Iron-Mediated Control of Pseudomonas aeruginosa-Staphylococcus aureus Interactions in the Cystic Fibrosis Lung

Abstract

Communication is an important factor for bacterial survival, growth, and persistence. Much work has examined both inter-and intraspecies interactions and their effects on virulence. Now, researchers have begun to explore the ways in which host-modulated factors can impact bacterial interactions and subsequently affect patient outcomes. In this issue, two papers discuss how the host environment alters interactions between the pathogens Pseudomonas aeruginosa and Staphylococcus aureus, largely in the context of cystic fibrosis. MICROSCOPIC SOCIETY Just as macroscopic creatures must communicate in order to survive and thrive in the macroscopic world, so too do microorganisms "talk" with each other at the microscopic level. Instead of audio calls and visual cues, bacteria instead rely on the language of signaling molecules. As this method of cellular communication involves large numbers of cells coming to a "consensus" on subsequent group actions, researchers dubbed this behavior "quorum sensing." Classical quorum sensing has been largely focused on autoinduction, wherein a single species produces a signaling molecule unable to induce gene expression until the population grows to a threshold concentration. This phenomenon was first characterized in bioluminescence produced by Aliivibrio (formerly Vibrio) fischeri and has since been identified in a variety of clinically relevant human pathogens. More recent cell-cell communication research has revealed that other kinds of molecules, including metabolites and nutrients present in the growth environment, serve as cues that impact bacterial interactions (1-3). Additionally, interactions between different species have been found to occur in polymicrobial infections where they often form synergistic, virulence-enhancing relationships (4). MICRONUTRIENTS/MICROORGANISMSAs pathogenic bacteria prey upon their host as a living source of nourishment, it is not surprising that available nutrients in the host environment can have a major impact on microbial gene expression. It also follows, then, that such an important regulatory factor might also affect the ways in which bacteria interact within the host. Therefore, a key question is whether the in vitro systems primarily used to study microbial interactions provide relevant insights into the ways in which microbes interact in the host.This issue of the Journal of Bacteriology features two papers that explore the impact of host-provided nutrients further in the context of iron's ability to modulate Pseudomonas aeruginosa/Staphylococcus aureus interactions in the cystic fibrosis (CF) lung. Iron is a micronutrient vital for bacterial growth but relatively scarce in most infection sites, acting as a limiting factor (5). In contrast, iron levels have been found to be high in CF sputum and correlate negatively with patient outcomes (6). Additionally, pathogen lung colonization in CF patients displays a conserved pattern of succession, with S. aureus predominating early on before being displaced by P. aeruginosa (7). Although it has b...

A Continuous-Flow Model for in vitro Cultivation of Mixed Microbial Populations Associated With Cystic Fibrosis Airway Infections

“…Through viable cell counting and optical density measurements, we demonstrate that the abundance of each member of this microbial population remains unchanged over the course of 4 days and that a total carrying capacity can be reached and maintained within the culture vessel. By contrast, and in line with previous reports, when these species are co-cultured under batch conditions, PA rapidly outcompetes the other species (Machan et al, 1992; Duan et al, 2003; Hogan et al, 2004; Mashburn et al, 2005; McAlester et al, 2008; Cugini et al, 2010; Holcombe et al, 2010; Morales et al, 2010; Park et al, 2012; Korgaonkar et al, 2013; Baldan et al, 2014; Fugère et al, 2014; Rüger et al, 2014; Barnabie and Whiteley, 2015; Filkins et al, 2015; Nguyen et al, 2015; Zago et al, 2015; Nguyen and Oglesby-Sherrouse, 2016). Our in vitro model provides a defined and experimentally tractable system which can be used to dissect interspecies interactions and determine the long-term impact of co-cultivation on the physiology and gene expression profiles of CF-associated pathogens.…”

Iron at the Centre of Candida albicans Interactions

“…In addition, the lysis of bacterial or fungal cells may release iron into the environment that can act as a source for co-inhabitants. This phenomenon has been reported between co-habitants where Pseudomonas aeruginosa induces the lysis of S. aureus for iron (Mashburn et al, 2005 ; Barnabie and Whiteley, 2015 ; Nguyen et al, 2015 ). P. aeruginosa is another frequent co-isolate of C. albicans in the CF lung and reports indicate an antagonistic interaction between the fungus and bacterium in vitro .…”

Interactions between Pseudomonas aeruginosa and Staphylococcus aureus during co-cultivations and polymicrobial infections

“…Iron is an essential nutrient for most microbial pathogens and is increasingly appreciated as a critical mediator of CF lung disease (Bouvier 2016; Barnabie and Whiteley 2015; Cassat and Skaar 2013). Iron is limiting during infections due to sequestration by host proteins such as lactoferrin, transferrin, and hemoglobin (Otto, Verweij-van Vught, and MacLaren 1992; Nairz et al 2010).…”