Using Whole-Genome Sequencing to Control Hospital Infection
Using Whole-Genome Sequencing to Control Hospital Infection
Basic hospital infection control measures, such as disinfecting surfaces and ensuring doctors and nurses wash their hands between patients, dramatically lower infection rates. But bacteria can survive for long periods, even after vigorous disinfection procedures, and WGS analysis has shown they are able to travel via pathways no one had predicted. Although these transportation events and hiding spots might go unseen, researchers hope that looking directly at the bacterial genomes may reveal bacterial strain circulation.
The first organism to have its entire genome sequenced was the common respiratory pathogen Haemophilus influenzae, a procedure first reported in 1995 that cost around $1 million and took more than a year. At the same time, scientists began moving toward ways of identifying bacteria using their DNA, even if it didn't involve identifying every last nucleotide. In one method, pulsed-field gel electrophoresis (PFGE), the bacterial genome is chopped into small pieces using enzymes that split DNA near certain nucleotide sequences known as restriction sites. The fragments are then separated by size, and the pattern of fragments creates a unique fingerprint for different types of bacteria. Other methods sequence only certain parts of the bacterial genome, which lets researchers identify different aspects of the pathogen they are looking at, such as species and genetic markers that could help determine which bacteria were part of which outbreak—something that isn't always possible with PFGE.
"Older methods of investigating outbreaks were done by methods that were, by comparison [with WGS], incredibly crude," says William Hanage, a microbiologist at Harvard University. "You would chop up the DNA … and you'd get a banding pattern on a gel. And you'd hold that up to the light and squint at it and say whether two isolates had the same banding pattern."
In contrast, genomes provide much more detail and enable much more precision in determining which pathogens are being transmitted and how it is happening. "Genomics is going to revolutionize infection control," Hanage says. "We're going to have genome sequencing of isolates as a matter of course."
The first automated gene sequencers used a method developed by British biochemist Frederick Sanger, and, by the late 1990s, could sequence 2.88 million bases per day in sections up to 900 base pairs long. WGS—also referred to as high-throughput or next-generation sequencing—first became commercially available in 2005 and could sequence many genomes at the same time. These systems could sequence only shorter sections of DNA that had to be laboriously pieced back together into a full genome, but they had the advantage of allowing more sequencing at a lower cost.
Despite these improvements, the process was still relatively slow. "In the early stages of next-generation sequencing technology it would take ten to fourteen days from a patient having an infection to getting a genome sequenced, and that's not fast enough for infection control," says University of Michigan microbiologist Evan Snitkin. Today, Snitkin says, the newest technology can turn around results in a matter of hours. And while many investigators still culture the samples they collect before performing WGS, there is evidence that clinical samples can be tested directly and reliably.
(Enlarge Image)
No Time to Waste
Basic hospital infection control measures, such as disinfecting surfaces and ensuring doctors and nurses wash their hands between patients, dramatically lower infection rates. But bacteria can survive for long periods, even after vigorous disinfection procedures, and WGS analysis has shown they are able to travel via pathways no one had predicted. Although these transportation events and hiding spots might go unseen, researchers hope that looking directly at the bacterial genomes may reveal bacterial strain circulation.
The first organism to have its entire genome sequenced was the common respiratory pathogen Haemophilus influenzae, a procedure first reported in 1995 that cost around $1 million and took more than a year. At the same time, scientists began moving toward ways of identifying bacteria using their DNA, even if it didn't involve identifying every last nucleotide. In one method, pulsed-field gel electrophoresis (PFGE), the bacterial genome is chopped into small pieces using enzymes that split DNA near certain nucleotide sequences known as restriction sites. The fragments are then separated by size, and the pattern of fragments creates a unique fingerprint for different types of bacteria. Other methods sequence only certain parts of the bacterial genome, which lets researchers identify different aspects of the pathogen they are looking at, such as species and genetic markers that could help determine which bacteria were part of which outbreak—something that isn't always possible with PFGE.
"Older methods of investigating outbreaks were done by methods that were, by comparison [with WGS], incredibly crude," says William Hanage, a microbiologist at Harvard University. "You would chop up the DNA … and you'd get a banding pattern on a gel. And you'd hold that up to the light and squint at it and say whether two isolates had the same banding pattern."
In contrast, genomes provide much more detail and enable much more precision in determining which pathogens are being transmitted and how it is happening. "Genomics is going to revolutionize infection control," Hanage says. "We're going to have genome sequencing of isolates as a matter of course."
The first automated gene sequencers used a method developed by British biochemist Frederick Sanger, and, by the late 1990s, could sequence 2.88 million bases per day in sections up to 900 base pairs long. WGS—also referred to as high-throughput or next-generation sequencing—first became commercially available in 2005 and could sequence many genomes at the same time. These systems could sequence only shorter sections of DNA that had to be laboriously pieced back together into a full genome, but they had the advantage of allowing more sequencing at a lower cost.
Despite these improvements, the process was still relatively slow. "In the early stages of next-generation sequencing technology it would take ten to fourteen days from a patient having an infection to getting a genome sequenced, and that's not fast enough for infection control," says University of Michigan microbiologist Evan Snitkin. Today, Snitkin says, the newest technology can turn around results in a matter of hours. And while many investigators still culture the samples they collect before performing WGS, there is evidence that clinical samples can be tested directly and reliably.
(Enlarge Image)
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