Beware of proteins bearing gifts: protein antibiotics that use iron as a Trojan horse

Abstract

Multicellular organisms limit the availability of free iron to prevent the utilization of this essential nutrient by microbial pathogens. As such, bacterial pathogens possess a variety of mechanisms for obtaining iron from their hosts, including a number of examples of vertebrate pathogens that obtain iron directly from host proteins. Recently, two novel members of the colicin M bacteriocin family were discovered in Pectobacterium that suggest that this phytopathogen possesses such a system. These bacteriocins (pectocin M1 and M2) consist of a cytotoxic domain homologous to that of colicin M fused to a horizontally acquired plant-like ferredoxin. This ferredoxin domain substitutes the portion of colicin M required for receptor binding and translocation, presumably fulfilling this role by parasitizing an existing ferredoxin-based iron acquisition pathway. The ability of susceptible strains of Pectobacterium to utilize plant ferredoxin as an iron source was also demonstrated, providing additional evidence for the existence of such a system. If this hypothesis is correct, it represents the first example of iron piracy directly from a host protein by a phytopathogen and serves as a testament of the flexibility of evolution in creating new bacteriocin specificities.

Thiostrepton hijacks pyoverdine receptors to inhibit growth ofPseudomonas aeruginosa

“…Specialized receptors then transport siderophore-iron complexes back into the cell. Some antimicrobials, including sideromycins, pyocins, and bacteriocins, use siderophore receptors to access intracellular targets (31–34), and we hypothesized that TS may use this strategy. We compared P. aeruginosa PAO1 grown in 10:90 with increasing concentrations of TS alone ( Fig 3A ) or with 0.1μM EDDHA, a membrane-impermeable iron chelator (35) ( Fig 3B ).…”

Can Plant Microbiome Studies Lead to Effective Biocontrol of Plant Diseases?

“…The narrow range of specificity of the second antibiotic, agrocin 434 (Rhizobium rhizogenes), is also consistent with a Trojan horse function, although its full chemical structure and mode of action are unknown. Several other narrow specificity Trojan horse antibiotics that involve a toxic component and a second component for high-efficiency delivery into target cells have now been identified in other bacterial species and have been investigated to develop synthetic, narrow-spectrum, high-activity antibiotics for human medicine (Grinter et al 2013;Rebuffat 2012).…”

Structure of the atypical bacteriocin pectocin M2 implies a novel mechanism of protein uptake

“…We recently described the novel M-class bacteriocins pectocin M1 and M2, which are produced by and active against strains of the soft-rot phytopathogens Pectobacterium atrosepticum (Pba) and Pectobacterium carotovorum (Pbc) (Grinter et al ., 2012a; 2013 , ). The domain structure of these proteins suggested that they challenge the dogma that an IUTD is the universal mechanism by which colicin-like bacteriocins achieve translocation.…”