The Ribosome Is the Ultimate Receptor for Trypsin Modulating Oostatic Factor (TMOF)

Borovsky, Dov; Rougé, Pierre; Shatters, Robert G.

doi:10.3390/biom12040577

Cited by 5 publications

(5 citation statements)

References 39 publications

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“…These earlier reports indicate that in order for Aea TMOF or Neb TMOF to stop the translation of the trypsin message the peptides have to bind a gut receptor that allows it to enter the gut epithelial cells from the hemolymph and then bind the ribosome preventing the translation of the trypsin or chymotryspin transcripts as was recently shown for Ae . aegypti (Borovsky et al, 2021, 2022). To find out if H. virescens larvae have a similar receptor like was found for Ae.…”

Section: Discussionmentioning

confidence: 99%

Heliothis virescens chymotrypsin is translationally controlled by AeaTMOF binding ABC putative receptor

Borovsky

Rougé

2023

Arch Insect Biochem Physiol

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Heliothis virescens larval chymotrypsin (GenBank accession number AF43709) was cloned, sequenced and its three dimensional (3D) conformation modeled. The enzyme's transcript was first detected 6 days after larval emergence and the transcript level was shown to fall between larval ecdysis periods. Comparisons between the activities of larval gut chymotrypsin and trypsin shows that chymotrypsin activity is only 16% of the total trypsin activity and the pH optimum of the larval chymotrypsin is between pH 9−10, however the enzyme also exhibited a broad activity between pH 4−6. Injections of AeaTMOF and several shorter analogues into 3rd instar larvae followed by Northern blot analyses showed that although the chymotrypsins activities were inhibited by 60%−80% the transcript level of the sequenced chymotrypsin was not reduced and was similar to controls in which the chymotrypsin activity was not inhibited, indicating that AeaTMOF and its analogues exert a translational control. Based on these observations a putative AeaTMOF receptor (ABCC4) homologous to the Ae. aegypti ABC receptor sequence was found in the H. virescens genome. 3D molecular modeling and docking of the AeaTMOF and several of its analogues to the ABCC4 receptor showed that it can bind AeaTMOF and its analogues as was shown before for the Ae. aegypti receptor.

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Section: Discussionmentioning

confidence: 99%

Heliothis virescens chymotrypsin is translationally controlled by AeaTMOF binding ABC putative receptor

Borovsky

Rougé

2023

Arch Insect Biochem Physiol

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“…Indeed, E. coli cells, lacking the SbmA transporter, that were incubated with Aea TMOF and oncocin112 (1–13) were inhibited only in the presence of Aea TMOF (5 mM and 3 mM, respectively) ( Figure 5 A), whereas concentrations of oncocin112 (1–13) (10 mM and 20 mM) failed to fully inhibit the growth of these bacterial cells ( Figure 5 B) indicating that oncocin112 (1–13) uses SbmA exclusively to enter the E. coli cells, whereas Aea TMOF in the absence of SbmA can use other transporters such as MdtM, YjiL, or YgdD to enter the bacterial cells [ 20 ]. Our earlier reports [ 25 , 46 ] show that Aea TMOF is transported into the midgut epithelial cells of Ae. Aegypti by an ABC importer that uses ATP hydrolysis to transport Aea TMOF into the mosquito gut epithelial cells before it binds the mosquito ribosome, stopping trypsin biosynthesis [ 25 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…Our earlier reports [ 25 , 46 ] show that Aea TMOF is transported into the midgut epithelial cells of Ae. Aegypti by an ABC importer that uses ATP hydrolysis to transport Aea TMOF into the mosquito gut epithelial cells before it binds the mosquito ribosome, stopping trypsin biosynthesis [ 25 , 46 ]. To eliminate the possibility that Aea TMOF uses a similar transporter to enter E. coli cells, we incubated E. coli cells lacking the SbmA transporter in the presence of NaAzide (25 and 250 mM) to inhibit ATPase activity, thus inhibiting Aea TMOF-like ABC transporters in E. coli .…”

Section: Discussionmentioning

confidence: 99%

“…Aea TMOF is a proline-rich amphipathic decapeptide (YDPAPPPPPP) analogous to the PrAMP that was reported in insects and mammals that use the SbmA transporter to enter the bacterial cell, bind to the bacterial ribosome, and inhibit protein translation [ 21 , 22 , 23 , 24 ]. Because Aea TMOF is a proline-rich peptide and like onc112 also affects the translation of the mRNA by the ribosomes [ 25 ], we tested the possibility that Aea TMOF can be used as a novel antimicrobial agent against Gram-negative and -positive bacterial cells. We report here for the first-time in vivo studies and 3D modeling showing that Aea TMOF inhibits both Gram-positive and Gram-negative bacterial cell growth using SbmA as well as MdtM transporters [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Bactericidal Properties of Proline-Rich Aedes aegypti Trypsin Modulating Oostatic Factor (AeaTMOF)

Borovsky

Rougé

Shatters

2022

Life

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The antimicrobial properties of proline-rich Aedes aegypti decapeptide TMOF (AeaTMOF) and oncocin112 (1–13) were compared. Incubations with multidrug-resistant Escherichia coli cells showed that AeaTMOF (5 mM) was able to completely inhibit bacterial cell growth, whereas oncocin112 (1–13) (20 mM) partially inhibited bacterial growth as compared with bacterial cells that were not multidrug-resistant cells. AeaTMOF (5 mM) was very effective against Acinetobacter baumannii and Pseudomonas aeruginosa, completely inhibiting cell growth during 15 h incubations. AeaTMOF (5 mM) completely inhibited the Gram-positive bacteria Staphylococcus aureus and Bacillus thurengiensis sups. Israelensis cell growth, whereas oncocin112 (1–13) (10 and 20 mM) failed to affect bacterial cell growth. E. coli cells that lack the SbmA transporter were inhibited by AeaTMOF (5 mM) and not by oncocin112 (1–13) (10 to 20 mM), indicating that AeaTMOF can use other bacterial transporters than SbmA that is mainly used by proline-rich antimicrobial peptides. Incubation of E. coli cells with NaAzide showed that AeaTMOF does not use ABC-like transporters that use ATP hydrolysis to import molecules into bacterial cells. Three-dimensional modeling and docking of AeaTMOF to SbmA and MdtM transporters showed that AeaTMOF can bind these proteins, and the binding location of AeaTMOF inside these protein transporters allows AeaTMOF to be transported into the bacterial cytosol. These results show that AeaTMOF can be used as a future antibacterial agent against both multidrug-resistant Gram-positive and -negative bacteria.

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“…The peptide binds to a receptor on midgut epithelial cells, inhibiting trypsin-like enzyme production. The gut specific receptor of trypsin regulating oostatic factoris is ABCtmfA transporter which import the former into epithelial cells and the ultimate receptor is ribosomes which interfere in translation of trypsin mRNA transcript (Borovsky et al, 2022) [21] . TMOF concentration in the ovary does not increase significantly for 3-18 hours after a blood meal but increases rapidly to nearly twenty-fold for 18-48 hours.…”

Section: Aea-tmof Biosynthesis and Characterisationmentioning

confidence: 99%

Trypsin modulating oostatic factor and its application as a larvicide for mosquito control: A review

Meethal

2024

Int. J. Mosq. Res.

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Mosquitoes transmit diseases such as Dengue, Zika, Malaria, and Filariasis. Because of the development of resistance, traditional mosquito control measures are ineffective, and synthetic pesticides offer several environmental and health risks. As a result, alternative environmentally acceptable mosquito control technologies must be developed. TMOF (Trypsin Modulating Oostatic Factor) is an oostatic decapeptide, discovered in the ovaries of blood-fed female Aedes aegypti L. and prevents trypsin biosynthesis in their gut. TMOF isolated from A. aegypti (Aea-TMOF) has been shown to cause mortality in adults and larvae of several mosquito species in studies. It can be utilised as a natural bio-control agent. A comparable TMOF from the fleshfly Neobellieria bullata (Neb-TMOF) and another peptide, Neb-colloostatin, were discovered during the search for related folliculostatins in insects. Though chemically distinct to Aea-TMOF, the hexapeptide Neb-TMOF possesses prothoracicostatic action and is physiologically similar to Aea-TMOF. Neb-colloostatin influence egg development but do not affect trypsin biosynthesis. The gut receptor for Aea-TMOF has recently been cloned, produced, and described. In this review, we compare and contrast Aea-discovery, TMOF's structure, biosynthesis, expression in different organisms, and mosquito larvicidal action with Neb-TMOF. Finally, we talk about how TMOF and its counterparts could be used to control mosquitoes.

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The Ribosome Is the Ultimate Receptor for Trypsin Modulating Oostatic Factor (TMOF)

Cited by 5 publications

References 39 publications

Heliothis virescens chymotrypsin is translationally controlled by AeaTMOF binding ABC putative receptor

Heliothis virescens chymotrypsin is translationally controlled by AeaTMOF binding ABC putative receptor

Bactericidal Properties of Proline-Rich Aedes aegypti Trypsin Modulating Oostatic Factor (AeaTMOF)

Trypsin modulating oostatic factor and its application as a larvicide for mosquito control: A review

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