TamAB is regulated by PhoPQ and functions in outer membrane homeostasis during Salmonella pathogenesis

Rouhallah Ramezanifard, Yekaterina A. Golubeva, Alexander D. Palmer, James M. Slauch

Research output: Contribution to journalArticlepeer-review

Abstract

Salmonella survive and replicate in macrophages, which normally kill bacteria by exposing them to a variety of harsh conditions and antimicrobial effectors,many of which target the bacterial cell envelope. The PhoPQ two-component system responds to the phagosome environment and induces factors that protect the outer membrane, allowing adaptation and growth in the macrophage. We show that PhoPQ induces the transcription of the tamAB operon both in vitro and in macrophages. The TamA protein is structurally similar to BamA, an essential protein in the Bam complex that assembles β-barrel proteins in the outer membrane, while TamB is an AsmA-family protein implicated in lipid transport between the inner and outer membranes. We show that the Bam machinery is stressed in vitro under low Mg2+, low pH conditions that mimic the phagosome. Not surprisingly, mutations affectingBam function confer significantvirulence defects. Although loss of TamAB alone confers no virulence defect, a tamAB deletion confers a synthetic phenotype in bam mutant backgrounds in animals and macrophages, and in vitro upon treatment with vancomycin or sodium dodecyl sulfate. Mutations affectingYhdP, which functions in partial redundancy with TamB, also confer synthetic phenotypes with bam mutations in the animal, but this interaction is not evident in vitro. Thus, in the harsh phagocytic environment of the macrophage, the outer membrane Bam machinery is compromised, and the TamAB system, and perhaps other PhoPQ-regulated factors, is induced to compensate. It is most likely that TamAB and other systems assist the Bam complex indirectly by affectingouter membrane properties.

Original languageEnglish (US)
JournalJournal of bacteriology
Volume205
Issue number10
DOIs
StatePublished - Oct 2023

Keywords

  • BAM complex
  • Salmonella
  • TamAB
  • outer membrane biogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

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