Experimental evolution reveals temporally opposing roles for Csu pili during Acinetobacter baumannii respiratory infection
- 1Washington University in Saint Louis School of Medicine
Abstract
Multidrug-resistant (MDR) Acinetobacter baumannii is an opportunistic pathogen responsible for a wide range of infections, including ventilator-associated pneumonia, bloodstream infections, and urinary tract infections. Most studies investigating A. baumannii pulmonary pathogenesis rely on acute pneumonia models that use high bacterial inocula and do not recapitulate the prolonged infections observed in some patients. Recently, our laboratory developed a murine model of chronic pulmonary infection that enabled the identification of virulence factors specifically required for long-term lung persistence. To investigate how A. baumannii adapts during chronic pulmonary infection, we performed an experimental evolution study using this model. This approach revealed an unexpected role for the archaic chaperone-usher (Csu) pili in A. baumannii pathogenesis. At early time points, Csu expression reduced bacterial burdens in both acute and chronic pneumonia models, an effect associated with enhanced host inflammatory responses. In contrast, at later stages of chronic infection, Csu promoted bacterial persistence, potentially by facilitating adhesion to pulmonary epithelial cells. These opposing effects were conserved across two distinct A. baumannii clinical isolates. We also found that Csu contributes to bacterial colonization in a catheter-associated urinary tract infection (CAUTI) model in a strain-dependent manner. Together, these findings reveal an infection-stage-dependent role for Csu in A. baumannii pathogenesis, demonstrating that a bacterial surface structure can impair early colonization while promoting long-term persistence.
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BibTeX
@misc{cavinato2026experimental,
title = {{Experimental evolution reveals temporally opposing roles for Csu pili during Acinetobacter baumannii respiratory infection}},
author = {L. Cavinato and C. D. Jackson-Litteken and E. M. Nawrocki and N. Dubey and C. Tai and M. Janet-Maitre and V. S. Cooper and C. L. Stallings and G. Di Venanzio and M. F. Feldman},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.29.762983},
url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762983v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Experimental evolution reveals temporally opposing roles for Csu pili during Acinetobacter baumannii respiratory infection
AU - L. Cavinato
AU - C. D. Jackson-Litteken
AU - E. M. Nawrocki
AU - N. Dubey
AU - C. Tai
AU - M. Janet-Maitre
AU - V. S. Cooper
AU - C. L. Stallings
AU - G. Di Venanzio
AU - M. F. Feldman
PY - 2026
DA - 2026/10/29
PB - bioRxiv
DO - 10.64898/2026.10.29.762983
UR - https://www.biorxiv.org/content/10.64898/2026.10.29.762983v1
AB - Multidrug-resistant (MDR) Acinetobacter baumannii is an opportunistic pathogen responsible for a wide range of infections, including ventilator-associated pneumonia, bloodstream infections, and urinary tract infections. Most studies investigating A. baumannii pulmonary pathogenesis rely on acute pneumonia models that use high bacterial inocula and do not recapitulate the prolonged infections observed in some patients. Recently, our laboratory developed a murine model of chronic pulmonary infection that enabled the identification of virulence factors specifically required for long-term lung persistence. To investigate how A. baumannii adapts during chronic pulmonary infection, we performed an experimental evolution study using this model. This approach revealed an unexpected role for the archaic chaperone-usher (Csu) pili in A. baumannii pathogenesis. At early time points, Csu expression reduced bacterial burdens in both acute and chronic pneumonia models, an effect associated with enhanced host inflammatory responses. In contrast, at later stages of chronic infection, Csu promoted bacterial persistence, potentially by facilitating adhesion to pulmonary epithelial cells. These opposing effects were conserved across two distinct A. baumannii clinical isolates. We also found that Csu contributes to bacterial colonization in a catheter-associated urinary tract infection (CAUTI) model in a strain-dependent manner. Together, these findings reveal an infection-stage-dependent role for Csu in A. baumannii pathogenesis, demonstrating that a bacterial surface structure can impair early colonization while promoting long-term persistence.
ER -