Biology subjects

Niggli, S.

Publications and source records attributed to Niggli, S..

3 recordsLinked to original sources

bioRxiv2021

Rapid and strain-specific resistance evolution of Staphylococcus aureus against inhibitory molecules secreted by Pseudomonas aeruginosa

Pseudomonas aeruginosa and Staphylococcus aureus frequently occur together in polymicrobial infections, and there is evidence that their interactions negatively affect disease outcome in patients. At the molecular level, interactions between the two bacterial species are well-described, with P. aeruginosa usually being the dominant species suppressing S. aureus through a variety of inhibitory molecules. However, in chronic infections the two species interact over prolonged periods of time, and S. aureus might be able to evolve resistance against inhibitory molecules deployed by P. aeruginosa. Here, we used experimental evolution to test this hypothesis by exposing three different S. aureus strains (Cowan I, 6850, JE2) to the growth-inhibitory supernatant of P. aeruginosa PAO1 over 30 days. Prior to evolution, we found that S. aureus strains were inhibited by secreted compounds regulatorily controlled by the PQS quorum-sensing system of P. aeruginosa. Following evolution, S. aureus strains were no longer inhibited: we observed that phenotypic adaptations were strain-specific and involved the up-regulation of virulence traits, such as staphyloxanthin production and the formation of small colony variants. At the genetic level, mutations in membrane transporters were the most frequent evolutionary targets. Our work indicates that adaptations of S. aureus to co-infecting pathogens occurs rapidly and involves both virulence traits and membrane transporters involved in drug resistance. Thus, pathogen evolution could promote species co-existence, complicate treatment options and therefore worsen disease outcome.

microbiology↗

bioRxiv2021

Single-cell imaging reveals that Staphylococcus aureus is highly competitive against Pseudomonas aeruginosa on surfaces

Pseudomonas aeruginosa and Staphylococcus aureus frequently occur together in polymicrobial infections, and their interactions can complicate disease progression as well as treatment options. While interactions between P. aeruginosa and S. aureus have been extensively described using planktonic batch cultures, little is known about whether and how individual cells interact with each other on solid substrates. This is important, because in infections, both species frequently colonize surfaces to form microcolony aggregates and biofilms. Here, we performed single-cell time-lapse fluorescence microscopy combined with automated image analysis to describe interactions between P. aeruginosa PAO1 with three different S. aureus strains (Cowan I, 6850, JE2) during microcolony growth on agarose surfaces. While P. aeruginosa is usually considered the dominant species, we found that the competitive balance tips in favor of S. aureus on surfaces. We observed that all S. aureus strains accelerated the onset of microcolony growth in competition with P. aeruginosa and significantly compromised P. aeruginosa growth prior to physical contact. These results suggest that S. aureus deploys mechanisms of both resource competition and interference competition via diffusible compounds. JE2 was the most competitive S. aureus strain, simply usurping P. aeruginosa microcolonies when coming into direct contact, while 6850 was the weakest competitor itself suppressed by P. aeruginosa. Moreover, P. aeruginosa reacted to the assault of S. aureus by showing increased directional growth and expedited expression of quorum sensing regulators controlling the synthesis of competitive traits. Altogether, our results reveal that quantitative single-cell live imaging has the potential to uncover microbial behaviors that cannot be predicted from batch culture studies, and thereby contribute to our understanding of interactions between pathogens that co-colonize host-associated surfaces during polymicrobial infections.

microbiology↗

bioRxiv2020

Impact of biotic and abiotic factors on competitive interactions between Pseudomonas aeruginosa and Staphylococcus aureus

Bacterial communities in the environment and in infections are typically diverse, yet we know little about the factors that determine interspecies interactions. Here, we apply concepts from ecological theory to understand how biotic and abiotic factors affect interaction patterns between the two opportunistic human pathogens Pseudomonas aeruginosa and Staphyloccocus aureus, which often co-occur in polymicrobial infections. Specifically, we conducted a series of short- and long-term competition experiments between P. aeruginosa PAO1 (as our reference strain) and three different S. aureus strains (Cowan I, 6850, JE2) at three starting frequencies and under three environmental (culturing) conditions. We found that the competitive ability of P. aeruginosa strongly depended on the strain background of S. aureus, whereby P. aeruginosa dominated against Cowan I and 6850, but not against JE2. In the latter case, both species could end up as winners depending on conditions. Specifically, we observed strong frequency-dependent fitness patterns, including positive frequency dependence, where P. aeruginosa could dominate JE2 only when common, but not when rare. Finally, changes in environmental (culturing) conditions fundamentally altered the competitive balance between the two species, in a way that P. aeruginosa dominance increased when moving from shaken to static environments. Altogether, our results highlight that ecological details can have profound effects on the competitive dynamics between co-infecting pathogens, and determine whether two species can co-exist or invade each others populations from rare. Moreover, our findings might parallel certain dynamics observed in chronic polymicrobial infections. ImportanceBacterial infections are frequently caused by more than one species and such polymicrobial infections are often considered more virulent and more difficult to treat than the respective monospecies infections. Pseudomonas aeruginosa and Staphyloccocus aureus are among the most important pathogens in polymicrobial infections and their co-occurrence is linked to worse disease outcome. There is great interest in understanding how these two species interact with each other and what the consequences for the host are. While previous studies have mainly looked at molecular mechanisms implicated in interactions between P. aeruginosa and S. aureus, here we show that ecological factors such as strain background, species frequency and environmental conditions are important elements determining population dynamics and species co-existence patterns. We propose that the uncovered principles may also play major roles in infections, and therefore proclaim that an integrative approach combining molecular and ecological aspects is required to fully understand polymicrobial infections.

microbiology↗