genetic analysis of carbon catabolic repression through the study of CrcZ pseudo-revertants shows that Crc-mediated metabolic robustness is needed for proficient bacterial virulence and antibiotic resistance.

Hfq and Crc regulate carbon catabolic repression at the post-transcriptional level. work has shown that Hfq binds the target RNAs and Crc stabilizes the complex. A third element in the regulation is the small RNA CrcZ, which sequesters the Crc-Hfq complex under no catabolic repression conditions, allowing the translation of the target mRNAs. A Δ mutant was generated and presented fitness defects and alterations in its virulence potential and antibiotic resistance. Eight pseudo-revertants that present different degrees of fitness compensation were selected. Notably, although Hfq is the RNA binding protein, most mutations occurred in Crc. This indicates that Crc is strictly needed for efficient carbon catabolic repression . The compensatory mutations restore in a different degree the alterations in antibiotic susceptibility and virulence of the Δ mutant, supporting that Crc plays a fundamental role linking metabolic robustness, virulence, and antibiotic resistance.