[ODP-089] Staphylococcus aureus silence accessory gene regulator to be persistent and competent in hospital
Methicillin-resistant Staphylococcus aureus (MRSA) outbreak is a serious health issue worldwide. To understand the mechanism how pathogenic bacteria thrive in a hospital, we analyzed MRSA clinical isolates in neonatal intensive care unit (NICU) outbreak and found 18 out of 21 isolates were identified as the same lineage. The outbreak lineage evolved to silence the key regulator of MRSA virulence, the accessory gene regulator (Agr), under hypoxia, while two clones acquired loss-of-function mutations in agr locus. The clones not expressing Agr showed higher probabilities of becoming persister under antibiotic stress in vitro. On the other hand, one outbreak clone acquired the gentamicin resistance gene within a year after silencing Agr. S. aureus strains not expressing Agr took up exogenous gene materials more efficiently than Agr-expressing clones in vitro. The whole-genome sequencing revealed that large genomic clusters were acquired only in the clones with silenced Agr. Therefore, our findings propose the bacterial evolution to fit into the environment occurs in multistep ways: S. aureus evolved first by gaining the fluctuating Agr that warranted bacteria to change behavior depending on the aerobic condition. By silencing Agr function under hypoxia, the bacteria became persistent and competent to gain exogenous genes encoding suitable function to thrive in hospital.