Disease relevance of tonB

• Requirement of the Pseudomonas aeruginosa tonB gene for high-affinity iron acquisition and infection [1].
• TonB-dependent iron transporters present in the outer membranes of Gram-negative bacteria transport ferric-siderophore complexes into the periplasm [2].
• Nuclear magnetic resonance solution structure of the periplasmic signalling domain of the TonB-dependent outer membrane transporter FecA from Escherichia coli [3].
• Haem utilization in Vibrio cholerae involves multiple TonB-dependent haem receptors [4].
• CjrA protein was homologous to iron-regulated Pseudomonas aeruginosa protein PhuW, whose function is unknown; CjrB was homologous to the TonB protein from Pseudomonas putida; and CjrC was homologous to a putative outer membrane siderophore receptor from Campylobacter jejuni [5].

High impact information on tonB

• This is a novel protein fold which appears to be preserved in all the periplasmic signalling domains of bacterial TonB-dependent outer membrane receptors that are involved in ECF signalling, because the hydrophobic residues that make up the core of the protein domain are highly conserved [3].
• A low-iron milieu led to increased expression of the genes encoding TonB, alkaline protease,PrpL protease, exotoxin A, as well as fumarase C, Mn-dependent superoxide dismutase SodA, a ferredoxin and ferredoxin reductase and several oxidoreductases and dehydrogenases [6].
• In vivo, the kinetics of formation of this FpvA-PaA-Fe complex are more than two orders of magnitude faster than in vitro and depend on the presence of TonB [7].
• Unlike earlier studies with P. aeruginosa, we found that constitutive levels of gonococcal resistance to hydrophobic antimicrobial agents (i.e., Triton X-100 [TX-100]) did not require the TonB, ExbB, or ExbD protein [8].
• The in vivo growth ability and lethal virulence were also restored by introduction of the tonB-carrying plasmid in the tonB mutant [1].

Chemical compound and disease context of tonB

• TonB couples the energized state of the cytoplasmic membrane to the operation of outer membrane receptors responsible for Fe(III) siderophore uptake across the outer membrane of gram-negative bacteria [9].
• TonBp.a. showed substantially greater similarity to the Escherichia coli TonB protein than the Pseudomonas putida protein (31% identity vs. 20% identity) and tonBp.a. was able to complement deficiencies in the acquisition of ferric enterobactin and vitamin B12, and sensitivity to phage phi 80 of an E. coli tonB strain [10].

Biological context of tonB

• A tonB mutant of Pseudomonas aeruginosa deficient in iron siderophore uptake was shown in the present study to be hypersusceptible to a wide variety of antibiotics, reminiscent of the phenotype of mutants defective in the mexAB-oprM antibiotic efflux operon [9].
• Thus, TonB plays an important role in both intrinsic and acquired antibiotic resistance in P. aeruginosa [9].
• Targeting of the TonB1 fragment to the periplasm of P. aeruginosa inhibited the transport of ferric pyoverdine by FpvA in vivo, indicating an interference with endogenous TonB1, presumably caused by competition for binding sites at the transporter or by formation of nonfunctional TonB heterodimers [11].
• The cytotoxin (31,700 Mr) lacks an N-terminal signal sequence for bacterial secretion but contains a pentapeptide consensus sequence commonly found in prokaryotic proteins which function in a TonB-dependent manner [12].
• Neisserial TonB-dependent outer-membrane proteins: detection, regulation and distribution of three putative candidates identified from the genome sequences [13].

Associations of tonB with chemical compounds

• These results indicate clearly that the intact tonB gene-and, therefore, the TonB protein encoded by it-is essential for iron acquisition mediated by pyoverdin and pyochelin and via heme uptake in P. aeruginosa and suggest that the TonB-dependent iron acquisition may be essential for P. aeruginosa to infect the animal host [1].

Other interactions of tonB

• Similarly, elimination of tonB from an nfxB strain only partially compromised MexCD-OprJ-mediated multidrug resistance [9].
• The Pseudomonas aeruginosa tonB gene encodes a novel TonB protein [10].

Analytical, diagnostic and therapeutic context of tonB

• In addition, animal experiments showed that, in contrast to PAO1, the tonB mutant of PAO1 could not grow in vivo, such as in the muscles and lungs of immunosuppressed mice, and could not kill any of the animals [1].
• TonB proteins are essential components in iron-siderophore uptake in bacteria, apparently functioning as energy transducers in coupling the energized state of the cytoplasmic membrane to outer-membrane receptor function [10].

References