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Regulated delayed synthesis of lipopolysaccharide and enterobacterial common antigen of Salmonella Typhimurium enhances immunogenicity and cross-protective efficacy against heterologous Salmonella challenge.

ABSTRACT: Lipopolysaccharide (LPS) O-antigen and enterobacterial common antigen (ECA) are two major polysaccharide structures on the surface of Salmonella enterica serovar Typhimurium. Previous studies have demonstrated that regulated truncation of LPS enhances the cross-reaction against conserved outer membrane proteins (OMPs) from enteric bacteria. We speculate that the regulation of both O-antigen and ECA may enhance the induction of immune responses against conserved OMPs from enteric bacteria. In this work we targeted rfbB and rffG genes which encode dTDP-glucose 4,6-dehydratases and share the same function in regulating O-antigen and ECA synthesis. We constructed a mutant, S496 (?rfbB6 ?rffG7 ?pagL73::TT araC PBADrfbB-3), in which rfbB gene expression was dependent on exogenously supplied arabinose during in vitro growth and achieved the simultaneous tight regulation of both LPS and ECA synthesis, as demonstrated by the LPS profile and Western blotting using antisera against LPS and ECA. When administered orally, S. Typhimurium S496 was completely attenuated for virulence but still retained the capacity to colonize and disseminate in mice. In addition, we found that oral immunization with S496 resulted in increased immune responses against OMPs from enteric bacteria and enhanced survival compared with immunization with S492 possessing ?rfbB6 ?rffG8 mutations when challenged with lethal doses of Salmonella Choleraesuis or Salmonella Enteritidis. These results indicate that S. Typhimurium arabinose-regulated rfbB strain S496 is a good vaccine candidate, conferring cross-protection against lethal challenge with heterologous Salmonella.

SUBMITTER: Huang C

PROVIDER: S-EPMC5206759 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Regulated delayed synthesis of lipopolysaccharide and enterobacterial common antigen of Salmonella Typhimurium enhances immunogenicity and cross-protective efficacy against heterologous Salmonella challenge.

Huang Chun C Liu Qing Q Luo Yali Y Li Pei P Liu Qiong Q Kong Qingke Q

Vaccine 20160801 36

Lipopolysaccharide (LPS) O-antigen and enterobacterial common antigen (ECA) are two major polysaccharide structures on the surface of Salmonella enterica serovar Typhimurium. Previous studies have demonstrated that regulated truncation of LPS enhances the cross-reaction against conserved outer membrane proteins (OMPs) from enteric bacteria. We speculate that the regulation of both O-antigen and ECA may enhance the induction of immune responses against conserved OMPs from enteric bacteria. In thi ...[more]

PMID: 27423383

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Project description:BackgroundBacteria employ complex transcriptional networks involving multiple genes in response to stress, which is not limited to gene and protein networks but now includes small RNAs (sRNAs). These regulatory RNA molecules are increasingly shown to be able to initiate regulatory cascades and modulate the expression of multiple genes that are involved in or required for survival under environmental challenge. Despite mounting evidence for the importance of sRNAs in stress response, their role upon antibiotic exposure remains unknown. In this study, we sought to determine firstly, whether differential expression of sRNAs occurs upon antibiotic exposure and secondly, whether these sRNAs could be attributed to microbial tolerance to antibiotics.ResultsA small scale sRNA cloning strategy of Salmonella enterica serovar Typhimurium SL1344 challenged with half the minimal inhibitory concentration of tigecycline identified four sRNAs (sYJ5, sYJ20, sYJ75 and sYJ118) which were reproducibly upregulated in the presence of either tigecycline or tetracycline. The coding sequences of the four sRNAs were found to be conserved across a number of species. Genome analysis found that sYJ5 and sYJ118 mapped between the 16S and 23S rRNA encoding genes. sYJ20 (also known as SroA) is encoded upstream of the tbpAyabKyabJ operon and is classed as a riboswitch, whilst its role in antibiotic stress-response appears independent of its riboswitch function. sYJ75 is encoded between genes that are involved in enterobactin transport and metabolism. Additionally we find that the genetic deletion of sYJ20 rendered a reduced viability phenotype in the presence of tigecycline, which was recovered when complemented. The upregulation of some of these sRNAs were also observed when S. Typhimurium was challenged by ampicillin (sYJ5, 75 and 118); or when Klebsiella pneumoniae was challenged by tigecycline (sYJ20 and 118).ConclusionsSmall RNAs are overexpressed as a result of antibiotic exposure in S. Typhimurium where the same molecules are upregulated in a related species or after exposure to different antibiotics. sYJ20, a riboswitch, appears to possess a trans-regulatory sRNA role in antibiotic tolerance. These findings imply that the sRNA mediated response is a component of the bacterial response to antibiotic challenge.

Dataset Information

Regulated delayed synthesis of lipopolysaccharide and enterobacterial common antigen of Salmonella Typhimurium enhances immunogenicity and cross-protective efficacy against heterologous Salmonella challenge.

Publications

Regulated delayed synthesis of lipopolysaccharide and enterobacterial common antigen of Salmonella Typhimurium enhances immunogenicity and cross-protective efficacy against heterologous Salmonella challenge.

Similar Datasets

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