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 co-isolates 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 virulence-associated 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 α5β1) 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.
Highlights
Cystic fibrosis (CF) is the most common recessive genetic disorder leading to chronic pulmonary infections, gastrointestinal disorders, diabetes, and other health complications
We observed a similar antagonism by P. aeruginosa on S. aureus for the cystic fibrosis (CF) patient co-isolates PAC6B and CF6B-L, PAC39A and CF39AL, and PAC112A and CF112A-L, respectively (Supplementary Figure S1), the reduction of S. aureus CFU/mL counts at 48 h was less than that observed for CF07-L co-cultured with PA14 (i.e., 1.9, 2.1, and 3.6 log10, respectively)
A different scenario was observed with the CF patient co-isolates P. aeruginosa PAC22A and S. aureus CF22A-L, where no effect on S. aureus viability was observed (Figure 1G) slow-growing colonies of S. aureus appeared around the P. aeruginosa central colony (Figure 1H)
Summary
Cystic fibrosis (CF) is the most common recessive genetic disorder leading to chronic pulmonary infections, gastrointestinal disorders, diabetes, and other health complications. P. aeruginosa Enhances S. aureus Colonization in vivo conductance regulator (CFTR), which is a membrane protein and chloride channel, causes abnormally thick and viscous mucus production in the lung mucosa (Ratjen, 2009; Kreda et al, 2012). This defect affects muco-ciliary clearance, reduces bacterial killing via an impaired HCO3 excretion, and supports bacterial growth (Castellani and Assael, 2017). The establishment of this feedback loop results in frequent exacerbations and increasingly reduced lung functions, which eventually lead to death (Lyczak et al, 2002)
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