Abstract
Trauma patients (TPs) are highly susceptible to infections, which often lead to sepsis. Among the numerous causative agents, Pseudomonas aeruginosa is especially important, as P. aeruginosa sepsis is often fatal. Understanding the mechanism of its pathogenesis in bloodstream infections is imperative; however, this mechanism has not been previously described. To examine the effect of trauma-induced changes in blood on the expression of P. aeruginosa genes, we grew strain UCBPP-PA14 (PA14) in blood samples from eight TPs and seven healthy volunteers (HVs). Compared with its growth in blood from HVs, the growth of PA14 in blood from TPs significantly altered the expression of 285 genes. Genes whose expression was significantly increased were related to carbon metabolism, especially malonate utilization and mannitol uptake, and efflux of heavy metals. Genes whose expression was significantly reduced included genes of the type VI secretion system, genes related to uptake and metabolism of amino acids, and genes related to biosynthesis and transport of the siderophores pyoverdine and pyochelin. These results suggest that during systemic infection in trauma patients, and to adapt to the trauma-induced changes in blood, P. aeruginosa adjusts positively and negatively the expression of numerous genes related to carbon metabolism and virulence, respectively. IMPORTANCE While a considerable body of knowledge regarding sepsis in trauma patients is available, the potential influence of trauma-induced changes in the blood of these patients on the pathogenesis of Pseudomonas aeruginosa is basically an unexplored area. Rather than using standard laboratory media, we grew P. aeruginosa in whole blood from either healthy volunteers or trauma patients. The specific changes in the P. aeruginosa transcriptome in response to growth in blood from trauma patients reflect the adaptation of this organism to the bloodstream environment. This knowledge is vital for understanding the strategies this pathogen uses to adapt and survive within the host during systemic infection. Such information will help researchers and clinicians to develop new approaches for treatment of sepsis caused by P. aeruginosa in trauma patients, especially in terms of recognizing the effects of specific therapies (e.g., iron, zinc, or mannitol) on the organism. Further, this information can most likely be extrapolated to all patients with P. aeruginosa septicemia.
Highlights
IMPORTANCE While a considerable body of knowledge regarding sepsis in trauma patients is available, the potential influence of trauma-induced changes in the blood of these patients on the pathogenesis of Pseudomonas aeruginosa is basically an unexplored area
We recently examined the effect of thermal injury on the expression of P. aeruginosa genes by comparing the level of gene expression when the organism was grown in whole blood from severely burned patients to that of the organisms grown in whole blood from healthy volunteers (HVs) [17]
Our study differs in four areas: (i) we used human blood as an ex vivo medium for growth of a laboratory strain of P. aeruginosa; (ii) rather than chronic infection, where biofilms are common, our model is of acute septicemia and examined adjustment of PA14 to planktonic growth within 4 h; (iii) we compared the effect of trauma-induced changes in the blood on the PA14 transcriptome to that when grown in blood from noninjured healthy individuals rather than to growth in a laboratory medium; and (iv) the exposure of PA14 to antibiotics was limited to any residual drug in the patients’ blood at the time of the blood draw
Summary
IMPORTANCE While a considerable body of knowledge regarding sepsis in trauma patients is available, the potential influence of trauma-induced changes in the blood of these patients on the pathogenesis of Pseudomonas aeruginosa is basically an unexplored area. As mannitol has been shown to induce the expression of these transporters in P. fluorescens [35], it was not surprising to find these genes upregulated in PA14 grown in the blood from our TPs, since mannitol is commonly used in the initial treatment of trauma patients to increase plasma osmolality and reduce intracranial pressure [36].
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