In vivo bacterial cooperation in cystic fibrosis: exposure to Stenotrophomonas maltophilia affects Pseudomonas aeruginosa virulence in murine model of acute lung infection.

Introduction Several studies suggested that a complex microbiota resides in the lungs of cystic fibrosis (CF) patients, thus indicating that pathogenic processes in CF airways might be due to polymicrobial interactions. Stenotrophomonas maltophilia, whose pathogenetic role in CF is not yet clear, is often co-isolated from CF lungs with Pseudomonas aeruginosa. Our hypothesis is that S. maltophilia can modulate, directly or indirectly, P. aeruginosa virulence, thus contributing to the respiratory function decline in CF patients. In this study, we evaluated the in vivo effects exerted by S. maltophilia on P. aeruginosa virulence. Materials and Methods P. aeruginosa DIN2 and S. maltophilia DIN3 strains, co-isolated from the lung of a chronically colonized CF patient, were tested. The in vivo effects of S. maltophilia on P. aeruginosa virulence were assessed in C57BL/6N mice following intratracheal exposure to each strain alone and in combination. Changes in mice weight, quantitative lung bacteriology, lung histology, and pulmonary interleukines were evaluated over 24h. Results Infection caused by P. aeruginosa and S. maltophilia, alone or in combination, provoked a reduction of mice body weight compared to controls, although not statistically significant. Macroscopic score index revealed that DIN2+DIN3 co-infection caused a higher damage than DIN3 alone, but comparable to DIN2 alone, as confirmed by mortality rate. When tested alone or in co-culture, P. aeruginosa exhibited longer pulmonary persistence than S. maltophilia alone did. Histological analysis revealed that alveolar involvement and intraluminar infiltrate were higher in the lungs of co-infected mice, although these differences were not statistically significant. Infection caused by DIN2 alone induced higher pulmonary levels of interleukines, compared to mixed DIN3+DIN2 infection. Conclusions Overall, our results showed that in vivo S. maltophilia is able to modulate P. aeruginosa virulence, thus suggesting that studying bacterial interactions should be considered in evaluating CF disease progression. Further studies are warranted to confirm our findings, to identify the underlying mechanisms, and to evaluate the impact of these interactions on the management of CF patients.