Which Microbial Factors Really are Important in Pseudomonas Aeruginosa Infections?

Abstract

Over the last two decades, tens of millions of dollars have been invested in understanding virulence in the human pathogen, Pseudomonas aeruginosa. However, the top 'hits' obtained in a recent TnSeq analysis aimed at identifying those genes that are conditionally essential for infection did not include most of the known virulence factors identified in these earlier studies. Instead, it seems that P. aeruginosa faces metabolic challenges in vivo, and unless it can overcome these, it fails to thrive and is cleared from the host. In this review, we look at the kinds of metabolic pathways that the pathogen seems to find essential, and comment on how this knowledge might be therapeutically exploited.

Chemical Genetics Reveals Environment-Specific Roles for Quorum Sensing Circuits in Pseudomonas aeruginosa

“…P. aeruginosa is highly adaptable to life in the varied environments found in these tissues (Brown et al, 2008). For example, the bacterium is able to feed on differing carbon sources (primarily amino acids in the CF airway and fatty acids in burn wounds) (Turner et al, 2014, Turner et al, 2015) and sense and respond to local changes in the concentration of essential nutrients (such as iron and phosphate), allowing it to adapt its mode of growth and virulence profile to establish either acute or chronic infections (Long et al, 2008, Markou and Apidianakis, 2014, Crousilles et al, 2015). Thus, it is perhaps unsurprising that P. aeruginosa possesses a sophisticated QS system that incorporates a large degree of environmental regulation (Wagner et al, 2003, Duan and Surette, 2007, Williams and Cámara, 2009).…”

Comparative analysis of the volatile metabolomes ofPseudomonas aeruginosaclinical isolates

“…A more thorough understanding of the P. aeruginosa metabolome could have significant positive impact on the clinical management of this pathogen [15, 16]. In particular, identifying the complete metabolic repertoire of clinical strains – or the clinical pan-metabolome – could shed light on mechanisms by which this organism establishes disease or evades therapy.…”

Multidrug Resistant Gram-Negative Bacteria in Community-Acquired Pneumonia

“…aeruginosa has intrinsic, adaptive and acquired mechanisms of resistance, the main ones including the presence of β-lactamases, alterations in membrane permeability due to the presence of ejection pumps, and mutations of transmembrane porins. Furthermore, the capacity to form biofilms (intricate, highly organized bacterial communities, embedded in a matrix composed of exopolysaccharides, DNA and proteins that is attached to a surface and hinders antimicrobial action) favors the persistence of P. aeruginosa and makes it more difficult to treat, due to the inherent protection that biofilms provide [8] (Table 1).…”