Lightning Talk about Capsule Switching in Streptococcus pneumoniae by Anna York
March 21, 2024Information
Anna York, BSc (Hon), PhD, Associate Research Scientist in Epidemiology (Microbial Diseases); Affiliated Faculty, Yale Institute for Global Health.
In the video, Anna talks about her research which focuses on investigating metabolic and genetic restrictions that may determine which serotypes can undergo capsule switching in Streptococcus pneumoniae. An improved understanding of capsule switching could lead to better prediction of serotype replacement events and inform on serotype selection for next generation polysaccharide conjugate vaccines (PCVs).
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- 00:02So, hi everyone.
- 00:04Yeah, I'm an associate research
- 00:05scientist in Dan Weinberger's lab,
- 00:07and I'm going to give you a very
- 00:10brief overview on what I do broadly.
- 00:12So I work on a bacteria called
- 00:15Streptococcus pneumoniae.
- 00:16Is that better? Yeah.
- 00:17OK. Sorry.
- 00:18I work on Streptococcus pneumoniae,
- 00:20which is a a bacteria that resides
- 00:25asymptomatically in the nasopharynx
- 00:27of many adults and children worldwide.
- 00:30But it is also a opportunistic
- 00:33pathogen and can cause a range of
- 00:37disease from milder diseases such
- 00:39as sinusitis and otitis media,
- 00:41up to more severe disease known as
- 00:44invasive pneumococcal disease IPD,
- 00:46which includes pneumonia,
- 00:48meningitis, bacteremia, sepsis.
- 00:53There are over 100 different stereotypes
- 00:55of pneumococcus and a stereotype is
- 00:58basically defined by the the capture the
- 01:00polysaccharide that is on the outermost,
- 01:03the outermost layer of the bacterium.
- 01:06And the vaccines that we have currently
- 01:09are targeting this sugar coating,
- 01:11this capture the polysaccharide
- 01:14and the introduction of vaccines.
- 01:15We saw a dramatic decrease in
- 01:18disease caused by vaccine serotypes.
- 01:21So those that were included in the
- 01:24vaccine but somewhat unexpectedly
- 01:25there was a very rapid emergence
- 01:27of non vaccine stereotypes.
- 01:29So those that were not included that
- 01:31were previously not causing much disease.
- 01:32And so now you know you have this problem
- 01:35where you're kind of chasing a tail
- 01:37trying to adapt a vaccine and building
- 01:39this the currently problematic stereotypes.
- 01:41But the major limitation is that we have
- 01:44a kind of a limitation to the valency,
- 01:46so the number of different stereotypes
- 01:48that we could include in anyone vaccine.
- 01:51So the this kind of reemergence or
- 01:53emergence of different serotypes
- 01:55is termed serotype replacement.
- 01:57And there are kind of two mechanisms
- 01:59to this happening.
- 02:00One is unmasking which is where the
- 02:02niche is just kind of cleared of
- 02:04that serotype that was present making
- 02:06room for a new serotype there to just
- 02:08kind of move in and and do its thing.
- 02:10And then the other one is serotype
- 02:12switching and this is where a vaccine
- 02:15type lineage acquires a non vaccine
- 02:17type capsule and kind of is able to hide
- 02:19you know and now unaffected from the vaccine.
- 02:21And so this is just a
- 02:23little image showing you.
- 02:24So this serotype 4 for instance
- 02:26has its blue backbone,
- 02:28the genetic backbone and the 19
- 02:30A capsule is switching onto it.
- 02:32And so you kind of end up with this
- 02:34capsule switch variant on the the end
- 02:36where it's now switched to a different thing.
- 02:40And if if the 19 A wasn't included in
- 02:42the vaccine you would be able to this
- 02:43would be able to evade that mechanisms.
- 02:45So I'm super interested in capsule switching,
- 02:49both intra and interspecies
- 02:50capsule switching.
- 02:51There are streptococci that also
- 02:53reside in the nasopharynx and
- 02:55oropharynx that also possess capsules
- 02:57somewhat similar to the pneumococcus.
- 03:00And so yeah, I'm interested in the switching.
- 03:01We do switches in vitro.
- 03:03We look at genetic and metabolic
- 03:06restrictions on which of these
- 03:07stereotype pairs can and can't
- 03:09switch and which lineages can,
- 03:11and then with the aim of looking
- 03:13at the underlying mechanisms to
- 03:14this and establishing their fitness
- 03:16when they have switched.
- 03:17So we look at growth characteristics,
- 03:19the expression of the capsule,
- 03:21and then in vivo models looking
- 03:24at colonization and disease.
- 03:26And the idea of understanding this
- 03:28and having this detailed information
- 03:30would be that we can better predict
- 03:33which stereotypes are likely to
- 03:35become problems in the future and
- 03:37kind of use surveillance data,
- 03:39carriage data to kind of establish these,
- 03:41a set of rules that we can,
- 03:45yeah,
- 03:45understand which ones we should
- 03:47be focusing on and
- 03:49which ones should be considered
- 03:51or prioritized for inclusion
- 03:53in subsequent vaccines.
- 03:55We also do some assay development
- 03:57and we developed this assay
- 03:59which helps us extract or enrich
- 04:02samples of mixed stereotypes for
- 04:04a particular stereotype interest.
- 04:06And so here you can see the orange
- 04:08stereotype is the one that's of interest.
- 04:09We use an antibody and a magnetic bead
- 04:12to kind of pull out that from a mixture.
- 04:16This can help us do our capture
- 04:17switching experiments,
- 04:18but it can also be used to take
- 04:21out stereotypes from complex
- 04:22polymicrobial samples such as saliva.
- 04:25So if you have a stereotype of
- 04:26interest that you want to look at,
- 04:27you can basically pull it out using
- 04:29this and it can also work on those non
- 04:32pneumococcal streptococci species.
- 04:33So if we're interested in looking
- 04:35at that those we can do it as well.
- 04:37So this is just super quick overview of
- 04:39the types of techniques that we have.
- 04:41We use micro a lot of microbiology
- 04:44techniques,
- 04:44molecular techniques and the current
- 04:46projects that I'm working on as
- 04:48I've kind of mentioned and hinted
- 04:49towards is capsule switching,
- 04:51looking at the genetics of the
- 04:53importance of non capsular genes
- 04:56in supporting these variants,
- 04:58how different adaptations may
- 04:59be in metabolic things.
- 05:01Certainly sugar metabolism might
- 05:04kind of limit or promote certain
- 05:08switching and the identification of
- 05:11these non pneumococcal stereotypes
- 05:13in for instance saliva samples and
- 05:15then also the role of unencapsulated
- 05:18pneumococci on receiving capsules
- 05:20in kind of this emergence.
- 05:22So, yeah, thank you very much.