Oligoribonuclease is required for the type III secretion system and pathogenesis of Pseudomonas aeruginosa.
Oligoribonuclease (Orn) is a 3' to 5' exonuclease that degrades nanoRNAs, which can serve as primers for transcription initiation at a significant fraction of promoters. One of Orn's substrates, pGpG inhibits the enzymatic activity of EAL-domain containing phosphodiesterases (PDEs), thereby increasing intracellular cyclic-di-GMP (c-di-GMP) level. Here, we found that an orn mutant of Pseudomonas aeruginosa displayed reduced cytotoxicity, which was mainly due to deficient type III secretion system (T3SS). Given the importance of T3SS in pathogenicity, we examined the bacterial virulence in a mouse acute pneumonia model and found that the Δorn mutant was highly attenuated compared to the wild type PA14 strain. Overexpression of an EAL domain-containing PDE reduced the c-di-GMP level as well as biofilm formation in the Δorn mutant. However, no effect was observed on the expression of T3SS genes, suggesting that increased c-di-GMP level is not the solely cause of defective T3SS in the Δorn mutant. Overall, our results demonstrated an essential role of Orn in the expression of T3SS as well as pathogenesis of P. aeruginosa.
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Gukui
G
Chen
College of Life Sciences, Nankai University, Tianjin 300071, China.
Qiang
Q
Zhao
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Feng
F
Zhu
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Ronghao
R
Chen
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Yongxin
Y
Jin
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Chang
C
Liu
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Xiaolei
X
Pan
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China; Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Shouguang
S
Jin
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Weihui
W
Wu
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address: zhihuicheng@nankai.edu.cn.
Zhihui
Z
Cheng
D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism; D018441:Biofilms / Q000254:growth & development; D002470:Cell Survival / Q000187:drug effects; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018410:Pneumonia, Bacterial / Q000382:microbiology / Q000473:pathology; D021381:Protein Transport; D011552:Pseudomonas Infections / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D000069296:Type III Secretion Systems; D037521:Virulence Factors / Q000378:metabolism
D001427:Bacterial Toxins; D000069296:Type III Secretion Systems; D037521:Virulence Factors; C062025:bis(3',5')-cyclic diguanylic acid; D005095:Exoribonucleases; C094587:oligoribonuclease; D006152:Cyclic GMP
Oligoribonuclease; Pathogenesis; Pseudomonas aeruginosa; Type III secretion system