*Article* **Differential Expression of** *Yersinia pseudotuberculosis* **General Porin Genes during Short- and Long-Term Antibiotic Stresses**

**Evgeniya Bystritskaya 1, Nadezhda Chernysheva 1, Anna Stenkova 2, Konstantin Guzev 1, Alexander Rakin <sup>3</sup> and Marina Isaeva 1,2,\***


**Abstract:** Here, we investigated general porin regulation in *Yersinia pseudotuberculosis* 488, the causative agent of Far Eastern scarlet-like fever, in response to sublethal concentrations of antibiotics. We chose four antibiotics of different classes and measured gene expression using qRT-PCR and GFP reporter systems. Our data showed temporal regulation of the general porin genes *ompF* and *ompC* caused by antibiotic stress. The porin transcription initially decreased, providing early defensive response of the bacterium, while it returned to that of the untreated cells on prolonged antibiotic exposure. Unlike the major porin genes, the transcription of the alternative porin genes *ompX* and *lamB* was increased. Moreover, a short-term *ompR*- and *marA*-mediated porin regulation was observed. The main finding was a phenotypic heterogeneity of *Y. pseudotuberculosis* population manifested in variable porin gene expression under carbenicillin exposure. This may offer adaptive fitness advantages for a particular bacterial subpopulation.

**Keywords:** porin gene expression; *Yersinia pseudotuberculosis*; antibiotic stress; phenotypic heterogeneity
