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
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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
