Despite Antagonism in vitro, Pseudomonas aeruginosa Enhances Staphylococcus aureus Colonization in a Murine Lung Infection Model

Abstract

Staphylococcus aureus and Pseudomonas aeruginosa are prevalent lung pathogens in cystic fibrosis (CF). Whereas co-infection worsens the clinical outcome, prototypical strains are usually antagonistic in vitro. We sought to resolve the discrepancy between these in vitro and in vivo observations. In vitro, growth kinetics for co-cultures of coisolates from CF patients showed that not all P. aeruginosa strains affected S. aureus viability. On solid media, S. aureus slow-growing colonies were visualized around some P. aeruginosa strains whether or not S. aureus viability was reduced in liquid co-cultures. The S. aureus-P. aeruginosa interactions were then characterized in a mouse lung infection model. Lung homogenates were plated on selective media allowing colony counts of either bacterium. Overall, 35 P. aeruginosa and 10 S. aureus strains (clinical, reference, and mutant strains), for a total of 200 co-infections, were evaluated. We observed that S. aureus colonization of lung tissues was promoted by P. aeruginosa and even by strains showing antagonism in vitro. Promotion was proportional to the extent of P. aeruginosa colonization, but no correlation was found with the degree of myeloperoxidase quantification (as marker of inflammation) or with specific virulenceassociated factors using known mutant strains of S. aureus and P. aeruginosa. On the other hand, P. aeruginosa significantly increased the expression of two possible cell receptors for S. aureus, i.e., ICAM-1 and ITGA-5 (marker for integrin α 5 β 1) in lung tissue, while mono-infections by S. aureus did not. This study provides insights on polymicrobial interactions that may influence the progression of CF-associated pulmonary infections.

How Bacterial Adaptation to Cystic Fibrosis Environment Shapes Interactions Between Pseudomonas aeruginosa and Staphylococcus aureus

“…In addition, P. aeruginosa strains such as PA14 were shown to promote S. aureus colonization and maintenance in a murine lung infection model (Yadav et al, 2017;Millette et al, 2019). Similar results were obtained in the context of chronic wound co-infections (Pastar et al, 2013;DeLeon et al, 2014).…”

“…This hypothesis is supported by several studies showing the improved survival of S. aureus during non-human in vivo coinfections with P. aeruginosa, in comparison to in vitro cocultures. Yadav and colleagues demonstrated a higher proportion of S. aureus within an in vivo mixed-species biofilm in the presence of P. aeruginosa (Yadav et al, 2017;Millette et al, 2019).…”

Exoproteomics for Better Understanding Pseudomonas aeruginosa Virulence

“…Staphylococcus aureus and P. aeruginosa are commonly found together, causing serious acute and chronic infections, including pneumonia, urinary tract infections, and chronic wounds [111,112]. In CF patients, during the adolescence and early adulthood, P. aeruginosa replaces S. aureus but sometimes this latter is still detected in CF adults.…”

Bidirectional alterations in antibiotics susceptibility in Staphylococcus aureus—Pseudomonas aeruginosa dual-species biofilm

“…Current data suggests that bacterial pathogenicity is promoted during polymicrobial infections and recovery is delayed in comparison with monoculture infections 15 – 17 . Accordingly, interspecies interactions between S. aureus and P. aeruginosa within mixed biofilms attracted major attention in recent years including both in vitro 15 , 18 – 20 and in vivo studies 16 , 21 .…”