Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins

Kalb, Suzanne R.; Baudys, Jakub; Smith, Theresa J.; Smith, Leonard A.; Barr, John R.

doi:10.3390/toxins9060193

Cited by 16 publications

(17 citation statements)

References 26 publications

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“…In several studies, no stable complex of BoNT/ A2 with any OrfX-protein has been found. Only the M-PTC consisting of BoNT and NTNH has been identified [2,26,52]. This was also the case in this study using recombinant proteins (Fig.…”

Section: Orfx Cluster General Discussionsupporting

confidence: 74%

“…OrfX2, OrfX3, and P47 have been shown to be expressed in cell cultures of Clostridium botulinum A2 Kyoto [2]. For the HA cluster of BoNT/A1, it has been shown that the growth media and culture condition play a role in what type of complex is formed from the NAPs [15,53,54], and a similar situation could be the case for the OrfX cluster of BoNT/A2 [26].…”

Section: Orfx Cluster General Discussionmentioning

confidence: 89%

“…1) [17]. For the HA cluster of BoNT/A1, it has been shown that the growth media and culture condition play a role in what type of complex is formed from the NAPs [15,53,54], and a similar situation could be the case for the OrfX cluster of BoNT/A2 [26]. In several studies, no stable complex of BoNT/ A2 with any OrfX-protein has been found.…”

Section: Orfx Cluster General Discussionmentioning

confidence: 99%

“…However, previously nothing was known regarding the structure or function of these proteins [8,17]. Recent studies indicate that the proteins can form a complex under certain conditions [26].…”

mentioning

confidence: 99%

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Crystal structures of OrfX2 and P47 from a Botulinum neurotoxin OrfX‐type gene cluster

et al. 2017

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Botulinum neurotoxins are highly toxic substances and are all encoded together with one of two alternative gene clusters, the HA or the OrfX gene cluster. Very little is known about the function and structure of the proteins encoded in the OrfX gene cluster, which in addition to the toxin contains five proteins (OrfX1, OrfX2, OrfX3, P47, and NTNH). We here present the structures of OrfX2 and P47, solved to 2.1 and 1.8 Å, respectively. We show that they belong to the TULIP protein superfamily, which are often involved in lipid binding. OrfX1 and OrfX2 were both found to bind phosphatidylinositol lipids.

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Section: Orfx Cluster General Discussionsupporting

confidence: 74%

Section: Orfx Cluster General Discussionmentioning

confidence: 89%

Section: Orfx Cluster General Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Crystal structures of OrfX2 and P47 from a Botulinum neurotoxin OrfX‐type gene cluster

et al. 2017

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“…Finally, the toxin gene is expressed along with several other toxin cluster genes as part of a botulinum toxin complex. The toxin-associated genes are known as either the hemagglutinin ( ha+ ) cluster or orfX ( orfX+ ) cluster, and are associated with different toxin types: BoNT/A, /B, /C, /D and /G are associated with HA complex proteins, while BoNT/A, /E and /F are associated with one or more orfX proteins [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Proteomic analysis of four Clostridium botulinum strains identifies proteins that link biological responses to proteomic signatures

et al. 2018

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Microorganisms alter gene and protein expression in response to environmental conditions to adapt and survive. Whereas the genetic composition of a microbe represents an organism’s biological potential, the proteins expressed provide a functional readout of the organism’s response to the environment. Understanding protein expression patterns in response to specific environmental conditions furthers fundamental knowledge about a microbe, which can be especially useful for understudied organisms such as Clostridium botulinum examined herein. In addition, protein expression patterns that reproducibly occur in certain growth conditions hold potential in fields such as microbial forensics, in which determination of conditions in which an unknown possible biothreat sample had been grown may be important. To investigate the identity and reproducibility of protein profile patterns for varied strains, we defined the proteomic profiles of four Group I strains of Clostridium botulinum, a Category A biothreat agent and the organism responsible for the production of the botulinum neurotoxin (BoNT), in two different culture media grown for five days. The four C. botulinum strains produced one of three neurotoxins (BoNT/A, /B, or /F), and their protein profiles were compared to that of a fifth non-toxigenic strain of C. sporogenes. These strains each had DNA sequences available to assist in accurate protein identification. Differing culture growth phase, bacterial strain, and growth medium resulted in reproducible protein profiles, which were used to calculate relative protein abundance ratios as an internally normalized metric of microbial growth in varying conditions. The resulting protein profiles provide functional information about how four Group I C. botulinum strains and a C. sporogenes strain respond to the culture environment during growth and explores the feasibility of using these proteins to characterize unknown samples.

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Crystal structures of OrfX1, OrfX2 and the OrfX1–OrfX3 complex from the orfX gene cluster of botulinum neurotoxin E1

et al. 2023

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Botulinum neurotoxins (BoNTs) are among the most lethal toxins known to humans, comprising seven established serotypes termed BoNT/A-G encoded in two types of gene clusters (ha and orfX) in BoNT-producing clostridia. The ha cluster encodes four non-toxic neurotoxin-associated proteins (NAPs) that assemble with BoNTs to protect and enhance their oral toxicity. However, the structure and function of the orfX-type NAPs remain largely unknown. Here, we report the crystal structures for OrfX1, OrfX2, and an OrfX1-OrfX3 complex, which are encoded in the orfX cluster of a BoNT/ E1-producing Clostridium botulinum strain associated with human foodborne botulism. These structures lay the foundation for future studies on the potential roles of OrfX proteins in oral intoxication and pathogenesis of BoNTs.

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Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins

Cited by 16 publications

References 26 publications

Crystal structures of OrfX2 and P47 from a Botulinum neurotoxin OrfX‐type gene cluster

Crystal structures of OrfX2 and P47 from a Botulinum neurotoxin OrfX‐type gene cluster

Proteomic analysis of four Clostridium botulinum strains identifies proteins that link biological responses to proteomic signatures

Crystal structures of OrfX1, OrfX2 and the OrfX1–OrfX3 complex from the orfX gene cluster of botulinum neurotoxin E1

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