Australian researchers discover new mechanism of antibiotic resistance in Group A Streptococcus

Antimicrobial resistance (AMR) is a silent pandemic claiming the lives of nearly 1.3 million people worldwide each year, and is estimated to result in 10 million deaths annually by 2050.

Scientists are combating AMR  by identifying the different mechanisms that bacteria evolve to resist antibiotics.

Australian researchers have now identified a new antibiotic resistance mechanism in Group A Streptococcus, the bacterium that causes many different infections – from strep throat, to skin infections, and their deadly progression to rheumatic fever.

“We found a mechanism of resistance where the bacteria demonstrated the ability to take folates directly from its human host, when blocked from producing their own,” says co-author Dr Timothy Barnett, Senior Lecturer at the University of Western Australia and Research Fellow at Telethon Kids Institute.

“This makes the antibiotic ineffective and the infection would likely worsen when the patient should be getting better.”

The findings will allow for better testing and treatment for populations most burdened with Strep A infection – Aboriginal and Torres Strait Islander children, and those living in low- and middle-income countries.

The research has been published in Nature Communications.

Credit: Telethon Kids Institute

Circumventing anti-folate antibiotics

Often found in the throat and on the skin, Group A Streptococcus causes about 700 million infections globally each year.

All life needs folate (a B Vitamin) to grow, and bacteria in particular need it to grow and cause disease. Humans get folate through our diet, but bacteria synthesise it themselves, so some types of antibiotics – which includes Sulfamethoxazole and Trimethoprim – block this synthesis to treat infection.

Read more: Antibiotic resistance: an arms race going on millions of years.

The team identified a gene that enables the bacteria to acquire folate from outside of the cell.

Unfortunately, according to Barnett, “This new form of resistance is undetectable under conditions routinely used in pathology laboratories, making it very hard for clinicians to prescribe antibiotics that will effectively treat the infection, potentially leading to very poor outcomes and even premature death.

But why is that the case?

The mechanism isn’t detectable using normal laboratory methods

In the lab, scientists take a sample of the bacteria from an infection and grow it on nutrient medium in the presence of different antibiotics to identify which drugs are effective at stopping growth or killing them.

“We found a mechanism of resistance where the bacteria are only resistant to the antibiotic when they’re causing an infection. So, they’ll test sensitive [to the antibiotic] in a pathology lab, but they’ll be resistant during the infection,” explains Barnett.

This is because the bacteria need the host’s folate to be present to scavenge it, which isn’t the case in laboratory media.

New research into this could lead to the discovery of new AMR mechanisms that are mediated by nutrient availability.

Implications for treating infections

Now that the group have defined the new gene that causes this mechanism of antibiotic resistance it can be tested for.

This is incredibly important, says co-author, Clinical Associate Professor Asha Bowen, a researcher and paediatrician at Perth Children’s Hospital.

“The reason that we’ve explored this folate mechanism is because of clinical work that we’re doing in remote parts of Australia, where we know that the burden of skin infections for remote-living Aboriginal and Torres Strait Islander kids is actually the highest in the world,” says Bowen.

Children who need to be receiving antibiotics to prevent rheumatic fever also include those living in low- and middle-income countries where it is an incredibly problematic condition.

First author Kalindu Rodrigo, a PhD student at the University of Western Australia, will now focus on developing new testing methods to detect this antibiotic resistance mechanism.

“In the context of increasing AMR, it is important to have new diagnostic tools that can rapidly detect antibiotic resistance, including host-dependent resistance. Therefore, we hope to develop rapid point-of-care tests that can be used in remote settings where Group A Strep infections are endemic,” says Rodrigo.

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