(823.2) Role of EnvZ/OmpR Two-component System in Antibiotic Resistance in Salmonella enterica Serovar Enteritidis

Poster Board Number: A454

Duhyun Ko (Seoul National University), Garam Choi (Seoul National University), Dayoung Sung (Seoul National University), Sang Ho Choi (Seoul National University)

Outer membrane porins (OMPs) form water-filled open channels and allow the entry of small hydrophilic antibiotics. Thus, compositional modulation of OMPs is frequently observed in multidrug-resistant bacteria, including a human pathogen Salmonella enterica. However, the mechanism by which S. enterica modulates OMP composition to enhance antibiotic resistance has not been well elucidated. In this study, we found that the S. enterica serovar Enteritidis strain with an active state of EnvZ/OmpR is highly resistant to various antibiotics, especially β-lactams. Transcriptome analysis discovered that the active state of EnvZ/OmpR induces differential expression of multiple OMP genes, including SEN1522, SEN2875, ompD, and ompW. Biochemical analyses identified that OmpR activates SEN1522 and SEN2875 but represses ompD and ompW by directly binding to their upstream regions. Interestingly, the cellular level of OmpR determines the expression of the four OMP genes, and particularly, the phosphorylation of OmpR is not required for the repression of ompD and ompW. Phenotypic analysis revealed that a decreased expression of ompD is responsible for the EnvZ/OmpR-mediated resistance to β-lactams in S. Enteritidis. Notably, EnvZ/OmpR represses the expression of ompD upon exposure to β-lactams and presumably provides S. Enteritidis with benefits for survival. Altogether, this study suggests that EnvZ/OmpR remodels OMP composition in response to β-lactams and thereby enhances resistance in S. Enteritidis to the antibiotics.

Support or Funding Information

This work was supported by the National Research Foundation of Korea, funded by the Ministry of Science, ICT, and Future Planning (2017R1E1A1A01074639 and 2021K1A3A1A20001134) to SHC.