The serine-rich C-terminal tail of the Listeria monocytogenes secretion chaperone PrsA2 is critical for bacterial virulence and resistance to cell-wall active antibiotics
- 1Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
- 2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois, United States of America
Abstract
Protein intrinsically disordered regions (IDRs) are characterized by their lack of defined stable tertiary structure and are capable of adopting multiple conformations for functional activity. In chaperone proteins, these flexible regions are often sites of condition specific protein-protein interactions. In Listeria monocytogenes (Lm), PrsA2 is a peptidyl prolyl isomerase (PPIase) chaperone that promotes pathogenesis through the maturation of secreted proteins including the pore forming toxin, listeriolysin O (LLO). PrsA2 is composed of a PPIase domain and foldase domain that are critical for secreted protein function. In addition, PrsA2 contains an uncharacterized unstructured region, the carboxyl-terminal tail (C-tail) consisting of 10-amino acid residues rich in serine. Here, we demonstrate that the PrsA2 C-tail and its serine residues are critical for Lm bacterial virulence in a mouse septicemic model. We trace this virulence defect to a reduction in secreted LLO activity exhibited by Lm PrsA2 C-tail bacterial mutants. Further, we use biophysical and biochemical assays to establish that the PrsA2 C-tail is required for interacting with and folding the LLO toxin. We then characterize the PrsA2 C-tail as a critical factor in Lm survival under stress conditions and highlight its crucial role against cell-wall targeting antibiotics. PrsA homologs are well-conserved in Gram-positive bacteria, and this work characterizes the Lm PrsA2 C-tail, demonstrating its contribution to bacterial virulence, chaperone function, and secreted protein activity. Author summary: Compared to eukaryotes, unstructured protein regions within bacterial proteomes are much less abundant, yet they are increasingly recognized as important for protein function and regulation. In this study, we characterize an unstructured C-terminal region of the peptidyl-prolyl isomerase chaperone PrsA2 from the Gram-positive food-borne pathogen Listeria monocytogenes (Lm). We demonstrate that this PrsA2 C-tail region is a key determinant of Lm virulence, enabling the activity of the major pore-forming toxin listeriolysin O. In addition, the PrsA2 C-tail is critical for overcoming cell-wall targeting antibiotics. Since PrsA homologs are well conserved in Gram-positive bacteria, our findings may be widely applicable to several Gram-positive pathogens.
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BibTeX
@article{kumar2026serinerich,
title = {{The serine-rich C-terminal tail of the Listeria monocytogenes secretion chaperone PrsA2 is critical for bacterial virulence and resistance to cell-wall active antibiotics}},
author = {Allison H. Kumar and Charles Agbavor and Francis Alonzo 3rd and Laty A. Cahoon},
journal = {PLOS Pathogens},
year = {2026},
month = oct,
doi = {10.1371/journal.ppat.1014676},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014676},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The serine-rich C-terminal tail of the Listeria monocytogenes secretion chaperone PrsA2 is critical for bacterial virulence and resistance to cell-wall active antibiotics
AU - Allison H. Kumar
AU - Charles Agbavor
AU - Francis Alonzo 3rd
AU - Laty A. Cahoon
PY - 2026
DA - 2026/10/05
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014676
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014676
AB - Protein intrinsically disordered regions (IDRs) are characterized by their lack of defined stable tertiary structure and are capable of adopting multiple conformations for functional activity. In chaperone proteins, these flexible regions are often sites of condition specific protein-protein interactions. In Listeria monocytogenes (Lm), PrsA2 is a peptidyl prolyl isomerase (PPIase) chaperone that promotes pathogenesis through the maturation of secreted proteins including the pore forming toxin, listeriolysin O (LLO). PrsA2 is composed of a PPIase domain and foldase domain that are critical for secreted protein function. In addition, PrsA2 contains an uncharacterized unstructured region, the carboxyl-terminal tail (C-tail) consisting of 10-amino acid residues rich in serine. Here, we demonstrate that the PrsA2 C-tail and its serine residues are critical for Lm bacterial virulence in a mouse septicemic model. We trace this virulence defect to a reduction in secreted LLO activity exhibited by Lm PrsA2 C-tail bacterial mutants. Further, we use biophysical and biochemical assays to establish that the PrsA2 C-tail is required for interacting with and folding the LLO toxin. We then characterize the PrsA2 C-tail as a critical factor in Lm survival under stress conditions and highlight its crucial role against cell-wall targeting antibiotics. PrsA homologs are well-conserved in Gram-positive bacteria, and this work characterizes the Lm PrsA2 C-tail, demonstrating its contribution to bacterial virulence, chaperone function, and secreted protein activity. Author summary: Compared to eukaryotes, unstructured protein regions within bacterial proteomes are much less abundant, yet they are increasingly recognized as important for protein function and regulation. In this study, we characterize an unstructured C-terminal region of the peptidyl-prolyl isomerase chaperone PrsA2 from the Gram-positive food-borne pathogen Listeria monocytogenes (Lm). We demonstrate that this PrsA2 C-tail region is a key determinant of Lm virulence, enabling the activity of the major pore-forming toxin listeriolysin O. In addition, the PrsA2 C-tail is critical for overcoming cell-wall targeting antibiotics. Since PrsA homologs are well conserved in Gram-positive bacteria, our findings may be widely applicable to several Gram-positive pathogens.
SN - 1553-7374
ER -