Transcriptome Analysis of Pseudomonas aeruginosa Cultured in Human Burn Wound Exudates

Abstract

Pseudomonas aeruginosa is a severe opportunistic pathogen and is one of the major causes of hard to treat burn wound infections. Herein we have used an RNA-seq transcriptomic approach to study the behavior of P. aeruginosa PAO1 growing directly on human burn wound exudate. A chemical analysis of compounds used by this bacterium, coupled with kinetics expression of central genes has allowed us to obtain a global view of P. aeruginosa physiological and metabolic changes occurring while growing on human burn wound exudate. In addition to the numerous virulence factors and their secretion systems, we have found that all iron acquisition mechanisms were overexpressed. Deletion and complementation with pyoverdine demonstrated that iron availability was a major limiting factor in burn wound exudate. The quorum sensing systems, known to be important for the virulence of P. aeruginosa, although moderately induced, were activated even at low cell density. Analysis of bacterial metabolism emphasized importance of lactate, lipid and collagen degradation pathways. Overall, this work allowed to designate, for the first time, a global view of P. aeruginosa characteristics while growing in human burn wound exudate and highlight the possible therapeutic approaches to combat P. aeruginosa burn wound infections.

Distinct Tissue Damage and Microbial Cues Drive Neutrophil and Macrophage Recruitment to Thermal Injury

“…Both damage and microbial cues recruit innate phagocytes, and the balance of this inflammation can determine clinical outcome (Church et al, 2006;Ipaktchi et al, 2006). We identified IL-6 as a key signal that controls neutrophil responses to sterile thermal injury but is not necessary for neutrophil recruitment to wounds infected with P. aeruginosa, a common pathogen found in human burn injuries (Gonzalez et al, 2018). Our findings highlight context-dependent signals that differentially regulate neutrophil and macrophage responses that impact tissue repair.…”

Forging New Antibiotic Combinations under Iron-Limiting Conditions

“…Thus, repurposing iron chelators as antibiotic adjuvants may increase the expression of iron uptake pathways that can then be exploited to deliver antibacterial compounds. Both P. aeruginosa and A. baumannii express pyoverdine receptors FpvA and FpvB, which are highly upregulated under iron-limited conditions (6,7). TS hijacks these pyoverdine receptors to enter the cell, as mutants lacking both receptors are resistant.…”

Forging new antibiotic combinations under iron-limiting conditions

“…Thus, repurposing iron chelators as antibiotic adjuvants may increase expression of iron-uptake pathways that can then be exploited to deliver antibacterial compounds. Both P. aeruginosa and A. baumannii express pyoverdine receptors FpvA and FpvB, which are highly upregulated under iron-limited conditions (6, 7). TS hijacks these pyoverdine receptors to enter the cell, as mutants lacking both receptors are resistant.…”

“…To overcome iron limitation, P. aeruginosa produces the iron-scavenging siderophores pyochelin and pyoverdine that bind iron with low and high affinity, respectively (3–5). Pyoverdine and its outer membrane receptors, FpvA and FpvB, are highly expressed in low-iron conditions (3, 6, 7). Pyoverdine has such a high binding affinity (10 32 M −1 ) for iron that it can strip it from transferrin, a mammalian protein responsible for sequestering iron to impede bacterial growth (8–11).…”