Flipping the switch on antibiotic resistance: The role of riboswitches in bacterial survival

As part of Lab Week, our Lab4Life feature hosts a special series highlighting the inspiring journeys of scientists dedicated to clinical science and global health. In this guest blog, Dr. Umama Shahid discusses her research on combatting antimicrobial resistance (AMR).

AMR is one of the biggest challenges facing healthcare today, making infections harder to treat and increasing the risk of untreatable diseases. As a researcher at Monash University's School of Science in Malaysia, Dr. Shahid is dedicated to understanding bacterial resistance mechanisms at the molecular level. Alongside her colleagues, she explores innovative approaches to combat AMR, focusing on riboswitches — RNA-based regulatory elements that help bacteria adapt to antibiotic stress.

Recognizing the importance of medical laboratory professionals in diagnosing and managing AMR, discover how Dr. Shahid sees LabWeek as a crucial opportunity to highlight the scientific breakthroughs that support global health efforts.

Screening for riboswitches

Riboswitches are small segments of RNA found in bacterial mRNA that act like switches. They bind to specific molecules — like metabolites or metal ions — and control whether certain genes get turned on or off. While riboswitches are known to regulate metabolic functions in bacteria, their role in antibiotic resistance hasn’t been studied much. That’s where my work comes in.

I focused on Klebsiella pneumoniae because it's highly resistant to antibiotics, including last-resort options like carbapenems. Using advanced sequencing techniques (RNA-seq and term-seq), I screened for riboswitches that respond specifically to ampicillin. Out of 163 possible candidates, I narrowed it down to three riboswitches that showed clear, specific responses to ampicillin. These riboswitches acted like molecular sensors — switching certain genes on or off to help the bacteria survive antibiotic stress.

A new antibiotic target

Understanding how bacteria use riboswitches to resist antibiotics opens up exciting new possibilities for treatment. Most antibiotics target bacterial proteins, but bacteria are getting better at evolving ways to protect those targets. Riboswitches, on the other hand, are part of the RNA itself — a different and less explored target. If we can develop drugs that interfere with riboswitch activity, we might be able to stop bacteria from activating their resistance mechanisms in the first place.

The riboswitches I identified didn’t just respond to ampicillin — they also showed specificity toward other β-lactam antibiotics. This suggests they could be targeted to create a new class of antibiotics designed to outsmart resistant bacteria.

Validating riboswitch response

One challenge was making sure that these riboswitches were responding to ampicillin and not just random noise. To confirm their function, I used sophisticated fluorescence-based reporter assays and biochemical tests like electrophoretic mobility shift assays (EMSA), which showed that the riboswitches physically bind to ampicillin. This was key to proving that they weren’t coincidentally activated under stress.

A promising future

Moving forward, these riboswitches could be the foundation for designing new antibiotics or treatments that target bacterial RNA directly. This could help sidestep traditional resistance pathways and give us a new weapon in the fight against superbugs. This research highlights how much potential there is in exploring RNA-based mechanisms in bacteria.

While protein-targeting antibiotics are becoming less effective, riboswitches offer a fresh angle — one that could lead to smarter, more targeted therapies.

Antibiotic resistance isn’t going away anytime soon, but understanding how bacteria survive and adapt at the molecular level might just give us the edge we need.

Visit the Lab4Life feature page to read more like this>>

Connect with Dr. Umama Shahid on LinkedIn>>