Human pleural fluid triggers global changes in the transcriptional landscape of Acinetobacter baumannii as an adaptive response to stress

Jasmine Martinez,Maria Soledad Ramirez,Carolina Lopez,Rodrigo Sieira,Lisandro J Gonzalez,Robert A Bonomo,Marcelo E Tolmasky,Marisel R Tuttobene,Krisztina M Papp-Wallace,Parvin Shahrestani,Robert Courville,Nyah Rodman,Christine Liu,Jun Nakanouchi,Jennifer S Fernandez,Amparo Hoard,Alejandro J Vila,Anthony Mendoza

doi:10.1038/s41598-019-53847-2

Abstract

Acinetobacter baumannii is a feared, drug-resistant pathogen, characterized by its ability to resist extreme environmental and nutrient-deprived conditions. Previously, we showed that human serum albumin (HSA) can increase foreign DNA acquisition specifically and alter the expression of genes associated with pathogenicity. Moreover, in a recent genome-wide transcriptomic study, we observed that pleural fluid (PF), an HSA-containing fluid, increases DNA acquisition, can modulate cytotoxicity, and control immune responses by eliciting changes in the A. baumannii metabolic profile. In the present work, using more stringent criteria and focusing on the analysis of genes related to pathogenicity and response to stress, we analyzed our previous RNA-seq data and performed phenotypic assays to further explore the impact of PF on A. baumannii’s microbial behavior and the strategies used to overcome environmental stress. We observed that PF triggered differential expression of genes associated with motility, efflux pumps, antimicrobial resistance, biofilm formation, two-component systems (TCSs), capsule synthesis, osmotic stress, and DNA-damage response, among other categories. Phenotypic assays of A. baumannii A118 and two other clinical A. baumannii strains, revealed differences in their responses to PF in motility, biofilm formation, antibiotic susceptibility, osmotic stress, and outer membrane vesicle (OMV) production, suggesting that these changes are strain specific. We conclude that A. baumannii’s pathoadaptive responses is induced by HSA-containing fluids and must be part of this bacterium armamentarium to persist in hostile environments.

Highlights

Acinetobacter baumannii is a multi-drug-resistant (MDR) pathogen accounting for high mortality rates in immunocompromised patients
In this study, taking advantage of our existing RNA-seq data and with a complementary goal to our previous work[19], we further explore the impact of pleural fluid (PF) exposure on A. baumannii gene expression and on the behavior of traits involved in its pathogenicity
Strains A42 and AB5075 showed an increase in number of outer membrane vesicle (OMV) released in the presence of PF. These results strongly suggest that OMV release may be another strategy used by A. baumannii to respond to the stress caused by the presence of PF (See Supplementary Table S4)

Summary

Introduction

Acinetobacter baumannii is a multi-drug-resistant (MDR) pathogen accounting for high mortality rates in immunocompromised patients. Jacobs et al showed that a culture of A. baumannii in the presence of human serum up-regulates the expression of genes coding for iron acquisition, drug efflux pumps, epithelial cell adherence and DNA uptake[15]. Further supporting this observation, human serum albumin (HSA) was shown to trigger the differential expression of a number of key genes involved in the survival and persistence of A. baumannii[17]. Due to changes in intracellular pyruvate and phenylalanine metabolism in the presence of PF, we observed that A. baumannii cytotoxicity and immune evasion were enhanced This finding illustrates the key role played by bacterial metabolism in the pathophysiology of this bacterium during respiratory infections[19]. In this study, taking advantage of our existing RNA-seq data and with a complementary goal to our previous work[19], we further explore the impact of PF exposure on A. baumannii gene expression and on the behavior of traits involved in its pathogenicity

Methods

Results

Conclusion