Beyond extremophiles: conserved molecular toolkits enable the resilience of human-associated microbes to Martian stressors

The inevitable introduction of human-associated microbes on Mars poses significant planetary protection risks, yet the survival potential of non-extremophiles under surface conditions remains ill-defined. We evaluated the resilience of three common gut bacteria— Enterococcus faecalis , Serratia liquefaciens , a nd Escherichia coli —under simulated Martian stressors including low pressure, CO₂-rich atmosphere, and perchlorate exposure, applied individually and in combination. Growth assays revealed a distinct tolerance hierarchy, with E. faecalis exhibiting the highest robustness, followed by E. coli and S. liquefaciens . Notably, combined stressors produced predominantly antagonistic effects across all three strains, indicating interactions that single-stressor assays may fail to capture. Transcriptomic profiling of E. faecalis under combined stress revealed a coordinated adaptive response involving conserved stress-response mechanisms rather than lineage-specific innovations. A concurrent potential shift toward enhanced surface adhesion and efflux activity, alongside suppression of acute virulence factors, raises biosafety concerns for crewed missions. Collectively, these results support a continuum model of microbial stress tolerance, in which persistence under extraterrestrial conditions does not require specialized extremophilic traits but can emerge from dynamic regulation of conserved systems, broadening the range of microorganisms relevant to forward-contamination risk.