title: Streptococcus suis small RNA rss04 contributes to the induction of meningitis by regulating capsule synthesis and by inducing biofilm formation in a mouse infection model.
abstract: Streptococcus suis (SS) is an important pathogen for pigs, and it is also considered as a zoonotic agent for humans. Meningitis is one of the most common features of the infection caused by SS, but little is known about the mechanisms of SS meningitis. Recent studies have revealed that small RNAs (sRNAs) have emerged as key regulators of the virulence in several bacteria. In the previous study, we reported that SS sRNA rss04 was up-regulated in pig cerebrospinal fluid and contributes to SS virulence in a zebrafish infection model. Here, we show that rss04 facilitates SS invasion of mouse brain and lung in vivo. Label-free quantitation mass spectrometry analysis revealed that rss04 regulates transcriptional regulator CcpA and several virulence factors including LuxS. Transmission electron microscope and Dot-blot analyses indicated that rss04 represses capsular polysaccharide (CPS) production, which in turn facilitates SS adherence and invasion of mouse brain microvascular endothelial cells bEnd.3 in vitro and activates the mRNA expression of TLR2, CCL2, IL-6 and TNF-α in mouse brain in vivo at 12h post-infection. In addition, rss04 positively regulates SS biofilm formation. Survival analysis of infected mice showed that biofilm state in brain contributes to SS virulence by intracranial subarachnoidal route of infection. Together, our data reveal that SS sRNA rss04 contributes to the induction of meningitis by regulating the CPS synthesis and by inducing biofilm formation, thereby increasing the virulence in a mouse infection model. To our knowledge, rss04 represents the first bacterial sRNA that plays definitive roles in bacterial meningitis.
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China.
authors.forename: Genhui
authors.initials: G
authors.lastname: Xiao
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China.
authors.forename: Huanyu
authors.initials: H
authors.lastname: Tang
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China.
authors.forename: Shouming
authors.initials: S
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Ren
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Dai
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China.
authors.forename: Liying
authors.initials: L
authors.lastname: Lai
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China.
authors.forename: Chengping
authors.initials: C
authors.lastname: Lu
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China.
authors.forename: Huochun
authors.initials: H
authors.lastname: Yao
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Fan
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China; OIE Reference Lab for Swine Streptococcosis, Nanjing 210095, China. Electronic address: wuzongfu@njau.edu.cn.
authors.forename: Zongfu
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D016667:Bacterial Capsules / Q000235:genetics / Q000378:metabolism; D018441:Biofilms; D001921:Brain / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D008168:Lung / Q000382:microbiology; D008581:Meningitis / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012329:RNA, Bacterial / Q000378:metabolism*; D013290:Streptococcal Infections / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D017011:Streptococcus suis / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D012329:RNA, Bacterial; D037521:Virulence Factors
keywords: Biofilm; Capsular polysaccharide; Meningitis; Small RNA; Streptococcus suis