Researchers at Umeå University have identified how a bacterial protein called RfaH enables pathogens to persist within hostile host environments. The study, led by Kemal Avican from the Department of Molecular Biology and Icelab, uncovers how RfaH safeguards transcription and promotes bacterial survival during infection.
“The human body is a very stressful place for bacteria,” says Avican. “During infection, the immune system attacks, nutrients are scarce, and microbes are exposed to bile salts, acids, and heat. We looked at how RfaH helps bacteria deal with that stress by turning on the right survival genes at the right time.”
Using Yersinia pseudotuberculosis as a model, the researchers found that RfaH acts as an anti-terminator of transcription. The protein attaches to RNA polymerase and prevents premature termination, ensuring full transcription of long operons that encode stress-response and virulence factors. “The protein hops onto the transcription machinery and helps it stay on track so the full set of genes is read to the end,” explains Avican. “When we removed RfaH, the bacteria's ability to establish long-term infection dropped dramatically.”
The team observed that RfaH expression increases during late bacterial growth and under stress conditions. In mouse infection models, strains lacking RfaH infected only about 20% of hosts compared to nearly complete infection by normal bacteria.
Further analysis revealed that RfaH controls the synthesis of the bacterial O-antigen, maintaining the integrity of the outer membrane. It also activates downstream genes involved in adhesion, motility, and nutrient uptake.
“This antimicrobial approach could disarm pathogenic bacteria without disturbing the beneficial ones,” says Joram Kiriga Waititu, first author of the study. The work highlights RfaH-regulated pathways as potential targets for limiting bacterial persistence without broad disruption of the microbiota.
Publication Details
Waititu JK, Nilsson K, Larrouy-Maumus G, Costa TRD, Avican K. 0. RfaH is essential for virulence and adaptive responses in Yersinia pseudotuberculosis infection. mBio 0:e02122-25.
https://doi.org/10.1128/mbio.02122-25
“The human body is a very stressful place for bacteria,” says Avican. “During infection, the immune system attacks, nutrients are scarce, and microbes are exposed to bile salts, acids, and heat. We looked at how RfaH helps bacteria deal with that stress by turning on the right survival genes at the right time.”
Using Yersinia pseudotuberculosis as a model, the researchers found that RfaH acts as an anti-terminator of transcription. The protein attaches to RNA polymerase and prevents premature termination, ensuring full transcription of long operons that encode stress-response and virulence factors. “The protein hops onto the transcription machinery and helps it stay on track so the full set of genes is read to the end,” explains Avican. “When we removed RfaH, the bacteria's ability to establish long-term infection dropped dramatically.”
The team observed that RfaH expression increases during late bacterial growth and under stress conditions. In mouse infection models, strains lacking RfaH infected only about 20% of hosts compared to nearly complete infection by normal bacteria.
Further analysis revealed that RfaH controls the synthesis of the bacterial O-antigen, maintaining the integrity of the outer membrane. It also activates downstream genes involved in adhesion, motility, and nutrient uptake.
“This antimicrobial approach could disarm pathogenic bacteria without disturbing the beneficial ones,” says Joram Kiriga Waititu, first author of the study. The work highlights RfaH-regulated pathways as potential targets for limiting bacterial persistence without broad disruption of the microbiota.
Publication Details
Waititu JK, Nilsson K, Larrouy-Maumus G, Costa TRD, Avican K. 0. RfaH is essential for virulence and adaptive responses in Yersinia pseudotuberculosis infection. mBio 0:e02122-25.
https://doi.org/10.1128/mbio.02122-25