In patients fighting severe lung infections, resistance to a powerful antibiotic can sometimes spike thousands of times over within days of treatment beginning — far faster than the slow, mutation-by-mutation process doctors have long relied on to anticipate and manage resistance.

Researchers at the University of Washington School of Medicine studying people with cystic fibrosis, who develop serious chronic lung infections requiring intensive antibiotic treatment, found cases where resistance rose by more than 10,000-fold shortly after treatment started — far too fast to fit the standard model of gradual resistance through genomic mutation. Lead author Sardar Karash sequenced hundreds of bacterial isolates from patient samples using conventional short-read sequencing and found no mutations that could explain the jump. Switching to long-strand sequencing revealed the real cause: the lung pathogens had picked up circular pieces of DNA called plasmids carrying entirely new resistance genes.

When Karash introduced those same genes into drug-sensitive bacteria in the lab, their resistance rose accordingly, confirming the plasmids were responsible. Tracing the source, the team found that environmental bacteria — organisms not typically considered dangerous because they’re not very virulent and tend to appear in the lungs only briefly — showed up transiently in some patients’ lung samples just before resistance emerged, carrying identical resistance plasmids and capable of transferring them directly to the pathogens already established there.

Karash noted that resistance developing inside a patient was long thought to result from a gradual accumulation of mutations in the bacterial genome, which gave physicians time to react; this pattern upends that assumption. Colin Manoil, a genome sciences collaborator who helped with the long-strand sequencing, confirmed that the pathogens had acquired these plasmids directly. Senior author Pradeep Singh warned that these environmental bacteria may carry other genes beyond resistance — ones that could help pathogens scavenge nutrients, evade immune responses, or break down barriers that would otherwise limit infection, saying they can carry genes that can do almost anything. The researchers, whose work was funded by the Cystic Fibrosis Foundation and the National Institutes of Health, hope that environmental monitoring and containment, paired with new strategies to block gene transfer, could reduce the risk going forward.

Journal: Nature Microbiology
Article Title: Environmental bacteria enter lungs during an infection and transfer antibiotic resistance genes to disease-causing bacteria
DOI: 10.1038/s41564-026-02414-3
Publication Date: July 23, 2026

Source: EurekAlert