Genes required for phosphosphingolipid formation in Caulobacter crescentus contribute to bacterial virulence

PLoS Pathog. 2024 Aug 2;20(8):e1012401. doi: 10.1371/journal.ppat.1012401. eCollection 2024 Aug.

Abstract

Sphingolipids are ubiquitous in membranes of eukaryotes and are associated with important cellular functions. Although sphingolipids occur scarcely in bacteria, for some of them they are essential and, in other bacteria, they contribute to fitness and stability of the outer membrane, such as in the well-studied α-proteobacterium Caulobacter crescentus. We previously defined five structural genes for ceramide synthesis in C. crescentus, among them the gene for serine palmitoyltransferase, the enzyme that catalyzes the committed step of sphingolipid biosynthesis. Other mutants affected in genes of this same genomic region show cofitness with a mutant deficient in serine palmitoyltransferase. Here we show that at least two phosphosphingolipids are produced in C. crescentus and that at least another six gene products are needed for the decoration of ceramide upon phosphosphingolipid formation. All eleven genes participating in phosphosphingolipid formation are also required in C. crescentus for membrane stability and for displaying sensitivity towards the antibiotic polymyxin B. The genes for the formation of complex phosphosphingolipids are also required for C. crescentus virulence on Galleria mellonella insect larvae.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Caulobacter crescentus* / genetics
  • Caulobacter crescentus* / metabolism
  • Moths / microbiology
  • Serine C-Palmitoyltransferase / genetics
  • Serine C-Palmitoyltransferase / metabolism
  • Sphingolipids* / metabolism
  • Virulence

Substances

  • Sphingolipids
  • Bacterial Proteins
  • Serine C-Palmitoyltransferase

Grants and funding

This work was supported by grants from the Consejo Nacional de Ciencia y Tecnología de México (178359 & 253549, to OG) in Investigación Científica Básica as well as (118, to OG) in Investigación en Fronteras de la Ciencia). Additional funding for this study was obtained by the Programa de Apoyo a Projectos de Investigación e Innovación Tecnologica of the Dirección General de Asuntos del Personal Académico of the Universidad Nacional Autómoma de México (IN201120 & IN202223, to OG). The mass spectrometric analyses were carried out in the York Centre of Excellence in Mass Spectrometry, which was created thanks to a major capital investment through Science City York, supported by Yorkshire Forward with funds from the Northern Way Initiative, and subsequent support from the Engineering and Physical Sciences Research Council (EP/K039660/1 & EP/M028127/1, to JTO). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.