"Wolves disguised as sheep": the proud outwit the laboratory tests


According to the new studies, hospital screening tests fail to identify the real extent of microbial resistance.

Scientists have discovered that pathogenic bacteria carry antibiotic resistance genes that are inactive due to a genetic mutation. During screening, the bacteria appear to be susceptible to antibiotics.

"Our results highlight the fact that sometimes antibiotic resistance can be effectively hidden … it seems that you are dealing with an infection that should be curable but that might not be the case."

Dr. Alex O’Neill, University of Leeds

But these mutations are easily lost, rapidly transforming the bacteria into drug-resistant strains, greatly increasing the risk of drug therapy failing.

The study, conducted by the University of Leeds, reveals another level in the complex scientific struggle to understand and combat one of the major challenges for modern health: the rise of drug-resistant superbugs.

Dr. Alex O’Neill, associate professor at the School of Molecular and Cellular Biology in Leeds, said: “Our results highlight the fact that antibiotic resistance can sometimes be effectively hidden. In other words, you seem to be dealing with an infection that should be treatable with a certain antibiotic, but it may not be so. "

The researchers analyzed nearly 1,500 samples of Staphylococcus aureus, a bacterium that is commonly found on the skin but that can cause more serious infections and toxic shock syndrome. It is best known in its highly drug resistant form, MRSA, which often causes a potentially lethal hospital-acquired infection.

In the study, published in the journal mBio, scientists refer to the process by which the drug resistance gene is deactivated as SARM – Silencing of Antibiotic Resistance by Mutation.

About three percent of the samples had the silenced resistance gene and were tested as susceptible to antibiotic treatment.

But in nine out of ten samples in which SARM was identified, the effect of the mutation was quickly lost when the bacteria were exposed to antibiotics.

Antibiotic resistance is rapidly restored

This was due to a process called "inversion" – in fact a second mutation that restored the pathogen to its original and drug-resistant state.

Dr O’Neill said: "The ease with which SARM varieties become drug resistant means that they are" sheep wolves. "SARM is therefore a potentially important reason why antibiotic treatments unexpectedly fail in infected patients.

"We hope that our study will warn physicians of the knowledge that genes of resistance to silenced antibiotics are relatively common in bacteria like S. aureus, and therefore have significant potential to negatively influence antibiotic treatment."

Research reveals a limitation in the routine screening process for drug-resistant bacteria.

Bacteria isolated from patients with a serious infection are subjected to those known as susceptibility tests – tests to determine which antibacterial drugs will be effective in attacking the infection. This is the standard approach, but the research reveals that the test is "blind" in the SARM strains in which the resistance gene is dormant.

Dr O’Neill added: "SARM can be detected using DNA sequencing to determine the complete genetic composition of the strains, but this technology is not yet in routine use in clinical microbiology laboratories."

Although the study examined only S. aureus, researchers believe that this process is likely to occur on other bacteria as well.

Super bug challenge

The NHS states that antibiotic abuse worldwide has accelerated the development of drug-resistant pathogens, so-called superbugs.

The University of Leeds is part of an international struggle to address the threat of antimicrobial resistance with research focused on a number of fronts, from understanding the molecular biology of pathogens, to the best ways to identify bacterial infections and raise awareness 39; public opinion on the need for a rational use of antibiotics.

The research paper is available, "Transient silencing of resistance to antibiotics by mutation represents an important potential source of unexpected therapeutic failure" Here.

Picture: a photo taken with an electron microscope showing Staphylococcus aureus bacteria.



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