Adaptation to the ever-changing environmental conditions and survival outside the host is crucial for dissemination and transmission of pathogenic bacteria. Staphylococcus aureus may be spread from human carriers to diverse environments and survive outside the host for long periods of time. This capacity has been linked to reinfections in addition to new host colonisations. One of the main variables that bacteria need to face when leaving the host is a shift in temperature. However, the mechanisms governing cold adaptation during this transition remain poorly understood. In this study, we found that two paralogous RNA-thermoswitches controlled the production of cold-shock proteins CspB and CspC in S. aureus. We demonstrated that the cspB and cspC 5’UTRs adopt alternative RNA structures that shift from one another upon temperature changes. These RNA structures resembled the thermo-responsive elements recently described in E. coli and L. monocytogenes. One of the conformations facilitated mRNA translation at ambient temperatures (22ºC) while the other folded into a double stranded RNA structure at host-related temperatures (37ºC) that blocked the ribosome binding site (RBS). We found that the structural rearrangements depended on a long RNA hairpin that sequestered the anti-RBS sequence depending on the environmental temperature. At the same time, the remaining S. aureus CSP, CspA, recognised a UUUGUUU motif located in this long hairpin. Such interaction favoured the release of the anti-RBS sequence and, as a result, repressed the CspB and CspC production at 37ºC. In addition, when both RNA-thermoswitches were simultaneously deleted, S. aureus growth was inhibited at ambient temperatures. All in all, our [ndings highlight the importance of CspB/CspC thermoregulation when S. aureus transitions from the host to the environment.

Resumen del trabajo presentado en el World Microbe Forum. ASM-FEMS Congress, celebrado online del 20 al 24 de junio de 2021