外膜蛋白 STM1530 和 OmpD 的表达水平受 CpxAR 和 BaeSR 双组分系统的影响，在鼠伤寒沙门氏菌头孢曲松耐药性中发挥重要作用。
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.
机构信息
Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan.
出版信息
Antimicrob Agents Chemother. 2011 Aug;55(8):3829-37. doi: 10.1128/AAC.00216-11. Epub 2011 Jun 6.
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.
当比较头孢曲松耐药的沙门氏菌血清型 Typhimurium R200 菌株与头孢曲松敏感菌株 01-4 时，发现 STM3031、STM1530 和 AcrD 蛋白水平显著增加，而 OmpC 和 OmpD 蛋白水平显著降低。AcrD 已知参与药物外排，而 STM3031 似乎在头孢曲松耐药中发挥关键作用。在这里，我们研究了 STM1530、OmpC 和 OmpD 在头孢曲松耐药中的作用。ompD 基因缺失突变体比 01-4 对头孢曲松的耐药性高出 4 倍。ompC 基因缺失突变体对头孢噻肟和红霉素的耐药性比 01-4 高出 4 倍，但对头孢曲松的耐药性没有影响。然而，stm1530 缺失突变体对头孢曲松的耐药性比 R200 低 >64 倍。此外，与 R200 相比，R200(Δstm1530)中的 STM3031 蛋白显著减少。STM3031 的表达已被证明受双组分系统调节基因 baeR 的影响。CpxR 似乎调节 BaeR。CpxA-cpxR 基因缺失突变体对头孢曲松的耐药性比 R200 低 >2,048 倍。R200(ΔcpxAR)的外膜蛋白图谱与 R200 相比，STM3031 和 STM1530 显著减少，而 OmpD 则恢复到 01-4 中的水平。此外，这些菌株中 STM3031、STM1530 和 ompDmRNA 水平与蛋白表达水平相关，而 R200(ΔcpxAR)中发现外排泵 acrB、acrD 和 acrF 基因的 mRNA 水平降低。R200(ΔbaeSR)的发现与 R200(ΔcpxAR)的发现相似。这些结果以及 STM3031 的结果，以及 STM1530 是一种外膜蛋白的事实表明，STM1530 和 OmpD 受 CpxAR 和 BaeSR 双组分系统的影响，这有助于沙门氏菌血清型 Typhimurium 对头孢曲松的耐药性。
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