A newly published pair of studies from researchers at the University of Florida, Hokkaido University, and partners in Thailand and Japan has shed light on how Burkholderia pseudomallei—the bacterium responsible for the often-deadly disease melioidosis—can outsmart one of the most important drugs used to treat it.
The work, appearing in Antimicrobial Agents and Chemotherapy and Microbiology Resource Announcements, examined dozens of drug-resistant bacterial samples from patients in northeast Thailand and mapped the entire genome of a particularly important strain. The research uncovers both a brand-new genetic mutation and a structural quirk in the bacterium’s DNA that allow it to survive treatment with ceftazidime (CAZ), a critical antibiotic in many parts of the world.
A New Mutation with Big Consequences
The team discovered a previously unknown genetic change, called A172T, in a gene named penA. This gene produces an enzyme that can break down certain antibiotics before they can work. The A172T mutation alters the enzyme in a way that makes the bacteria up to 16 times more resistant to ceftazidime.
In lab tests, simply adding this mutation to an otherwise drug-sensitive strain was enough to make it highly resistant—strong evidence that A172T is a key driver of treatment failure.
DNA “Copy-and-Paste” Resistance
Beyond single-letter mutations, the studies also revealed another clever survival tactic: gene duplication and amplification. In some resistant strains, the bacteria carried multiple extra copies of the penA gene—sometimes as many as nine. More copies mean more of the antibiotic-destroying enzyme.
Researchers traced this to unusual palindromic GC-rich repeat sequences in the DNA. These repetitive patterns seem to act like “genetic Velcro,” causing the DNA to fold and recombine under drug pressure, effectively copy-pasting penA over and over.
One fully mapped strain, called 490f, carried three penA copies inside a large and complex repeat section of its DNA. Untangling this section required high-tech genome sequencing and painstaking manual assembly.
Other Routes to Resistance
The team also identified changes in the penA promoter region—essentially the gene’s “on/off” switch—that cranked up enzyme production. And in some cases, combinations of mutations subtly altered the enzyme’s shape, allowing it to resist multiple drugs in the same family.
While B. pseudomallei does not typically pick up resistance genes from other bacteria via plasmids (a common route in many pathogens), its ability to mutate and rearrange its own DNA gives it plenty of evolutionary flexibility.
Why It Matters Beyond the Lab
Melioidosis is a serious public health challenge in tropical regions, causing high death rates even with treatment. It’s also considered a Tier 1 select agent in the United States because of its potential misuse as a biothreat. Losing ceftazidime as a reliable treatment option would complicate outbreak control and put both local communities and global health security at greater risk.
For everyday public health, this means that drug resistance in B. pseudomallei is not just an abstract lab problem—it has direct implications for the safety of drinking water, soil contact in rural communities, and medical preparedness for travelers and military personnel in affected areas.
Looking Ahead
The authors suggest several steps:
- Surveillance to spot A172T and similar mutations early.
- Faster diagnostics that can detect known resistance markers right in the clinic.
- Deeper research into the DNA structures that drive gene duplication.
- Lab simulations to see how resistance emerges under incomplete or incorrect dosing.
By understanding how this bacterium develops resistance, scientists and public health agencies can better protect the antibiotics we have—and buy time to develop new ones.
Sources and Further Reading:
Tuanyok A, Nakajima C, Noll T, et al. Genomic insights into ceftazidime resistance in Burkholderia pseudomallei: discovery of A172T mutation and palindromic GC-rich repeat sequences facilitating penA duplication and amplification. Antimicrobial Agents and Chemotherapy, 21 July 2025.
Khrongsee P, Subramaniam K, Mergia A, Tuanyok A. Complete genome sequence of ceftazidime-resistant Burkholderia pseudomallei strain 490f reveals a complex long repeat region. Antimicrobial Chemotherapy, 11 August 2025