Towards understanding Pseudomonas aeruginosa burn wound infections by profiling gene expression

Abstract

Pseudomonas aeruginosa is a key opportunistic pathogen causing severe acute and chronic nosocomial infections in immunocompromised or catheterized patients. It is prevalent in burn wound infections and it is generally multi-drug resistant. Understanding the genetic programs underlying infection is essential to develop highly needed new strategies for prevention and therapy. This work reviews expression profiling efforts conducted worldwide towards gaining insights into pathogenesis by P. aeruginosa, in particular in burn wounds. Work on various infection models, including the burned mouse model, has identified several direct virulence factors and elucidated their mode of action. In vivo gene expression experiments using In vivo Expression Technology (IVET) ascertained distinct regulatory circuits and traits that have helped explain P. aeruginosa s success as a general pathogen. The sequencing of the whole genome from a number of P. aeruginosa strains and the construction of genome-wide microarrays have paved the road to the several insightful studies on the (interacting) traits underlying infection. A series of in vitro and initial in vivo gene expression studies revealed specific traits pivotal for infection, such as quorum sensing systems, iron acquisition and oxidative stress responses, and toxin production among others. The data sets obtained from global transcriptional profiling provide insights that will be essential for the development of new targets and options for prevention and intervention.

Flagellum-Mediated Biofilm Defense Mechanisms of Pseudomonas aeruginosa against Host-Derived Lactoferrin

“…Biofilm communities of P. aeruginosa have been observed in chronic wounds and burn wounds, where they are a leading cause of bacterial sepsis and mortality (5,7,50). Additionally, P. aeruginosa will form biofilms on implanted medical devices including prostheses, catheters, and central venous lines, among others (51).…”

“…Schaber and colleagues (50) demonstrated the formation of biofilms on a mouse burn model after just 8 h postinoculation. In a 3-year study in Poland, P. aeruginosa was the most abundant organism isolated from burn wounds (5). Additionally, P. aeruginosa biofilm presence in chronic wounds is a likely culprit for the longevity of these infections by keeping the wound in a chronic state of inflammation (7,31).…”

Bacterial Quorum Sensing: Its Role in Virulence and Possibilities for Its Control

“…This infection leads to declined pulmonary function and increased mortality. P. aeruginosa also causes acute infections in people with compromised epithelial barriers; a common trait among patients with severe burns or tracheal intubation and mechanical ventilation (Bielecki et al 2008). In both scenarios, P. aeruginosa uses QS to collectively produce a suite of virulence factors that contribute to its disease-causing ability.…”

Cif Is Negatively Regulated by the TetR Family Repressor CifR

“…Disease in humans shows a relative lack of tropism, as infections caused by P. aeruginosa can be found in tissues as varied as the skin, ocular epithelia, and the lung (3,28,31). This pathogenic plasticity is largely due to the presence of a multiplicity of virulence factors which allow for colonization and the establishment of infection (1).…”