Fever-like temperature impacts on Staphylococcus aureus and Pseudomonas aeruginosa interaction, physiology, and virulence both in vitro and in vivo

SOLAR VENERO, E. C.; GALEANO, M. B.; LUQMAN, A.; RICARDI, M. M.; SERRAL, F.; FERNANDEZ DO PORTO, D.; ROBALDI, S. A.; ASHARI, B. A. Z.; MUNIF, T. H.; EGOBURO, D. E.; NEMIROVSKY, S.; ESCALANTE, J.; NISHIMURA, B.; RAMIREZ, M. S.; GÖTZ, F.; TRIBELLI, P. M.

BMC BIOLOGY

BIOMED CENTRAL LTD

Año: 2024 vol. 22

1741-7007

Background Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) cause a wide variety of bacterial infectionsand coinfections, showing a complex interaction that involves the production of different metabolites and metabolicchanges. Temperature is a key factor for bacterial survival and virulence and within the host, bacteria could beexposed to an increment in temperature during fever development. We analyzed the previously unexplored effectof fever-like temperatures (39 °C) on S. aureus USA300 and P. aeruginosa PAO1 microaerobic mono- and co-culturescompared with 37 °C, by using RNAseq and physiological assays including in vivo experiments.Results In general terms both temperature and co-culturing had a strong impact on both PA and SA with the exceptionof the temperature response of monocultured PA. We studied metabolic and virulence changes in both species.Altered metabolic features at 39 °C included arginine biosynthesis and the periplasmic glucose oxidation in S. aureusand P. aeruginosa monocultures respectively. When PA co-cultures were exposed at 39 °C, they upregulated ethanoloxidation-related genes along with an increment in organic acid accumulation. Regarding virulence factors, monoculturedSA showed an increase in the mRNA expression of the agr operon and hld, pmsα, and pmsβ genes at 39 °C.Supported by mRNA data, we performed physiological experiments and detected and increment in hemolysis,staphyloxantin production, and a decrease in biofilm formation at 39 °C. On the side of PA monocultures, we observedan increase in extracellular lipase and protease and biofilm formation at 39 °C along with a decrease in the motilityin correlation with changes observed at mRNA abundance. Additionally, we assessed host?pathogen interactionboth in vitro and in vivo. S. aureus monocultured at 39οCshowed a decrease in cellular invasion and an increasein IL-8?but not in IL-6?production by A549 cell line. PA also decreased its cellular invasion when monoculturedat 39 °C and did not induce any change in IL-8 or IL-6 production. PA strongly increased cellular invasion when coculturedat 37 and 39 °C. Finally, we observed increased lethality in mice intranasally inoculated with S. aureus monoculturespre-incubated at 39 °C and even higher levels when inoculated with co-cultures. The bacterial burden for P. aeruginosa was higher in liver when the mice were infected with co-cultures previously incubated at 39 °C comparingwith 37 °C.Conclusions Our results highlight a relevant change in the virulence of bacterial opportunistic pathogens exposedto fever-like temperatures in presence of competitors, opening new questions related to bacteria-bacteria and host?pathogen interactions and coevolution.