Dysgalacticin is a large (21.5 kDa), heat-labile bacteriocin that is active against the human pathogen Streptococcus pyogenes (Heng et al., 2006). It is bactericidal towards S. pyogenes and inhibits glucose fermentation by non-growing cell suspensions. Dysgalacticin blocked transport of both glucose and 2DG, indicating that dysgalacticin targets the phosphoenolpyruvate-dependent glucose- and mannose-phosphotransferase system (PTS) of S. pyogenes. This inhibitory activity was voltage-independent, and in addition to inhibiting glucose transport, dysgalacticin increased the permeability of the cytoplasmic membrane mediating leakage of intracellular potassium ions. Moreover, dysgalacticin dissipated the membrane potential and inhibited [¹⁴C]serine uptake, a membrane potential-dependent process in S. pyogenes (Swe et al., 2009). Swe et al. (2010) have identified a small (57aa) protein of 2 TMSs called DysI of S. dysgalactiae (ABY63615) that serves as a dysgalacticin immunity protein, protecting cells from the action of dysgalacticin.

Taken together, these observations indicate that dysgalacticin targets the glucose- and/or mannose-PTS as a receptor leading to inhibition of sugar uptake. Possibly as a result of this interaction, it perturbs membrane integrity leading to loss of intracellular K ions and dissipation of the membrane potential, ultimately leading to cell death (Swe et al., 2009).

8.B.18 The Glucose PTS Inhibitor Dysgalacticin (Dysgalacticin) Family Dysgalacticin is a large (21.5 kDa), heat-labile bacteriocin that is active against the human pathogen Streptococcus pyogenes (Heng et al., 2006). It is bactericidal towards S. pyogenes and inhibits glucose fermentation by non-growing cell suspensions. Dysgalacticin blocked transport of both glucose and 2DG, indicating that dysgalacticin targets the phosphoenolpyruvate-dependent glucose- and mannose-phosphotransferase system (PTS) of S. pyogenes. This inhibitory activity was voltage-independent, and in addition to inhibiting glucose transport, dysgalacticin increased the permeability of the cytoplasmic membrane mediating leakage of intracellular potassium ions. Moreover, dysgalacticin dissipated the membrane potential and inhibited [¹⁴C]serine uptake, a membrane potential-dependent process in S. pyogenes (Swe et al., 2009). Swe et al. (2010) have identified a small (57aa) protein of 2 TMSs called DysI of S. dysgalactiae (ABY63615) that serves as a dysgalacticin immunity protein, protecting cells from the action of dysgalacticin. Taken together, these observations indicate that dysgalacticin targets the glucose- and/or mannose-PTS as a receptor leading to inhibition of sugar uptake. Possibly as a result of this interaction, it perturbs membrane integrity leading to loss of intracellular K ions and dissipation of the membrane potential, ultimately leading to cell death (Swe et al., 2009).
References:
Heng, N.C., N.L. Ragland, P.M. Swe, H.J. Baird, M.A. Inglis, J.R. Tagg, and R.W. Jack. (2006). Dysgalacticin: a novel, plasmid-encoded antimicrobial protein (bacteriocin) produced by Streptococcus dysgalactiae subsp. equisimilis. Microbiology 152: 1991-2001. 16804174
Swe, P.M., G.M. Cook, J.R. Tagg, and R.W. Jack. (2009). Mode of action of dysgalacticin: a large heat-labile bacteriocin. J Antimicrob Chemother 63: 679-686.
Swe, P.M., N.C. Heng, G.M. Cook, J.R. Tagg, and R.W. Jack. (2010). Identification of DysI, the immunity factor of the streptococcal bacteriocin dysgalacticin. Appl. Environ. Microbiol. 76: 7885-7889.
Examples:
TC#	Name	Organismal Type	Example
8.B.18.1.1	The 3 TMS bacteriocin, dysgalacticin, DysA2 or DysA	Bacteria	*DysA2 of Streptococcus dysgalactiae* (A9UL24)**

8.B.18.1.2	Uncharacterized protein of 196 aas and 3 TMSs, one N-terminal and two C-terminal.		UP of Streptococcus equi

8.B.18.1.3	Uncharacterized protein of 126 aas and 1 N-terminal TMS.		*UP of Pseudoalteromonas* sp.**

8.B.18.1.4	Uncharacterized protein of 100 aas and 1 N-terminal TMS.		UP of Enterococcus durans

8.B.18.1.5	Uncharacterized protein of 196 aas and 1 or 2 TMSs, one N-terminal, and possibly one C-terminal.		*UP of Dokdonia* sp.**