A gene encoding a non-functional tyrosine phosphatase is required for the delayed maturation of the bacteria-containing vacuoles in macrophages Free

Abstract

infects patients with cystic fibrosis. We have previously shown that can survive in macrophages within membrane vacuoles [-containing vacuoles (BcCVs)] that preclude fusion with the lysosome. The bacterial factors involved in intracellular survival are not fully elucidated. We report here that deletion of BCAM0628, encoding a predicted low molecular weight protein tyrosine phosphatase (LMW-PTP) that is restricted to strains of the transmissible ET-12 clone, accelerates the maturation of the BcCVs. Compared to the parental strain and deletion mutants in other LMW-PTPs that are widely conserved in species, a greater proportion of BcCVs containing the Δ mutant were targeted to the lysosome. Accelerated BcCV maturation was not due to reduced intracellular viability since Δ survived and replicated in macrophages similarly to the parental strain. Therefore, BCAM0628 was referred to as (elayed hagosome aturation). We provide evidence that the Dpm protein is secreted during growth and upon macrophage infection. Dpm secretion requires an N-terminal signal peptide. Heterologous expression of Dpm in confers to this bacterium a similar phagosomal maturation delay to that found with . We demonstrate that Dpm is an inactive phosphatase, suggesting that its contribution to phagosomal maturation arrest must be unrelated to tyrosine phosphatase activity.

Funding
This study was supported by the:
  • Cystic Fibrosis Canada
  • UK Cystic Fibrosis Trust
  • Government of Canada
  • Consejo Nacional de Ciencia y Tecnología of Mexico
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2014-07-01
2024-03-28
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