Zinc Piracy as a Mechanism of Neisseria meningitidis for Evasion of Nutritional Immunity

PLoS Pathogens

Walter J. Chazin¹  Martine P. Bos²  Carmen Mañas Torres²  Jan Grijpstra²  Jan Tommassen²  Michiel Stork²  Jan T. Poolman³  Nathalie Devos³ 

[1] Department of Biochemistry and Chemistry and Center for Structural Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America;Department of Molecular Microbiology and Institute of Biomembranes, Utrecht University, Utrecht, Netherlands;GlaxoSmithKline Vaccines, Rixensart, Belgium

关键词: Zinc;    Neisseria meningitidis;    Outer membrane proteins;    Nutrients;    Iron;    Membrane receptor signaling;    Immune serum;    Mutant strains;   

DOI  :  10.1371/journal.ppat.1003733

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The outer membrane of Gram-negative bacteria functions as a permeability barrier that protects these bacteria against harmful compounds in the environment. Most nutrients pass the outer membrane by passive diffusion via pore-forming proteins known as porins. However, diffusion can only satisfy the growth requirements if the extracellular concentration of the nutrients is high. In the vertebrate host, the sequestration of essential nutrient metals is an important defense mechanism that limits the growth of invading pathogens, a process known as “nutritional immunity.” The acquisition of scarce nutrients from the environment is mediated by receptors in the outer membrane in an energy-requiring process. Most characterized receptors are involved in the acquisition of iron. In this study, we characterized a hitherto unknown receptor from Neisseria meningitidis, a causative agent of sepsis and meningitis. Expression of this receptor, designated CbpA, is induced when the bacteria are grown under zinc limitation. We demonstrate that CbpA functions as a receptor for calprotectin, a protein that is massively produced by neutrophils and other cells and that has been shown to limit bacterial growth by chelating Zn2+ and Mn2+ ions. Expression of CbpA enables N. meningitidis to survive and propagate in the presence of calprotectin and to use calprotectin as a zinc source. Besides CbpA, also the TonB protein, which couples energy of the proton gradient across the inner membrane to receptor-mediated transport across the outer membrane, is required for the process. CbpA was found to be expressed in all N. meningitidis strains examined, consistent with a vital role for the protein when the bacteria reside in the host. Together, our results demonstrate that N. meningitidis is able to subvert an important defense mechanism of the human host and to utilize calprotectin to promote its growth.

【 授权许可】

CC BY