Staphylococcus aureus Serves as an Iron Source for Pseudomonas aeruginosa during In Vivo Coculture

Abstract

Pseudomonas aeruginosa is a gram-negative opportunistic human pathogen often infecting the lungs of individuals with the heritable disease cystic fibrosis and the peritoneum of individuals undergoing continuous ambulatory peritoneal dialysis. Often these infections are not caused by colonization with P. aeruginosa alone but instead by a consortium of pathogenic bacteria. Little is known about growth and persistence of P. aeruginosa in vivo, and less is known about the impact of coinfecting bacteria on P. aeruginosa pathogenesis and physiology. In this study, a rat dialysis membrane peritoneal model was used to evaluate the in vivo transcriptome of P. aeruginosa in monoculture and in coculture with Staphylococcus aureus. Monoculture results indicate that approximately 5% of all P. aeruginosa genes are differentially regulated during growth in vivo compared to in vitro controls. Included in this analysis are genes important for iron acquisition and growth in low-oxygen environments. The presence of S. aureus caused decreased transcription of P. aeruginosa ironregulated genes during in vivo coculture, indicating that the presence of S. aureus increases usable iron for P. aeruginosa in this environment. We propose a model where P. aeruginosa lyses S. aureus and uses released iron for growth in low-iron environments.Pseudomonas aeruginosa is a gram-negative opportunistic human pathogen commonly found in water and soil. P. aeruginosa causes a number of chronic and acute infections and is noted for its inherent resistance to many clinically relevant antibiotics. Two of the most common infections caused by P. aeruginosa are chronic colonization of the lungs of individuals with the genetic disease cystic fibrosis (CF) (19) and peritonitis in individuals undergoing continuous ambulatory peritoneal dialysis (CAPD) (25). The lungs of CF patients are commonly colonized before the age of 8, and most individuals maintain these infections throughout their lifetimes. High infection rates are also associated with CAPD, which is often used to treat end-stage renal disease.P. aeruginosa physiology and gene expression during in vivo growth is largely unknown. Using in vivo expression technology (IVET), Wang et al. identified 19 P. aeruginosa genes inducible during growth in a neutropenic mouse (40). Although that study identified several new genes important for virulence in P. aeruginosa, it did not provide a comprehensive analysis of in vivo gene expression. Two recent studies using Pasteurella multocida and Borrelia burgdorferi have provided a more comprehensive view of in vivo bacterial gene expression by using DNA microarrays (3, 4, 33). These studies illustrate that a significant number of genes (2 to 8% of all the genes in the genomes) are differentially regulated in vivo, suggesting that the in vivo environment is distinct from normal in vitro culture conditions.Although evaluation of the transcriptomes of in vivo-grown bacteria provides a snapshot of transcription under monoculture growth conditions, it is clear that many in...

Pseudomonas aeruginosa eradicates Staphylococcus aureus by manipulating the host immunity

“…We should, however, keep in mind that, in addition to sPLA2-IIA, other processes might also potentially contribute to the age-dependent decrease of SA loads in CF airways [33][34][35][36] . Thus, sPLA2-IIA can be considered as a part of complex process involved in the selective elimination of SA from CF airways.…”

“…In most cases, SA colonizes airways of young CF patients, while PA predominates in those of adult patients [10][11][12] . A number of hypotheses have been proposed to explain the elimination of SA from airways of CF patients [33][34][35][36] . However, the pertinence of these hypotheses remained elusive, probably due to the complexity of CF infection and the lack of relevant animal models.…”

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

“…Some of these bacteriocins, such as the Pseudomonas pyocin, share the same receptors as siderophores (Denayer et al, 2007;Elfarash et al, 2014) and therefore interfere with iron acquisition of their target host. It has also been demonstrated that P. aeruginosa can lyse Staphylococcus aureus using PqsA, a coenzyme ligase, to gain access to internalized iron (Mashburn et al, 2005). Staphylococcus aureus, however, can also compete with P. aeruginosa for free iron (Mashburn et al, 2005;Harrison et al, 2008).…”

Pseudomonas Quinolone Signal Affects Membrane Vesicle Production in not only Gram-Negative but also Gram-Positive Bacteria

“…In addition, PQS positively regulates several virulence factors in P. aeruginosa (6), and virulence factors under its control have lytic activities against Gram-positive bacteria (23,30). Thus, PQS has a role in competing with other bacteria in polymicrobial communities.…”