The diminishing effectiveness of traditional antibiotics necessitates alternative treatment strategies. One promising novel approach is the use of pathoblockers. These compounds inhibit bacterial virulence factors without effecting bacterial growth. In this study, we explore the use of a compound that interferes with quorum sensing of Pseudomonas aeruginosa, a pathogen that commonly causes severe lung infections. The tested compound blocks the Pseudomonas quinolone signal and thereby downregulates virulence factors including toxins with anti-prokaryotic activity¹. We hypothesize that the pathoblocker acting on P. aeruginosa may have effects on bacterial interactions with other coexisting pathogens.

In order to test this hypothesis, we performed spent media and cocultivation experiments of P. aeruginosa and a panel of microbes, which are commonly isolated from patients (Staphylococcus aureus, Serratia marcescens, Escherichia coli), in presence and absence of the compound. Furthermore, we used qPCR and RNA sequencing to elucidate the underlying mechanisms of pathoblocker treatment. Our results demonstrate a significant impact of the pathoblocker on P. aeruginosas' ability to reduce the number of living cells of S. aureus and E. coli in spent media. Additionally, the treatment leads to increased survival of S. aureus during cocultivation with P. aeruginosa.

In conclusion, this study highlights the importance of bacterial interactions in the context of drug development.

⁽¹⁾ Hamed, M. M.; Abdelsamie, A. S.; Rox, K.; Schütz, C.; Kany, A. M.; Röhrig, T.; Schmelz, S.; Blankenfeldt, W.; Arce-Rodriguez, A.; Borrero-de Acuña, J. M.; Jahn, D.; Rademacher, J.; Ringshausen, F. C.; Cramer, N.; Tümmler, B.; Hirsch, A. K. H.; Hartmann, R. W.; Empting, M. Towards Translation of PqsR Inverse Agonists: From In Vitro Efficacy Optimization to In Vivo Proof-of-Principle. Adv. Sci. 2023, 10 (5), 2204443. https://doi.org/10.1002/advs.202204443.