Journal article
Synergy between Nutritional Immunity and Independent Host Defenses Contributes to the Importance of the MntABC Manganese Transporter during Staphylococcus aureus Infection
Infection and immunity, Vol.87(1), 00642
01/01/2019
DOI: 10.1128/IAI.00642-18
PMCID: PMC6300641
PMID: 30348827
Abstract
During infection, the host utilizes a diverse array of processes to combat invaders, including the restriction of availability of essential nutrients such as manganese. Similarly to many other pathogens, Staphylococcus aureus possesses two manganese importers, MntH and MntABC. Several infection models have revealed a critical role for MntABC during staphylococcal infection. However, culture-based studies have suggested parity between the two transporters when cells are resisting manganese starvation imposed by the manganese binding immune effector calprotectin. In this investigation, initial elemental analysis revealed that MntABC is the primary transporter responsible for obtaining manganese in culture in the presence of calprotectin. MntABC was also necessary to maintain wild-type levels of manganese-dependent superoxide dismutase activity in the presence of calprotectin. Building on this framework, we investigated if MntABC enabled S. aureus to resist the synergistic actions of nutritional immunity and other host defenses. This analysis revealed that MntABC critically contributes to staphylococcal growth when S. aureus is subjected to manganese limitations and exposed to oxidative stress. This transporter was also important for growth in manganese-limited environments when S. aureus was forced to consume glucose as an energy source, which occurs when it encounters nitric oxide. MntABC also expanded the pH range conducive for S. aureus growth under conditions of manganese scarcity. Collectively, the data presented in this work provide a robust molecular basis for the crucial role of MntABC in staphylococcal virulence. Further, this work highlights the importance of synergy between host defenses and the necessity of evaluating the contribution of virulence factors to pathogenesis in the presence of multiple stressors.
Details
- Title: Subtitle
- Synergy between Nutritional Immunity and Independent Host Defenses Contributes to the Importance of the MntABC Manganese Transporter during Staphylococcus aureus Infection
- Creators
- Jana N. Radin - University of Illinois Urbana-ChampaignJamie Zhu - University of Illinois Urbana-ChampaignErin B. Brazel - The University of AdelaideChristopher A. McDevitt - Peter Doherty InstituteThomas E. Kehl-Fie - University of Illinois Urbana-Champaign
- Resource Type
- Journal article
- Publication Details
- Infection and immunity, Vol.87(1), 00642
- DOI
- 10.1128/IAI.00642-18
- PMID
- 30348827
- PMCID
- PMC6300641
- NLM abbreviation
- Infect Immun
- ISSN
- 0019-9567
- eISSN
- 1098-5522
- Publisher
- Amer Soc Microbiology
- Number of pages
- 14
- Grant note
- FT170100006 / Australian Research Council 1122582; 1140554 / National Health and Medical Research Council of Australia; National Health & Medical Research Council (NHMRC) of Australia K22 AI104805; RO1 AI18880 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA DP170102102; FT170100006 / Australian Research Council March of Dimes Basil O'Conner award; March of Dimes 1122582; 1140554 / National Health and Medical Research Council; National Health & Medical Research Council (NHMRC) of Australia Vallee Scholars award
- Language
- English
- Date published
- 01/01/2019
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984618641602771
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