ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Molecular Bacterial Pathogenesis
Involvement of HemI, an ECF sigma factor, in hemin acquisition and antibiotic susceptibility in Stenotrophomonas maltophilia
Provisionally accepted
- 1Far Eastern Memorial Hospital, New Taipei, Taiwan
- 2National Yang Ming Chiao Tung University - Yangming Campus, Taipei City, Taiwan
- 3Asia University, Taichung, Taiwan
- 4Taipei Veterans General Hospital, Taipei City, Taiwan
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Background: Hemin is a major source of iron for pathogens in infectious niches. The FecIRA-like surface signaling cascade is a common regulatory system for iron acquisition by pathogens. This system consists of a FecA-like TonB-dependent transporter (TBDT), a FecR-like inner-membrane anti-sigma factor, and a FecI-like extracytoplasmic function (ECF) sigma factor. Beyond iron acquisition, FecIRA-like systems have been reported to regulate additional physiological processes. The known hemin acquisition system in Stenotrophomonas maltophilia includes HemA, a TBDT; HemU, an inner-membrane transporter; and the TonB1-ExbB1-ExbD1a-ExbD1b complex, a multi-subunit motor that energizes HemA. Fur and HemP are the primary regulators involved in hemin utilization. In this study, we identified a novel FecIRA-like regulatory system, HemI-HemR-HemAD. Methods: The regulatory role of HemI was examined using promoter-xylE transcriptional fusion constructs and Real-time PCR. Mutants associated with the hemI-hemR-hemAD operon were generated and evaluated for iron utilization, swimming motility, oxidative stress tolerance, and antibiotic susceptibility. This is a provisional file, not the final typeset article Results: The hemI-hemR-hemAD operon was repressed by Fur-Fe2+ under iron-replete conditions. Its expression was partially derepressed under iron depletion and further derepressed in the presence of hemin; however, the operon showed no autoregulation. HemI was essential for hemin acquisition. Overexpression of hemI in the S. maltophilia KJ strain increased susceptibility to levofloxacin (LVX) and trimethoprim-sulfamethoxazole (SXT). All S. maltophilia isolates tested displayed increased MICs for ceftazidime (CAZ) and minocycline (MIN) under iron-depleted and hemin-available conditions; notably, changes in MICs for LVX and SXT were strain-dependent. Conclusion: HemI, a novel ECF sigma factor, not only regulates hemin acquisition but also contributes to antibiotic susceptibility under iron-limited and hemin-available conditions.
Keywords: Stenotrophomonas maltophilia, Sigma Factor, HEMI, HemR, hemin acquisition, surface signaling cascade
Received: 11 Oct 2025; Accepted: 21 Nov 2025.
Copyright: © 2025 Liao, Ku, Lu, Hu, Li and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Tsuey-Ching Yang, tcyang@nycu.edu.tw
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