Sequencing super bacteria hopes to be with the difficulties

At the end of 2011, researchers at a hospital in the United Kingdom determined that all MRSA strains in the hospital were related by high-resolution genome sequencing technology, and the disease outbreak was promptly curbed.

Release date: 2014-08-29

At the end of 2011, several babies in a British hospital were infected with methicillin-resistant Staphylococcus aureus (MRSA). Subsequently, a research team at the Wellcome Trust Sanger Institute began analyzing samples of these cases. They want to determine if these infections constitute an outbreak. In general, the hospital's data is not so clear; there is a gap in the timeline of case transmission, making it difficult to conclude whether there has been an outbreak in the past six months. The doctors then contacted the research team. At this point, the new case suddenly appeared in the same ward.

The team analyzed the new MRSA sample and confirmed that the new case was part of the original outbreak. Thanks to high-resolution genome sequencing technology, the researchers were able to tell the doctor that all MRSA strains in the hospital were relevant despite gaps in the timeline of transmission. In addition, the data indicates that this is an internal problem and that a staff member is likely to act as a carrier of MRSA infection. So they sampled and sequenced 150 staff members. In an article published in The Lancet-Infectious Disease, the researchers identified a health care provider as a carrier. This person was isolated, treated, and returned to work. Since then, there has been no MRSA infection in the hospital.

According to Julian Parkhill, a microbiologist at the Sanger Institute, this is very exciting. “This is the first time that genome sequencing has been applied in real time to intervene in an outbreak. Without sequencing, a new case is not enough for us to take action.”

Looking ahead, Parkhill believes that DNA sequencing will be routinely used to understand the outbreak of these resistant bacteria. In the case of a British hospital, if sequencing is used from the beginning, the outbreak may stop after the first case has occurred.

Changing clinical practice

For the time being, hospitals mostly use lower resolution methods to identify bacteria, such as PCR analysis. Although multilocus sequence typing (MLST) is sometimes used for multi-drug infections, such as MRSA, it is also problematic because hospital-related infections are often caused by bacteria belonging to the same sequence type. This level of resolution does not give the doctor the information needed to isolate the source of infection. In addition, each different organism requires a specific typing reagent, and sequencing is a method that is suitable for all bacteria.

Genomic sequencing may be particularly useful in cases of Gram-negative resistant bacteria, especially those that are resistant to carbapenems. In 2011, the NIH Clinical Center in the United States discovered a Klebsiella infection resistant to carbapenem. 2 Researchers used genome sequencing to gain insight into the outbreak process and built a phylogenetic tree to show that infections are interrelated. This analysis clearly shows how bacteria spread between patients.

Although sequencing is not standard, the information obtained from the research has changed clinical practice. "We understand that we need to be more proactive in patient monitoring, and we have always been honest because we don't want it to happen to anyone," said Julia Segre of the National Human Genome Research Institute.

Sharon Peacock, a clinical microbiologist at the University of Cambridge, said sequencing could also help with tuberculosis. It takes about a few weeks or more to complete the antibiotic resistance test for tuberculosis. At the same time, patients must be treated with antibiotics without knowing if this is effective. With sequencing, patients may receive effective antibiotic treatment within a few days.

Why is it not regular?

If genome sequencing can tell us so much about infection, why is it not routine to use? Before the hospital launched this type of analysis, the supporting infrastructure had yet to be developed. The biggest obstacle is the development of a reference database for the bacterial genome.

“In order to analyze any isolate, you need a database and put it in a genetic and geographic context,” Peacock said. This will allow newly sampled bacteria to be analyzed faster. Ideally, scientists build an automated system that effectively encodes the expertise that researchers use to conduct analysis today. In this way, the doctor puts a sample and gets a report that can be used.

Segre added: “We also need reference genomes that are sequenced with different instruments, which can lead to slightly different results. We need to know which differences come from the sequencing platform and which are the true evolution from bacteria.”

Although recent studies using whole genome sequencing to analyze MRSA and Klebsiella have shown that this technique is effective, the next step is to prove cost-effective. “We have to let health economists and doctors look at the costs. Research in this area has not yet begun,” Peacock said.

Because bacteria have far fewer genes than humans, the cost of whole-genome sequencing is about $100-$200. Of course, the cost of sequencing, data analysis, and reference database development is not included in this figure. “We also need to conduct a detailed survey of costs and benefits,” Peacock said. “Where does this technology work and where does it work?”

In some cases, sequencing does work well, but it doesn't give you information about the disease process. In terms of cost control, sequencing is the key when needed. As for sequencing costs and turnaround time, "we don't need to do anything to make it fall," Parkhill said. “Now the human genome sequencing is already a huge market, which is also well translated into microbial sequencing.”

Source: Biopass

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