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Cronobacter sakazakii infection implicates multifaceted neuro-immune regulatory pathways of Caenorhabditis elegans

ABSTRACT: Background: The nervous and immune systems are inextricably interlinked. Protein therapy strategies are the most advanced methods for treating neurodegenerative diseases. Albeit the technologies and facilities have developed in modern medicine, still there are no proper treatments to pathogen specific neurodegenerative diseases. It is crucial to understand how host proteins regulate neuron-immune communication during pathogenesis. The emerging opportunistic foodborne pathogen Cronobacter sakazakii causes life-threatening infections such as meningitis, necrotizing enterocolitis, sepsis, and meningo-encephalitis most predominantly in neonates, infants, and immunocompromised patients, with a relatively high mortality rate. In our study, C. elegans infected with the above pathogen have been analyzed primarily at the translational level, especially profiling the differentially regulated proteins involved in neuro-immune signaling pathways. Results: The protein profiling of both control and infected worms using LC-MS/MS analysis revealed a total of 174 proteins in control, 206 in C. sakazakii infected at 24 h, and 172 proteins in control and 226 in C. sakazakii infected at 48 h samples. We observed 69 differentially regulated proteins from both control and infected samples. Protein-protein interaction networks constructed using STRING tool suggested that molecular players were involved in mTOR, axon regeneration, calcium signaling, and longevity regulating pathways. Conclusions: This study identified distinct protein regulations in C. elegans associated to neuro-immune communication in response to C. sakazakii infection.

INSTRUMENT(S): 6545 Q-TOF LC/MS

ORGANISM(S): Caenorhabditis Elegans

TISSUE(S): Whole Body

SUBMITTER: BALAMURUGAN KRISHNASWAMY

LAB HEAD: Krishnaswamy Balamurugan

PROVIDER: PXD041315 | Pride | 2023-10-13

REPOSITORIES: Pride

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Cronobacter sakazakii infection implicates multifaceted neuro-immune regulatory pathways of Caenorhabditis elegans.

VenkataKrishna Lappasi Mohanram LM Balasubramaniam Boopathi B Sushmitha T J TJ Ravichandiran V V Balamurugan Krishnaswamy K

Molecular omics 20240115 1

The neural pathways of Caenorhabditis elegans play a crucial role in regulating host immunity and inflammation during pathogenic infections. To understand the major neuro-immune signaling pathways, this study aimed to identify the key regulatory proteins in the host C. elegans during C. sakazakii infection. We used high-throughput label-free quantitative proteomics and identified 69 differentially expressed proteins. KEGG analysis revealed that C. sakazakii elicited h ...[more]

PMID: 37818754

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Project description:C. elegans has served as a laboratory model organism due to its ease of manipulation and the availability of both forward and reverse genetics. In recent years, efforts to study host-pathogen interactions in C. elegans have increased. For example, analysis of infections by bacteria such as Pseudomonas, Salmonella or Serratia has revealed the existence of innate immune pathways in C. elegans that are also conserved in vertebrates. To date, there has been no natural virus infection reported in C. elegans or C. briggsae. Here we describe evidence of natural virus infection in wild isolates of both C. elegans and C. briggsae. Two highly divergent but related RNA viruses in the family Nodaviridae, tentatively named Orsay nodavirus and Santeuil nodavirus, were detected and their genomes partially sequenced. Infected worm lysates passed through 0.2 um filters could be used to infect uninfected worms, which could be further passaged for many generations. Furthermore, the viruses were subject to processing by the RNAi machinery as evidenced by the detection of virally derived small RNAs. Infection of mutant worms defective in small RNA pathways yielded more robust levels of viral RNA as compared to infection of isogenic N2 reference worms. These data demonstrate that nodaviruses are natural parasites of nematodes in the wild. Further study of the interactions between these viruses and nematodes is likely to provide insight into the natural ecology of nematodes and may reveal novel innate immune mechanisms that respond to viral infection. Two small RNA libraries (18-30 nt) from nodavirus-infected and cured C. elegans wild isolate JU1580 were sequenced on the Illumina Genome Analyzer II platform. Samples were treated with tobacco acid pyrophosphatase to allow cloning of small RNA molecules with 5'-triphosphates. Each sample was labelled with a unique four base pair barcode and libraries were multiplexed together with a third library (not included in this submission). The multiplexed libraries were sequenced in triplicate.

Dataset Information

Cronobacter sakazakii infection implicates multifaceted neuro-immune regulatory pathways of Caenorhabditis elegans

Publications

<i>Cronobacter sakazakii</i> infection implicates multifaceted neuro-immune regulatory pathways of <i>Caenorhabditis elegans</i>.

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