title: The expression levels of outer membrane proteins STM1530 and OmpD, which are influenced by the CpxAR and BaeSR two-component systems, play important roles in the ceftriaxone resistance of Salmonella enterica serovar Typhimurium.
abstract: Significant increases in STM3031, STM1530, and AcrD protein levels and significant decreases in OmpC and OmpD protein levels are present when the ceftriaxone-resistant Salmonella enterica serovar Typhimurium R200 strain is compared with the ceftriaxone-susceptible strain 01-4. AcrD is known to be involved in drug export, and STM3031 seems to play a key role in ceftriaxone resistance. Here, we examine the roles of STM1530, OmpC, and OmpD in ceftriaxone resistance. An ompD gene deletion mutant showed 4-fold higher ceftriaxone resistance than 01-4. An ompC gene deletion mutant showed 4-fold higher cephalothin and erythromycin resistance than 01-4, but there was no effect on ceftriaxone resistance. However, a stm1530 deletion mutant did show >64-fold lower ceftriaxone resistance than R200. Moreover, the STM3031 protein was significantly decreased in R200(Δstm1530) compared to R200. STM3031 expression has been shown to be influenced by the two-component system regulator gene baeR. CpxR seems to modulate BaeR. A cpxA-cpxR gene deletion mutant showed >2,048-fold lower ceftriaxone resistance than R200. The outer membrane protein profile of R200(ΔcpxAR) showed significant decreases in STM3031 and STM1530 compared to R200, while OmpD had returned to the level found in 01-4. Furthermore, the stm3031, stm1530, and ompD mRNA levels were correlated with their protein expression levels in these strains, while decreases in the mRNA levels of the efflux pump acrB, acrD, and acrF genes were found in R200(ΔcpxAR). Findings similar to those for R200(ΔcpxAR) were found for R200(ΔbaeSR). These results, together with those for STM3031 and the fact that STM1530 is an outer membrane protein, suggest that STM1530 and OmpD are influenced by the CpxAR and BaeSR two-component systems and that this contributes to S. enterica serovar Typhimurium ceftriaxone resistance.
authors.affiliation: Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan. huws@ym.edu.tw
authors.forename: Wensi S
authors.initials: WS
authors.lastname: Hu
authors.forename: Hung-Wen
authors.initials: HW
authors.lastname: Chen
authors.forename: Rui-Yang
authors.initials: RY
authors.lastname: Zhang
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Huang
authors.forename: Chi-Fan
authors.initials: CF
authors.lastname: Shen
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D001426:Bacterial Proteins / Q000378:metabolism; D002443:Ceftriaxone / Q000494:pharmacology*; D018550:Cephalosporin Resistance; D015964:Gene Expression Regulation, Bacterial; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D018272:Porins / Q000096:biosynthesis / Q000235:genetics; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002443:Ceftriaxone; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D018272:Porins; D011494:Protein Kinases; D012333:RNA, Messenger; D015534:Trans-Activators; C525553:BaeR protein, Salmonella typhimurium; C470933:OmpD protein, Salmonella typhimurium; C085504:CpxR protein, Bacteria; C525552:BaeS protein, Salmonella typhimurium; C092472:CpxA protein, bacteria