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Kemal Avican, Department of Molecular Biology at Umeå University.

Credit: Hans Karlsson

Scientists at Umeå University have discovered a crucial protein that helps bacteria endure the harsh environment inside the human body. Their research shows that a molecule called RfaH serves as a protective mechanism for important bacterial genes, offering fresh ideas for combating lingering bacterial infections.

"Inside the body, bacteria face many threats," explains Kemal Avican, lead researcher at the Department of Molecular Biology and Icelab at Umeå University. “Our immune system targets them, nutrients are limited, and they’re exposed to tough substances like bile and stomach acid. We investigated how RfaH helps bacteria survive these conditions by activating specific genes when necessary.”

Chronic bacterial infections are a growing issue in healthcare, as some bacteria persist in the body long after symptoms subside. This allows them to dodge the immune system and resist common antibiotics, leading to recurring illnesses such as tuberculosis and making treatment more complex.

Keeps Essential Genes Active

Research using the gut-infecting bacterium Yersinia pseudotuberculosis demonstrated that RfaH is vital for the bacteria to persist in a host.

RfaH works by stabilizing transcription—the cellular process that turns DNA into messenger RNA, which in turn builds proteins. It acts as a support system, ensuring that genetic instructions are carried out fully and accurately.

"What RfaH does is link itself to the transcription machine and keep it working continuously, ensuring the entire genetic message is processed," says Kemal Avican. "Without this protein, the bacteria were far less able to maintain long-term infections."

Helping Bacteria Endure Hostile Stress

The team observed that bacteria increase their production of RfaH during their later growth stages and particularly when under stress.

In testing with mice, the results clearly showed that while most mice were infected by normal bacteria, only about 20% became infected with RfaH-deficient strains. The remaining mice had significantly better survival chances.

Bacterial genes are often located in long DNA sequences known as operons. Without RfaH, the molecular machinery that reads these sequences sometimes halts too early, missing important instructions. With RfaH present, bacteria are better able to build surface structures, release toxins, and withstand the body’s defense mechanisms.

Potential for New Treatment Approaches

The study also found that RfaH controls the formation of O-antigen, a key part of the bacterial outer membrane. Without RfaH, the membrane is improperly formed. Moreover, RfaH activates many additional genes involved in bacterial functions such as sticking to surfaces, movement, and nutrient absorption.

Since RfaH appears in both harmful and harmless bacteria, the researchers believe targeting the specific genes regulated by RfaH—rather than the protein itself—might allow the development of antimicrobial treatments that spare beneficial gut flora.

"This could be a way to fight harmful bacteria without harming the good ones that naturally live in and support our bodies,” says Joram Kiriga Waititu, a postdoctoral researcher in the Molecular Biology department and the primary author of the study.

Though Yersinia pseudotuberculosis infections generally resolve on their own, they provide a model for understanding other gut bacteria, including Escherichia coli, Salmonella, and Helicobacter, which are capable of causing more severe and recurring illnesses. These insights may help develop treatments for bacterial infections that are difficult to eliminate.

The study was featured in the scientific journal mBio and was financially supported by the Swedish Research Council, Umeå Centre for Microbial Research (UCMR), the Stress Response Modeling at IceLab Centre of Research Excellence, Kempestiftelserna, and the Medical Faculty at Umeå University.

Journal

mBio

DOI

10.1128/mbio.02122-25

Method of Research

Experimental study

Subject of Research

Animals

Article Title

RfaH is essential for virulence and adaptive responses in Yersinia pseudotuberculosis infection

Article Publication Date

29-Sep-2025