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Pacific Biosciences

SMRT Grant Winner: Preventing Infection for Premmies

Monday, November 5, 2018

Mark Webber

We’re pleased to announce the winner of the 2018 Microbial Genomics SMRT Grant. Mark Webber, Research Leader at Quadram Institute Bioscience in the UK, will get free SMRT Sequencing and analysis from our certified service provider, the Genomics Resource Center at the University of Maryland.  His goal is to further a project designed to understand how bacteria on the skin of premature babies in neonatal intensive care units acquire resistance to the antiseptics used to prevent infections. We spoke with Mark to learn more about his work and how the SMRT Grant will make a difference.


Q: What’s your research focus?

A: We’re interested in how bacteria deal with stress — how do bugs become resistant to drugs? We’re particularly interested in Staphylococci and how they deal with the antiseptics that we use in hospitals. We’ve looked at patients in intensive care in the UK, examining isolates over time to see how susceptible they were to two antiseptics in a large teaching hospital that had changed its antiseptic use. What we could see was that as you used more and more chlorhexidine, the bugs were more and more tolerant. When they introduced another antiseptic; octenidine, a population quickly emerged that was less tolerant of octenidine.


Q: What inspired the proposal you submitted for this SMRT Grant?

A: We have been studying premature babies in neonatal intensive care. Every year about 450,000 premature babies are born in the US and 60,000 are born in the UK. About 15,000 of these| will suffer from late-onset sepsis. mainly caused by Staphylococci infections. These babies are often very immune-suppressed and the risk of death from sepsis is quite high. The babies almost all have peripheral catheters to allow feeding and drugs to be administered but these are a potential route for bugs to get in to their blood. Therefore, to prevent infection from bugs living on the skin there’s a lot of antiseptic use. We wanted to see how antiseptic tolerance might be developing amongst the bugs living on the skin of these premature babies.


Q: What have you learned so far about this issue?

A: At hospitals in the UK and with our collaborators in Germany, we collected isolates each week from hundreds of babies over a three-month period. We now have a total of 1,300 isolates of Staphylococci which we have tested for their susceptibility to chlorhexidine, the antiseptic used in the UK, and octenidine, the antiseptic used in Germany. We have seen that babies in intensive care appear to pick up Staphylococci with high tolerance to antiseptics very quickly and our UK population is particularly robust in dealing with chlorhexidine which we use.


Q: How will you use the sequencing capacity from your SMRT Grant?

A: After studying all 1,300 isolates, we want to understand how related these bacteria are and take about 20 representatives of the major branches of the Staphylococcal family tree and get really high-quality, full genome sequences. With the PacBio long reads, we will be able to see whether there are common mobile elements that explain the acquisition of tolerance. We can also look for duplications, rearrangements, and methylation patterns which may be responsible for antiseptic adaptation. PacBio sequencing will give us a higher quality picture of what’s going on than other technologies, and this SMRT Grant will let us capture most of the major branches of the phylogeny that we’re hoping to see.


Q: What do you hope to learn when you’ve had a chance to analyze these new reference genomes?

A: Doing the bioinformatics analysis will not take us that long — it should be a matter of a few days to get a pretty decent picture of what differs between antiseptic tolerant and sensitive strains. We hope to understand the mechanisms of resistance that we can then compare to isolates collected in other parts of the world. That will help us determine whether antiseptic use is likely to fail, whether different antiseptics are more or less likely to select for tolerance and whether antiseptic tolerance is linked to antibiotic resistance. Together this information should help us understand whether we need to change the way we use antiseptics to keep babies safe.


We’re excited to support this research and look forward to seeing the results. Check out our website for more information on upcoming SMRT Grant Programs for another chance to win SMRT Sequencing. Thank you to our co-sponsor, the University of Maryland’s Genomics Resource Center, for supporting the Microbial Genomics SMRT Grant Program!

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