The Staphylococcus aureus ABC-Type Manganese Transporter MntABC Is Critical for Reinitiation of Bacterial Replication Following Exposure to Phagocytic Oxidative Burst.

Abstract

Manganese plays a central role in cellular detoxification of reactive oxygen species (ROS). Therefore, manganese acquisition is considered to be important for bacterial pathogenesis by counteracting the oxidative burst of phagocytic cells during host infection. However, detailed analysis of the interplay between bacterial manganese acquisition and phagocytic cells and its impact on bacterial pathogenesis has remained elusive for Staphylococcus aureus, a major human pathogen. Here, we show that a mntC mutant, which lacks the functional manganese transporter MntABC, was more sensitive to killing by human neutrophils but not murine macrophages, unless the mntC mutant was pre-exposed to oxidative stress. Notably, the mntC mutant formed strikingly small colonies when recovered from both type of phagocytic cells. We show that this phenotype is a direct consequence of the inability of the mntC mutant to reinitiate growth after exposure to phagocytic oxidative burst. Transcript and quantitative proteomics analyses revealed that the manganese-dependent ribonucleotide reductase complex NrdEF, which is essential for DNA synthesis and repair, was highly induced in the mntC mutant under oxidative stress conditions including after phagocytosis. Since NrdEF proteins are essential for S. aureus viability we hypothesize that cells lacking MntABC might attempt to compensate for the impaired function of NrdEF by increasing their expression. Our data suggest that besides ROS detoxification, functional manganese acquisition is likely crucial for S. aureus pathogenesis by repairing oxidative damages, thereby ensuring efficient bacterial growth after phagocytic oxidative burst, which is an attribute critical for disseminating and establishing infection in the host.

• Authors: Alison Coady, Min Xu, Qui Phung, Tommy K Cheung, Corey Bakalarski, Mary Kate Alexander, Sophie M Lehar, Janice Kim, Summer Park, Man-Wah Tan, Mireille Nishiyama
• Journal: PloS one (PLoS One) Vol. 10 Issue 9 Pg. e0138350 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26379037 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Proteins
• Membrane Transport Proteins
• Reactive Oxygen Species
• Manganese

Topics

• Animals
• Bacterial Proteins (genetics)
• DNA Replication (genetics)
• Gene Expression Regulation, Bacterial (genetics)
• Humans
• Macrophages (microbiology)
• Manganese (metabolism)
• Membrane Transport Proteins (genetics)
• Mice
• Neutrophils (microbiology)
• Oxidative Stress (genetics)
• Phagocytosis (genetics)
• Proteomics (methods)
• Reactive Oxygen Species (metabolism)
• Respiratory Burst (genetics)
• Staphylococcal Infections (microbiology)
• Staphylococcus aureus (genetics, metabolism)