DNA sequencing could predict MRSA infection outcome

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MRSA is responsible for an array of difficult-to-treat infections in humans, wherein the emergence of antibiotic resistance is a global public health concern. S. aureus commonly lives on skin, however, penetration into the body through a cut can lead to septicemia – an infection that affects thousands of patients every year in the UK.

Researchers from the University of Bath (Bath, UK) adopted a genome-wide association study approach to analyze blood samples from 3000 patients with septicemia from two different strains of MRSA – CC22 and CC30. They evaluated the bacterial genotype and phenotype together with clinical metadata and found that clonal differences in the determinants were able to predict infection outcome (i.e., the probability of a patient surviving the MRSA infection).

The investigators also observed the ability of MRSA to form biofilms, which occur when groups of bacteria secrete proteins that cause them to adhere to one another. This network of adhered cells can become embedded into a ‘slimy’ extracellular matrix and can make it easier for bacteria to evade the patient’s immune system, as well as block the action of antibiotics.

Ruth Massey (University of Bath), the lead researcher in the study published in Nature Microbiology, explained: “Our study is important because it’s the first time we’ve collected data in human patients rather than relying solely on animal models.

“For the first time we’ve been able to predict which strains are most virulent, or likely to cause disease, and the outcomes of infection.”

The results indicated that in CC22 strains, both toxicity and biofilm-forming abilities played a significant role in whether the patient survived MRSA infection. However, in CC30 strains, this wasn’t the case – indicating that this particular strain may be causing fatalities via an alternative mechanism. According to the study, “different clones may have adopted different strategies to overcome host responses and cause severe pathology.”

Massey added: “We’ve identified that MRSA kills people in different ways depending on the strain, and that the low-toxicity CC30 strains are killing patients in an as yet unknown mechanism. It could be that they are better at evading the immune system. We need further research to find out how they do this, in order to develop new treatments for these patients.”

The researchers concluded: “Our study further demonstrates the use of a combined genomics and data-analytic approach to enhance our understanding of bacterial infection at the individual level, which will be an important step towards personalized medicine and infectious disease management.”

Source: Recker M, Laabei M, Toleman MS et al. Clonal differences in Staphylococcus aureus bacteraemia-associated mortality. Nat. Microbiol. doi:10.1038/s41564-017-0001-x (2017) (Epub ahead of print); www.eurekalert.org/pub_releases/2017-08/uob-msc080717.php

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