Department of Biosystems Sciences and Engineering, Indian Institute of Science, Bangalore, Karnataka, INDIA.
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, Karnataka, INDIA.
J Med Microbiol. 2020 Jun;69(6):906-919. doi: 10.1099/jmm.0.001199. Epub 2020 May 21.
Indwelling medical devices such as endotracheal tubes (ETTs), urinary catheters, vascular access devices, tracheostomies and feeding tubes are often associated with hospital-acquired infections. Bacterial biofilm formed on the ETTs in intubated patients is a significant risk factor associated with ventilator-associated pneumonia. is one of the four frequently encountered bacteria responsible for causing pneumonia, and the biofilm formation on ETTs. However, understanding of biofilm formation on ETT and interventions to prevent biofilm remains lagging. The ability to sense and adapt to external cues contributes to their success. Thus, the biofilm formation is likely to be influenced by the two-component systems (TCSs) that are composed of a membrane-associated sensor kinase and an intracellular response regulator. This study aims to establish an method to analyse the biofilm formation on ETTs, and identify the TCSs that contribute to this process. In total, 112 PA14 TCS mutants were tested for their ability to form biofilm on ETTs, their effect on quorum sensing (QS) and motility. Out of 112 TCS mutants studied, 56 had altered biofilm biomass on ETTs. Although the biofilm formation on ETTs is QS-dependent, none of the 56 loci controlled quorum signal. Of these, 18 novel TCSs specific to ETT biofilm were identified, namely, AauS, AgtS, ColR, CopS, CprR, NasT, KdpD, ParS, PmrB, PprA, PvrS, RcsC, PA14_11120, PA14_32580, PA14_45880, PA14_49420, PA14_52240, PA14_70790. The set of 56 included the GacS network, TCS proteins involved in fimbriae synthesis, TCS proteins involved in antimicrobial peptide resistance, and surface-sensing. Additionally, several of the TCS-encoding genes involved in biofilm formation on ETTs were found to be linked to flagellum-dependent swimming motility. Our study established an method for studying biofilm formation on the ETT surfaces. We also identified novel ETT-specific TCSs that could serve as targets to prevent biofilm formation on indwelling devices frequently used in clinical settings.
留置医疗设备，如气管内管（ETT）、导尿管、血管通路装置、气管造口术和喂养管，常与医院获得性感染有关。在插管患者中，ETT 上形成的细菌生物膜是与呼吸机相关性肺炎相关的重要危险因素。铜绿假单胞菌是导致肺炎的四种常见细菌之一，也是 ETT 生物膜形成的原因之一。然而，对于 ETT 生物膜形成的理解以及预防生物膜的干预措施仍然滞后。它们成功的原因之一是能够感知和适应外部线索。因此，生物膜的形成可能受到由膜相关传感器激酶和细胞内反应调节剂组成的双组分系统（TCS）的影响。本研究旨在建立一种分析 ETT 上铜绿假单胞菌生物膜形成的方法，并确定有助于该过程的 TCS。总共测试了 112 个 PA14 TCS 突变体在 ETT 上形成生物膜的能力、对群体感应（QS）和运动性的影响。在研究的 112 个 TCS 突变体中，有 56 个突变体改变了 ETT 上的生物膜生物量。尽管 ETT 上的生物膜形成依赖于 QS，但没有一个 56 个位点控制群体信号。其中，确定了 18 种新型特定于 ETT 生物膜的 TCS，即 AauS、AgtS、ColR、CopS、CprR、NasT、KdpD、ParS、PmrB、PprA、PvrS、RcsC、PA14_11120、PA14_32580、PA14_45880、PA14_49420、PA14_52240、PA14_70790。这一组包括 GacS 网络、参与菌毛合成的 TCS 蛋白、参与抗抗菌肽抗性的 TCS 蛋白以及表面感应。此外，还发现一些参与 ETT 上生物膜形成的 TCS 编码基因与依赖鞭毛的游动运动有关。我们的研究建立了一种研究 ETT 表面生物膜形成的方法。我们还确定了新型的 ETT 特异性 TCS，可作为预防临床常用留置装置生物膜形成的靶点。
