1.C.130. The Membrane Potential-dispersing Orphan 10 Toxin, (OrtT) Family OrtT (YdcX), of 57 aas and 2 TMSs, is important for maintaining cell fitness during stress related to the stringent response (decreased amino acid, purine and thymidine availability). Overexpression inhibits cell growth, increases the formation of persister cells, and causes 99.9% of cells to undergo bacterial lysis within 2 hours after induction. Nucleoids condense, the cytoplasm seems empty and the periplasmic space enlarges. The intracellular ATP level decreases about 30-fold suggesting that the membrane potential may be disrupted (Islam et al. 2015). Although this protein is homologous to GhoT, the toxic component of a type IV toxin-antitoxin system, no antitoxin has been found. GhoS (the antitoxin for GhoT), YdcY (the neighboring gene), 5'- and 3'-UTRs as well as approximately 620 bp lengths of the BW25113 genome DNA were tested (Islam et al. 2015). The C-terminal (CT) toxin domains of contact-dependent growth inhibition (CDI) CdiA proteins target Gram-negative bacteria and must breach both the outer and inner membranes of target cells to exert growth inhibitory activity. It crosses the inner membrane via the SecY general secretory pathway (3.A.5.1.1) (Jones et al. 2021).
References:
Cheng, H.Y., V.W. Soo, S. Islam, M.J. McAnulty, M.J. Benedik, and T.K. Wood. (2014). Toxin GhoT of the GhoT/GhoS toxin/antitoxin system damages the cell membrane to reduce adenosine triphosphate and to reduce growth under stress. Environ Microbiol 16: 1741-1754.
Islam, S., M.J. Benedik, and T.K. Wood. (2015). Orphan toxin OrtT (YdcX) of Escherichia coli reduces growth during the stringent response. Toxins (Basel) 7: 299-321.
Jones, A.M., P. Virtanen, D. Hammarlöf, W.J. Allen, I. Collinson, C.S. Hayes, D.A. Low, and S. Koskiniemi. (2021). Genetic Evidence for SecY Translocon-Mediated Import of Two Contact-Dependent Growth Inhibition (CDI) Toxins. mBio 12:.
Wang, X., D.M. Lord, H.Y. Cheng, D.O. Osbourne, S.H. Hong, V. Sanchez-Torres, C. Quiroga, K. Zheng, T. Herrmann, W. Peti, M.J. Benedik, R. Page, and T.K. Wood. (2012). A new type V toxin-antitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS. Nat Chem Biol 8: 855-861.
Examples:
TC#	Name	Organismal Type	Example
Examples:
TC#	Name	Organismal Type	Example
1.C.130.1.1	The membrane potential-dissipating orphan 10 toxin, Ort10 or YdcX of 57 aas and 2 TMSs (Islam et al. 2015; Jones et al. 2021). See family description for details. It may form a H⁺-conducting channel, but this is not established.		OrtT of E. coli

1.C.130.1.2	Toxin GHoT of 57 aas and 2 TMSs. GhoT is the toxic component of a type V toxin-antitoxin (TA) system. It causes membrane damage when induced by MqsR, slowing cell growth and increasing the formation of dormant persister cells. It is involved with GhoS, its antitoxin, in reducing cell growth during antibacterial stress (Cheng et al. 2014). Overexpression causes cell lysis, forming ghost cells; both effects are neutralized by expression of GhoS. Overexpression in the presence of ampicillin increases persister cell formation (persister cells exhibit antibiotic tolerance without genetic change) (Wang et al. 2012). Overexpression causes about 90-fold reduction in cellular ATP levels and dissipates the membrane potential (Cheng et al. 2014).		GhoT of E. coli

1.C.130.1.3	GhoT/OrtT family toxin of 61 aas and 2 TMSs.		Toxin of Hafnia paralvei

1.C.130.1.4	GhoT/OrtT family toxin of 61 aas and 2 TMSs.		Toxin of Obesumbacterium proteus