Involvement of multiple distinct Bordetella receptor proteins in the utilization of iron liberated from transferrin by host catecholamine stress hormones

Abstract

Summary Bordetella bronchiseptica is a pathogen that can acquire iron using its native alcaligin siderophore system, but can also use the catechol xenosiderophore enterobactin via the BfeA outer membrane receptor. Transcription of bfeA is positively controlled by a regulator that requires induction by enterobactin. Catecholamine hormones also induce bfeA transcription and B. bronchiseptica can use the catecholamine noradrenaline for growth on transferrin. In this study, B. bronchiseptica was shown to use catecholamines to obtain iron from both transferrin and lactoferrin in the absence of siderophore. In the presence of siderophore, noradrenaline augmented transferrin utilization by B. bronchiseptica, as well as siderophore function in vitro. Genetic analysis identified BfrA, BfrD and BfrE as TonB‐dependent outer membrane catecholamine receptors. The BfeA enterobactin receptor was found to not be involved directly in catecholamine utilization; however, the BfrA, BfrD and BfrE catecholamine receptors could serve as receptors for enterobactin and its degradation product 2,3‐dihydroxybenzoic acid. Thus, there is a functional link between enterobactin‐dependent and catecholamine‐dependent transferrin utilization. This investigation characterizes a new B. bronchiseptica mechanism for iron uptake from transferrin that uses host stress hormones that not only deliver iron directly to catecholamine receptors, but also potentiate siderophore activity by acting as iron shuttles.

Identificação de transcritos diferencialmente expressos por Pasteurella multocida em condições de privação de ferro

“…O perfil de transcritos superexpressos na condição de Fe -está associado a transoporte celular e proteínas de membrana que são descritos em P. multocida e outras bactérias. Os genes da família fbpABC, por exemplo, durante a privação de Fe em bactérias estão associados ao complexo tonB (Paustian et al 2001, Paustian et al 2002, que captura o Fe3+ da trasferrina para o espaço periplasmático bacteriano (Armstrong et al 2012). Estudos de expressão dos genes fbpABC em Neisseria miningitidis, demostraram que a transcrição de fbpA é aumentada em condições de limitação de Fe, além da interação acoplada de fbpAB e fbpBC no transporte de Fe periplasmático de transferrina e lactoferrina humana.…”

Interspecies Variations in Bordetella Catecholamine Receptor Gene Regulation and Function

“…B. parapertussis has bfrD and an apparent bfrE pseudogene; the ability of this species to use norepinephrine to obtain iron from transferrin was modest, and it was unable to use norepinephrine to obtain iron from lactoferrin. The bfrD and bfrE genes lie adjacent to each other on the Bordetella chromosome, and bfrD appears to have arisen by duplication of bfrE (20). The bfrD and bfrE nucleotide sequences are 56.7% similar (21), and the deduced proteins have 57.5% pairwise identity.…”

“…B. pertussis has apparently intact bfrD and bfrE genes; however, its ability to use catecholamines to obtain iron from either transferrin or lactoferrin has not yet been demonstrated successfully (20). B. parapertussis has bfrD and an apparent bfrE pseudogene; the ability of this species to use norepinephrine to obtain iron from transferrin was modest, and it was unable to use norepinephrine to obtain iron from lactoferrin.…”

“…Briefly, a bfrD bfrE deletion mutant was first constructed as described previously (20). bfrD and bfrE are adjacent to each other on the chromosome, and the mutation resulted in the removal of a 4,393-bp DNA segment spanning the genes.…”

“…Bordetella species also use heme iron sources (17)(18)(19). Recently, we found that B. bronchiseptica can use neuroendocrine catecholamine hormones, such as norepinephrine, to obtain iron from the host glycoproteins transferrin and lactoferrin (20). The TonB-dependent outer membrane receptor proteins BfrA, BfrD, and BfrE were each determined to be involved in catecholamine-mediated utilization of transferrin iron.…”