RssAB-FlhDC-ShlBA as a major pathogenesis pathway in Serratia marcescens

Chuan Sheng Lin, Jim Tong Horng, Chun Hung Yang, Yu Huan Tsai, Lin Hui Su, Chia Fong Wei, Chang Chieh Chen, Shang Chen Hsieh, Chia Chen Lu, Hsin Chih Lai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Serratia marcescens has long been recognized as an important opportunistic pathogen, but the underlying pathogenesis mechanism is not completely clear. Here, we report a key pathogenesis pathway in S. marcescens comprising the RssAB two-component system and its downstream elements, FlhDC and the dominant virulence factor hemolysin ShlBA. Expression of shlBA is under the positive control of FlhDC, which is repressed by RssAB signaling. At 37°C, functional RssAB inhibits swarming, represses hemolysin production, and promotes S. marcescens biofilm formation. In comparison, when rssBA is deleted, S. marcescens displays aberrant multicellularity favoring motile swarming with unbridled hemolysin production. Cellular and animal infection models further demonstrate that loss of rssBA transforms this opportunistic pathogen into hypervirulent phenotypes, leading to extensive inflammatory responses coupled with destructive and systemic infection. Hemolysin production is essential in this context. Collectively, a major virulence regulatory pathway is identified in S. marcescens.

Original languageEnglish
Pages (from-to)4870-4881
Number of pages12
JournalInfection and Immunity
Volume78
Issue number11
DOIs
StatePublished - Nov 2010

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