Strain-Specific Pseudomonas aeruginosa Conditioned Media Induce Distinct miRNA-Associated Regulatory Responses in Lung Epithelial Cells
- 1Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno d’Alcontres 31, 98166 Messina, Italy
- 2Institute of Translational Pharmacology (IFT), National Research Council of Italy (CNR), Via La Malfa 153, 90146 Palermo, Italy
Abstract
Pseudomonas aeruginosa exhibits substantial strain-dependent phenotypic heterogeneity, but whether differences in its extracellular milieu translate into distinct host regulatory responses remains poorly understood. This study investigated miRNA-associated responses in A549 lung epithelial cells exposed to conditioned media (CM) from P. aeruginosa ATCC 27853 and two clinical isolates, Pr and Pc. Phenazine-related gene expression was characterized, sub-cytotoxic CM concentrations were selected by XTT assay, cellular morphology, miRNA and mRNA expression, IL-8 secretion, and apoptosis were evaluated. Pc showed significantly higher expression of both phzM and phzS, consistent with its pyocyanin-producing phenotype. Pc-CM induced pronounced morphological remodelling and early hsa-miR-34a-5p upregulation, followed by BCL2 downregulation, marked CASP7 induction, and increased early apoptosis. Conversely, Pr-CM significantly reduced hsa-miR-146a-5p expression, followed by selective CXCL8 induction and enhanced IL-8 secretion. ATCC-CM induced transcriptional changes, including BCL2 downregulation, without reproducing either clinical isolate-associated response profile. These findings reveal divergent epithelial responses to strain-specific extracellular environments, with Pc-CM predominantly associated with apoptosis-related changes and Pr-CM with inflammatory signalling. These findings suggest that miRNA modulation may represent a molecular interface linking strain-dependent extracellular heterogeneity to distinct host–cell responses.
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BibTeX
@article{franco2026strainspecific,
title = {{Strain-Specific Pseudomonas aeruginosa Conditioned Media Induce Distinct miRNA-Associated Regulatory Responses in Lung Epithelial Cells}},
author = {Domenico Franco and Salvatore Papasergi and Caterina Cascio and Maria Ferraro and Laura M. De Plano},
journal = {Biomolecules},
year = {2026},
month = nov,
doi = {10.3390/biom16111624},
url = {https://www.mdpi.com/2218-273X/16/11/1624},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Strain-Specific Pseudomonas aeruginosa Conditioned Media Induce Distinct miRNA-Associated Regulatory Responses in Lung Epithelial Cells
AU - Domenico Franco
AU - Salvatore Papasergi
AU - Caterina Cascio
AU - Maria Ferraro
AU - Laura M. De Plano
PY - 2026
DA - 2026/11/07
JO - Biomolecules
DO - 10.3390/biom16111624
UR - https://www.mdpi.com/2218-273X/16/11/1624
AB - Pseudomonas aeruginosa exhibits substantial strain-dependent phenotypic heterogeneity, but whether differences in its extracellular milieu translate into distinct host regulatory responses remains poorly understood. This study investigated miRNA-associated responses in A549 lung epithelial cells exposed to conditioned media (CM) from P. aeruginosa ATCC 27853 and two clinical isolates, Pr and Pc. Phenazine-related gene expression was characterized, sub-cytotoxic CM concentrations were selected by XTT assay, cellular morphology, miRNA and mRNA expression, IL-8 secretion, and apoptosis were evaluated. Pc showed significantly higher expression of both phzM and phzS, consistent with its pyocyanin-producing phenotype. Pc-CM induced pronounced morphological remodelling and early hsa-miR-34a-5p upregulation, followed by BCL2 downregulation, marked CASP7 induction, and increased early apoptosis. Conversely, Pr-CM significantly reduced hsa-miR-146a-5p expression, followed by selective CXCL8 induction and enhanced IL-8 secretion. ATCC-CM induced transcriptional changes, including BCL2 downregulation, without reproducing either clinical isolate-associated response profile. These findings reveal divergent epithelial responses to strain-specific extracellular environments, with Pc-CM predominantly associated with apoptosis-related changes and Pr-CM with inflammatory signalling. These findings suggest that miRNA modulation may represent a molecular interface linking strain-dependent extracellular heterogeneity to distinct host–cell responses.
SN - 2218-273X
ER -