Host-imposed manganese starvation of invading pathogens: two routes to the same destination
- 471 Downloads
During infection invading pathogens must acquire all essential nutrients, including first row transition metals, from the host. To combat invaders, the host exploits this fact and restricts the availability of these nutrients using a defense mechanism known as nutritional immunity. While iron sequestration is the most well-known aspect of this defense, recent work has revealed that the host restricts the availability of other essential elements, notably manganese (Mn), during infection. Furthermore, these studies have revealed that the host utilizes multiple strategies that extend beyond metal sequestration to prevent bacteria from obtaining these metals. This review will discuss the mechanisms by which bacteria attempt to obtain the essential first row transition metal ion Mn during infection, and the approaches utilized by the host to prevent this occurrence. In addition, this review will discuss the impact of host-imposed Mn starvation on invading bacteria.
KeywordsABC transporter Manganese Zinc Nutritional immunity Calprotectin Infection
We apologize to our colleagues whose work we were unable to cite due to length restrictions. J.R.M. is supported by an Australian Postgraduate Award. This work was supported by the Australian Research Council Grants DP120103957 and DP150104515 to C.A.M., the National Health and Medical Research Council Project Grants 1022240 and 1080784 to C.A.M., and a K22 AI104805 from the National Institutes of Health as well as by Research Grant No. 5-FY15-30 from the March of Dimes Foundation to T.E.K. This work is solely the responsibility of the authors and does not reflect the views of the National Institutes of Health.
Conflict of interest
The authors declare no competing financial interests.
- Bianchi M, Niemiec MJ, Siler U, Urban CF, Reichenbach J (2011) Restoration of anti-Aspergillus defense by neutrophil extracellular traps in human chronic granulomatous disease after gene therapy is calprotectin-dependent. J Allergy Clin Immunol 127(5):1243–1252.e7Google Scholar
- CDC (2013) Antibiotic resistance threats in the United States, 2013. Center for Disease Control and Prevention. http://www.cdc.gov/drugresistance/threat-report-2013/index.html. Accessed 27 March 2014
- Jabado N, Jankowski A, Dougaparsad S, Picard V, Grinstein S, Gros P (2000) Natural resistance to intracellular infections: natural resistance-associated macrophage protein 1 (Nramp1) functions as a pH-dependent manganese transporter at the phagosomal membrane. J Exp Med 192(9):1237–1248CrossRefPubMedCentralPubMedGoogle Scholar
- Korndorfer IP, Brueckner F, Skerra A (2007) The crystal structure of the human (S100A8/S100A9)2 heterotetramer, calprotectin, illustrates how conformational changes of interacting alpha-helices can determine specific association of two EF-hand proteins. J Mol Biol 370(5):887–898CrossRefPubMedGoogle Scholar
- Lippard SJ, Berg JM (1994) Principles of bioinorganic chemistry. University Science Books, Mill ValleyGoogle Scholar
- Lisher JP, Giedroc DP (2013) Manganese acquisition and homeostasis at the host–pathogen interface. Front Cell Infect Microbiol 3:91Google Scholar
- WHO (2003) WHO position paper—Streptococcus pneumoniae. WER 78:110–118Google Scholar
- WHO (2014) Antimicrobial resistance global report on surveillance. World Health Organization, Geneva, SwitzerlandGoogle Scholar