Human Pleural Fluid Elicits Pyruvate and Phenylalanine Metabolism in Acinetobacter baumannii to Enhance Cytotoxicity and Immune Evasion

Rodman, Nyah; Martinez, Jasmine; Fung, Sammie; Nakanouchi, Jun; Myers, Amber L.; Harris, Caitlin; Dang, Emily; Fernandez, Jennifer S.; Liu, Christine; Mendoza, Anthony; Jiménez, Verónica; Nikolaidis, Nikolas; Brennan, Catherine A.; Bonomo, Robert A.; Sieira, Rodrigo; Ramírez, María Soledad

doi:10.3389/fmicb.2019.01581

Cited by 33 publications

(51 citation statements)

References 87 publications

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“…These results are consistent with previous observations that the presence of HSA, a major component of CSF, in the culture medium is correlated with elevated expression of the citrate symporter in A. baumannii (22). Further supporting this data, exposure of A. baumannii to pleural fluid (PF), another HSA containing fluid, increases growth rate and survival of A. baumannii A118 (23).…”

Section: Csf Boosts Specific Metabolic Routes Without Increasing Growsupporting

confidence: 92%

“…Previous observations have shown that A. baumannii's response to different stimuli is dependent on each particular strain's degree of pathogenicity. Less pathogenic strains induced more changes in their phenotypic behavior to overcome the stressful environment and persist (23).…”

Section: Baumanniimentioning

confidence: 99%

“…Previous work showed that the presence of PF is correlated with modifications of the expression of more than 1100 A. baumannii genes including many virulence factors such as motility, biofilm formation, efflux, T6SS, fibrinolytic activity and capsule genes (18), and with an increase in cytotoxicity and immune evasion (23). HSA, a component of PF, might be responsible for all or part of these effects (18,20,22). The experiments showed in previous sections indicate that CSF produces effects similar to those observed with PF such as an increase in cytotoxicity and changes in expression of virulence genes.…”

Section: Hsa Plays a Role In A Baumannii Pathoadaptation When Exposementioning

confidence: 99%

“…This genetic plasticity, a consequence of its ability to acquire and integrate foreign DNA, gives A. baumannii's a tremendous metabolic versatility that permits the bacterium to adapt and persist in harsh conditions (2,(13)(14)(15)(16)(17). A. baumannii's success in causing numerous infections, where it gets in contact with different body components and fluids, must be the result of its capabilities to not only capture adequate genetic determinants but also regulate expression of the proper cell components (2,(13)(14)(15)(18)(19)(20). We have also previously documented that human serum albumin (HSA) and pleural fluid (HSA-containing fluid), affected A. baumannii behavior, triggering an adaptive response that modulates DNA uptake, cytotoxicity, immune evasion, stress responses and metabolism (18,(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal fluid (CSF) boosts metabolism and virulence expression factors in Acinetobacter baumannii

Martinez

Razo-Gutierrez

et al. 2020

Preprint

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In a recent report by the Centers for Disease Control and Prevention (CDC), multidrug resistant (MDR) Acinetobacter baumannii is a pathogen described as an "urgent threat". Infection with this bacterium manifests as different diseases such as community and nosocomial pneumonia, bloodstream infections, endocarditis, urinary tract, wound infections, burn infections, skin and soft tissue infections, and meningitis. In particular, nosocomial meningitis, a common complication of neurosurgery caused by extensively-drug resistant (XDR) A. baumannii, is extremely challenging to manage. Therefore, it is necessary to identify signals, such as exposure to cerebrospinal fluid (CSF), that trigger expression of virulence factors that are associated with the successful establishment and progress of this infection. While a hypervirulent A. baumannii strain did not show changes in its transcriptome when incubated in the presence of CSF, a low-virulence isolate showed significant differences in gene expression and phenotypic traits. Exposure to 4% CSF caused increased expression of virulence factors such as fimbriae, pilins, and iron chelators, and virulence as determined in various model systems. Furthermore, although CSF's presence did not enhance bacterial growth, it was associated with an increase of expression of genes encoding transcription, translation, and the ATP synthesis machinery. Experiments to identify the active CSF component pointed to human serum albumin (HSA).

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Section: Csf Boosts Specific Metabolic Routes Without Increasing Growsupporting

confidence: 92%

Section: Baumanniimentioning

confidence: 99%

Section: Hsa Plays a Role In A Baumannii Pathoadaptation When Exposementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cerebrospinal fluid (CSF) boosts metabolism and virulence expression factors in Acinetobacter baumannii

Martinez

Razo-Gutierrez

et al. 2020

Preprint

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“…Our previous work, which focused on the analysis of genes related to metabolic processes, showed that when A . baumannii encounters PF a surprisingly large number of genes related to metabolic processes were affected 19 . Due to changes in intracellular pyruvate and phenylalanine metabolism in the presence of PF, we observed that A .…”

Section: Introductionmentioning

confidence: 99%

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

Martinez

Fernandez

Liu

et al. 2019

Sci Rep

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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.

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Effect of Serum Albumin, a Component of Human Pleural Fluid, on Transcriptional and Phenotypic Changes on Acinetobacter baumannii A118

Pimentel

Tuttobene

et al. 2021

Curr Microbiol

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Acinetobacter baumannii is a multidrug resistant pathogen that causes numerous infections associated with high mortality rates. Exposure to human body fluids, such as human pleural fluid (HPF) and human serum, modulates gene expression in A. baumannii , leading to changes in its pathogenic behavior. Diverse degrees of effects at the transcriptional level were observed in susceptible and carbapenem-resistant strains. The transcriptional analysis of AB5075, a hyper-virulent and extensively drug-resistant strain showed changes in genes associated with quorum sensing, quorum quenching, fatty acids metabolism, and high-efficient iron uptake systems. In addition, the distinctive role of human serum albumin (HSA) as a critical component of HPF was evidenced. In the present work, we used model strain to analyze more deeply into the contribution of HSA in triggering A. baumannii’s response. By qRT-PCR analysis, changes in the expression level of genes associated with quorum sensing, biofilm formation, and phenylacetic acid pathway were observed. Phenotypic approaches confirmed the transcriptional response. HSA, a predominant component of HPF, can modulate the expression and behavior of genes not only in a hyper-virulent and extensively drug-resistant A. baumannii model, but also in other strains with a different degree of susceptibility and pathogenicity.

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Human Pleural Fluid Elicits Pyruvate and Phenylalanine Metabolism in Acinetobacter baumannii to Enhance Cytotoxicity and Immune Evasion

Cited by 33 publications

References 87 publications

Cerebrospinal fluid (CSF) boosts metabolism and virulence expression factors in Acinetobacter baumannii

Cerebrospinal fluid (CSF) boosts metabolism and virulence expression factors in Acinetobacter baumannii

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

Effect of Serum Albumin, a Component of Human Pleural Fluid, on Transcriptional and Phenotypic Changes on Acinetobacter baumannii A118

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