversary. The showcase included a series of guest lectures from outstanding microbiologists and five-minute thesis presentations from early career microbiologists. Here, the speakers answer some of the questions submitted after their talks. 

Professor Bonnie Bassler: Quorum-sensing communication: from viruses to bacteria to eukaryotes 

Have you tried the pure DPO on any other species' biofilms at all, in case they use a different receptor? 

Yes indeed, that is our current experiment.  

I don't understand how the controllable phage [work] 

The engineered phages have promoters upstream of the q gene that are responsive to the input the user decides. Thus, the phages will launch the lysis program exclusively in response to a cue the scientist decides/supplies. 

Do bacterial sRNAs tend to act in isolation or can they act in tandem with other sRNAs/regulatory RNAs in a larger network, more akin to miRNAs in eukaryotic cells? 

Yes indeed. Small RNAs commonly act redundantly. There is a huge and fascinating field concerned with bacterial small RNAs. They are amazing regulatory devices. 

With the assay you used to identify the activator VqmA in Vibrio, wouldn’t you expect to also come across mutations of genes essential for DPO biosynthesis?

Yes indeed. Good eye! We did identify the synthase in the screen. I just did not talk about it in this particular lecture for time/simplification reasons. 

Does the anaerobic environment in the gut impact on these interactions?
We’d love to know that — but we don’t.  We have only recently begun some small experiments in that realm. 
Probably I missed this, but if this were to be used in phage therapy, do you think turning on phage lysis would also affect the beneficial microbiome in the host?

One can (hopefully) engineer the phage therapies to be very specific for a particular pathogen, so the idea is to avoid that. Of course, that has not been proven yet. 

Liam Rooney: Meandering microbes: exploring microbial community architecture using the Mesolens 

How does one get hold of a mesolens?

There are currently four Mesolens systems in operation - three at the University of Strathclyde, Glasgow, and one at the Marine Biology Association, Plymouth. If you wish to apply the Mesolens to your research, then the Mesolab facility at the University of Strathclyde is most equipped to facilitate your request. Currently, specimens may be sent by courier/mail and imaged following a consultation with the Mesolab team. Alternatively, once current restrictions are lifted, there are often opportunities for visiting researchers to use the Mesolens alongside trained facility staff. For more information, please refer to the Mesolab website. 

Chris Proctor: Aerogel delivery of furanones for the inhibition of biofilm formation in Pseudomonas aeruginosa 

I would like to read a bit more on this presentation– is there a reference? 

We recently published a review on the use of furanones as therapeutics in one of the Society’s own journals, Journal of Medical Microbiologyhttps://doi.org/10.1099/jmm.0.001144 

Professor Luke Alphey: Genetic control of mosquitoes 

I've heard that one method to mitigate and control issues with runaway gene-drive systems released in nature, is to release alternate gene-drives that aim to cancel-out/negate the first. Do you think this is a viable strategy or one that is perhaps a bit misguided and could compound the issue?

Gene drives are very varied, both in nature and in the lab; correspondingly issues of spread, reversal, etc vary quite a bit between different designs.  Some gene drives will ‘decay’ away by themselves over time; for some this process can be hastened by releasing specific modified mosquitoes. Some gene drives can be removed from wild populations simply by releasing wild type mosquitoes. These seem quite modest interventions and may well be viable strategies – large-scale release of wild-type mosquitoes does not seem particularly attractive to me, but we are speculating here about a scenario where people would prefer wild-type mosquitoes (no gene drive) to a previously-released gene drive. In some cases, it may be possible to release an alternative version of the gene drive that corrects whatever issue led to the desire to remove it.  So-called “reversal drives” aim to reverse the effect of the drive in the sense of detectable effect on the mosquito (“phenotype”) but will leave a change in the DNA (“genotype”) that would be detectable by laboratory methods. 

In my view, if the gene drive had been initially desirable – and it would have to be to get approval for release – but subsequently less desirable, it might well be possible to build a consensus for replacing it with a better one. For example, if a second-generation version did the same sort of thing only better, or if the first one “wore out” due to emerging resistance, it might be easy to make an argument for a replacement or upgraded version. On the other hand, if the gene drive did something clearly bad – hard to imagine with current designs, but we are speculating here – then I think it might be very hard indeed to persuade people that the best way to deal with that harm might be to release another drive, not least because that harm must have been largely unanticipated before release of the first drive or there would have been no such release. 

Would vector microbiota manipulation be a possibility?

 Yes!  In fact, the only gene drive in field trials at the moment is based on artificial transfer of Wolbachia strains to Aedes aegypti mosquitoes.  Wolbachia are intracellular bacteria transmitted vertically, i.e., like mitochondria rather than like better-known free-living bacteria. They can manipulate their hosts’ reproductive systems to bias reproduction in their favour and can also reduce the ability of some important viruses to replicate in those hosts. For other elements of the microbiota, it seems clear that some aspects of mosquito biology, including key traits such as the ability to transmit viruses, are affected by their microbiota. That suggests the possibility of modifying the microbiota to alter such traits. 

One could imagine modifying specific mosquito-associated bacteria, for example to express novel proteins affecting the mosquitoes – so-called paratransgenesis. This has had some significant proof-of-principle successes in the lab, but not yet progressed to the field, to my knowledge. In principle both Wolbachia trans-infection and paratransgenesis of associated bacteria are similar to modification of the mosquito genome, though with some important differences in detail. One might also be able to modify the microbiota with wild-type microbes, for example changing the complex mix in the mosquito midgut. The interaction between microbiota and mosquito-borne pathogens seems important but, apart from the examples above, how to stably manipulate it in the field to human benefit seems rather unclear at the moment – at least to me!