Role of transition metal exporters in virulence: the example of Neisseria meningitidis

Abstract

Transition metals such as iron, manganese, and zinc are essential micronutrients for bacteria. However, at high concentration, they can generate non-functional proteins or toxic compounds. Metal metabolism is therefore regulated to prevent shortage or overload, both of which can impair cell survival. In addition, equilibrium among these metals has to be tightly controlled to avoid molecular replacement in the active site of enzymes. Bacteria must actively maintain intracellular metal concentrations to meet physiological needs within the context of the local environment. When intracellular buffering capacity is reached, they rely primarily on membrane-localized exporters to maintain metal homeostasis. Recently, several groups have characterized new export systems and emphasized their importance in the virulence of several pathogens. This article discusses the role of export systems as general virulence determinants. Furthermore, it highlights the contribution of these exporters in pathogens emergence with emphasis on the human nasopharyngeal colonizer Neisseria meningitidis.

Keywords: Neisseria meningitidis; efflux; exporter; metals; virulence factors.

Figure 1

The different families of metal exporters. The different families of metal exporters include the Resistance-Nodulation-Cell division (RND) type transporters, the P-type ATPase family (forming a covalent phosphorylated intermediate), the Cation Diffusion Facilitator (CDF) family, the MntX (Transporter Mediating Manganese Export) family, and the CorA family (Cobalt Resistance protein A). As schematized by a question-mark, the subsequent export from the periplasm to the extracellular space can be mediated via an unknown porin or passively.

Figure 2

The example of Neisseria meningitidis exporters. (A) Candidate for metal exporters encoded in the genomes of three nasopharyngeal pathogens based on the Kyoto Encyclopedia of Genes and Genomes (KEGG database). st stands for strain specific and n.d. for not detected. ^* and ^** represents groups of putative homologous genes determined using blastp similarity. (B) TBlastN of N. meningitidis MC58 proteins against the genome of M. catarrhalis RH4 (Mc). (C) Gene organization of the NMB1732 locus. The genes in gray have common organization between N. meningitidis and N. gonorrhoeae whereas the genes in black are N. meningitidis specific. The white gene, adjacent to NMB1732, corresponds to a remnant of DNA methyltransferase also present in the genome of M. catarrhalis.