During bacteremia, Pseudomonas aeruginosa PAO1 adapts by altering the expression of numerous virulence genes including those involved in quorum sensing.

Kellsie L Beasley,Nyaradzo Dzvova,Moamen M Elmassry,Abdul N Hamood,Shane A Cristy,Jane A Colmer-Hamood,Roy Martin Roop

doi:10.1371/journal.pone.0240351

Kellsie L Beasley, Nyaradzo Dzvova + Show 5 more

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https://doi.org/10.1371/journal.pone.0240351

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Abstract

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that produces numerous virulence factors and causes serious infections in trauma patients and patients with severe burns. We previously showed that the growth of P. aeruginosa in blood from severely burned or trauma patients altered the expression of numerous genes. However, the specific influence of whole blood from healthy volunteers on P. aeruginosa gene expression is not known. Transcriptome analysis of P. aeruginosa grown for 4 h in blood from healthy volunteers compared to that when grown in laboratory medium revealed that the expression of 1085 genes was significantly altered. Quorum sensing (QS), QS-related, and pyochelin synthesis genes were downregulated, while genes of the type III secretion system and those for pyoverdine synthesis were upregulated. The observed effect on the QS and QS-related genes was shown to reside within serum fraction: growth of PAO1 in the presence of 10% human serum from healthy volunteers significantly reduced the expression of QS and QS-regulated genes at 2 and 4 h of growth but significantly enhanced their expression at 8 h. Additionally, the production of QS-regulated virulence factors, including LasA and pyocyanin, was also influenced by the presence of human serum. Serum fractionation experiments revealed that part of the observed effect resides within the serum fraction containing <10-kDa proteins. Growth in serum reduced the production of many PAO1 outer membrane proteins but enhanced the production of others including OprF, a protein previously shown to play a role in the regulation of QS gene expression. These results suggest that factor(s) within human serum: 1) impact P. aeruginosa pathogenesis by influencing the expression of different genes; 2) differentially regulate the expression of QS and QS-related genes in a growth phase- or time-dependent mechanism; and 3) manipulate the production of P. aeruginosa outer membrane proteins.

Highlights

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes serious infections in immunocompromised hosts, including severely burned patients and HIV patients [1,2,3]
Using qRT-PCR to assess gene expression, we found that, as seen with its growth in whole blood, the relative expression of lasR and lasI in PAO1 grown in LBB supplemented with 10% human serum (LBBS) compared to Luria-Bertani broth (LBB) was reduced at early time points of growth (2 and 4 h) (Fig 7A)
We previously showed that, compared with its growth in whole blood from healthy volunteers (WBHVs), the growth of P. aeruginosa in whole blood (WB) from severely burned patients significantly enhanced the expression of TTSS, pyochelin, and pyoverdine genes compared to the level of their expression in WBHV, but significantly repressed the expression of quorum sensing (QS) and QS-related virulence genes [37]

Summary

Introduction

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes serious infections in immunocompromised hosts, including severely burned patients and HIV patients [1,2,3]. It grows ubiquitously in the environment and transiently colonizes the surface of the host’s body, P. aeruginosa colonizes nearly any site where there is a break in the host’s defenses (such as a surgical wound or burn infection) [1,4]. Once established within the wound environment, P. aeruginosa translocates into the bloodstream, leading to sepsis and septic shock [5]. P. aeruginosa pathogenesis at different infection sites has been extensively analyzed, little is known regarding the pathogenesis of P. aeruginosa upon its entry into the bloodstream

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