RssAB-FlhDC-ShlBA as a major pathogenesis pathway in Serratia marcescens.
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.
Lin
Chuan-Sheng
CS
Department of Medical Biotechnology and Laboratory Science, Chang-Gung University, Kweishan, Taoyuan, Taiwan, Republic of China.
Horng
Jim-Tong
JT
Yang
Chun-Hung
CH
Tsai
Yu-Huan
YH
Su
Lin-Hui
LH
Wei
Chia-Fong
CF
Chen
Chang-Chieh
CC
Hsieh
Shang-Chen
SC
Lu
Chia-Chen
CC
Lai
Hsin-Chih
HC
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology / Q000382:microbiology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism*; D006461:Hemolysis; D006801:Humans; D008297:Male; D018410:Pneumonia, Bacterial / Q000382:microbiology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016868:Serratia Infections / Q000382:microbiology / Q000473:pathology; D012706:Serratia marcescens / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D015398:Signal Transduction; D014774:Virulence
D001426:Bacterial Proteins; D006460:Hemolysin Proteins; C089911:ShlA protein, Serratia marcescens; C107896:ShlB protein, Serratia marcescens