4.A.3 The PTS Lactose-N,N'-Diacetylchitobiose-β-glucoside (Lac) Family The Lac family includes several sequenced lactose (β-galactoside) porters of Gram-positive bacteria as well as the E. coli and Borrelia burgdorferi N,N'-diacetylchitobiose (Chb) porters. The former can transport aromatic β-glucosides and cellobiose as well as the chitin disaccharide, Chb. However, only Chb induces expression of the chb operon. While the Lac porters consist of two polypeptide chains (IIA and IICB), the Chb porters of E. coli and B. burgdorferi consist of three (IIA, IIB and IIC). In E. coli, the IIA^Chb protein has been shown to form a stable dimer both when phosphorylated and when unphosphorylated. The IIC domains of these permeases are believed to have a uniform topology with 10 TMSs (Cao et al. 2011; Vastermark and Saier 2016). In E. coli, the IIB^Chb is a monomer. Two IIB^Chb monomers associate with the IIA^Chb dimer. The structure of the IIB domain of the Chb porter has been determined both by NMR and by x-ray crystallography. It exhibits an α/β doubly wound superfold. This is different from the structure of the IIB^Glc and IIB^Man domains. IIB^Sgc, believed to function in pentose transport, is homologous to IIB^Lac and IIB^Chb. In B. subtilis, a PTS porter similar to the Chb porter of E. coli is believed to transport lichenan (a β-1,3;1,4 glucan) degradation products, oligosaccharides of 2-4 glucose units. The B. burgdorferi system is more similar to the Bacillus Lic system than the E. coli Chb system. The IIC domains of members of the Lac family are all more similar to each other than they are to those of the Glc, Bgl, Fru and Mtl families.
This family belongs to the PTS-GFL Superfamily.
References:
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Cao, T.N., P. Joyet, F.M.D. Aké, E. Milohanic, and J. Deutscher. (2019). Studies of the Listeria monocytogenes Cellobiose Transport Components and Their Impact on Virulence Gene Repression. J. Mol. Microbiol. Biotechnol. 29: 10-26.
Cao, Y., X. Jin, E.J. Levin, H. Huang, Y. Zong, M. Quick, J. Weng, Y. Pan, J. Love, M. Punta, B. Rost, W.A. Hendrickson, J.A. Javitch, K.R. Rajashankar, and M. Zhou. (2011). Crystal structure of a phosphorylation-coupled saccharide transporter. Nature 473: 50-54.
Chen, C., M. Zhang, Y. Zhang, X. Jiang, J. Kong, J. Zhou, G. Huang, R. Zhang, H. Li, and Z. Gui. (2025). Genomic and transcriptomic insights into the cellulose-degrading mechanism of Bacillus subtilis DC-11 and its novel cellulose catabolic pathway. Arch. Microbiol. 207: 158.
Combret, V., I. Rincé, R. Cochelin, F. Desriac, C. Muller, D. Soussan, A. Hartke, J. Deutscher, and N. Sauvageot. (2025). Cellodextrin Metabolism and Phosphotransferase System-Catalyzed Uptake in Enterococcus faecalis. Mol. Microbiol. 123: 378-391.
Francl, A.L., J.L. Hoeflinger, and M.J. Miller. (2012). Identification of lactose phosphotransferase systems in Lactobacillus gasseri ATCC 33323 required for lactose utilization. Microbiology 158: 944-952.
Hall, B.G., K. Imai, and C.P. Romano. (1982). Genetics of the lac-PTS system of Klebsiella. Genet Res 39: 287-302.
Imai, K. and B.G. Hall. (1981). Properties of the lactose transport system in Klebsiella sp. strain CT-1. J. Bacteriol. 145: 1459-1462.
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Keyhani, N.O. and S. Roseman. (1997). Wild-type Escherichia coli grows on the chitin disaccharide N,N'-diacetylchitobiose, by expressing the cel operon. Proc. Natl. Acad. Sci. USA 94: 14367-14371.
Keyhani, N.O., K. Bacia, and S. Roseman. (2000). The transport/phosphorylation of N,N'-diacetylchitobiose in Escherichia coli. J. Biol. Chem. 275: 33102-33109.
Keyhani, N.O., L.X. Wang, Y.C. Lee, and S. Roseman. (2000). The chitin disaccharide, N,N'-diacetylchitobiose, is catabolized by Escherichia coli and is transported/phosphorylated by the phosphoenolpyruvate: glycose phosphotransferase system. J. Biol. Chem. 275: 33084-33090.
Keyhani, N.O., M.E. Rodgers, B. Demeler, J.C. Hansen, and S. Roseman. (2000). Analytical sedimentation of the IIA^Chb and IIB^Chb proteins of the Escherichia coli N,N'-diacetylchitobiose phosphotransferase system. J. Biol. Chem. 275: 33110-33115.
Keyhani, N.O., O. Boudker, and S. Roseman. (2000). Isolation and characterization of IIA^Chb, a soluble protein of the enzyme II complex required for the transport/phosphorylation of N,N'-diacetylchitobiose in Escherichia coli. J. Biol. Chem. 275: 33091-33101.
Kowalczyk, M., M. Cocaign-Bousquet, P. Loubiere, and J. Bardowski. (2008). Identification and functional characterisation of cellobiose and lactose transport systems in Lactococcus lactis IL1403. Arch. Microbiol. 189(3): 187-196.
Kowolik, C.M. and W. Hengstenberg. (1998). The lactose transporter of Staphylococcus aureus--overexpression, purification and characterization of the histidine-tagged domains IIC and IIB. Eur J Biochem 257: 389-394.
Meibom, K.L., X.B. Li, A.T. Nielsen, C.Y. Wu, S. Roseman, and G.K. Schoolnik. (2004). The Vibrio cholerae chitin utilization program. Proc. Natl. Acad. Sci. USA 101: 2524-2529.
Nguyen, T.X., M.R. Yen, R.D. Barabote, and M.H. Saier, Jr. (2006). Topological predictions for integral membrane permeases of the phosphoenolpyruvate:sugar phosphotransferase system. J. Mol. Microbiol. Biotechnol. 11: 345-360.
Reizer, J., A. Charbit, A. Reizer, and M.H. Saier, Jr. (1996). Novel phosphotransferase system genes revealed by bacterial genome analysis: Operons encoding homologues of sugar-specific permease domains of the phosphotransferase system and pentose catabolic enzymes. Genome Sci. Technol. 1: 53-75.
Reizer, J., S. Bachem, A. Reizer, M. Arnaud, M.H. Saier, Jr., and J. Stülke. (1999). Novel phosphotransferase system genes revealed by genome analysis – the complete complement of PTS proteins encoded within the genome of Bacillus subtilis. Microbiology 145: 3419-3429.
Rosey, E.L. and G.C. Stewart. (1992). Nucleotide and deduced amino acid sequences of the lacR, lacABCD, and lacFE genes encoding the repressor, tagatose 6-phosphate gene cluster, and sugar-specific phosphotransferase system components of the lactose operon of Streptococcus mutans. J. Bacteriol. 174: 6159-6170.
Sadaie, Y., H. Nakadate, R. Fukui, L.M. Yee, and K. Asai. (2008). Glucomannan utilization operon of Bacillus subtilis. FEMS Microbiol. Lett. 279: 103-109.
Tilly, K., A.F. Elias, J. Errett, E. Fischer, R. Iyer, I. Schwartz, J.L. Bono, and P. Rosa. (2001). Genetics and regulation of chitobiose utilization in Borrelia burgdorferi. J. Bacteriol. 183: 5544-5553.
Tobisch, S., P. Glaser, S. Krüger, and M. Hecker. (1997). Identification and characterization of a new β-glucoside utilization system in Bacillus subtilis. J. Bacteriol. 179: 496-506.
Toratani, T., T. Shoji, T. Ikehara, K. Suzuki, and T. Watanabe. (2008). The importance of chitobiase and N-acetylglucosamine (GlcNAc) uptake in N,N'-diacetylchitobiose [(GlcNAc)2] utilization by Serratia marcescens 2,170. Microbiology 154: 1326-1332.
Van Montfort, R.L.M., T. Pijning, K.H. Kalk, J. Reizer, M.H. Saier, Jr., M.M.G.M. Thunnissen, G.T. Robillard, and B.W. Dijkstra. (1997). The structure of an energy-coupling protein from bacteria, IIB^cellobiose, reveals similarity to eukaryotic protein tyrosine phosphatases. Structure 5: 217-225.
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Examples:
TC#	Name	Organismal Type	Example
4.A.3.1.1	Lactose (Lac) porter, LacEF (Kowolik and Hengstenberg 1998). This system is 87% identical to the LacEF ortholog in Streptococcus mutans (Rosey and Stewart 1992).	Bacteria	Lactose (Lac) IICB-IIA complex of Staphylococcus aureus IIA (LacF) (P02909) IIBC (LacE) (P11162)

4.A.3.1.2	*Lactose PTS group translocator #1, IIA/IICB (Francl et al.* 2012).**	Firmicutes	Lactose PTS porter #1of Lactobacillus gasseri

4.A.3.1.3	*Lactose PTS group translocator #2, IIA/IICB (Francl et al.* 2012).**	Firmicutes	Lactose PTS porter #2 of Lactobacillus gasseri

Examples:
TC#	Name	Organismal Type	Example
4.A.3.2.1	*N,N'-diacetylchitobiose (Chb) porter (also transports cellobiose; Kachroo et al., 2007).*	Bacteria	N,N'-diacetylchitobiose (Chb) IIC-IIB-IIA complex of E. coli IIA (ChbA), spP17335 IIB (ChbB), spP17409 IIC (ChbC), spP17334

4.A.3.2.10	Oligo β-(gluco)mannoside (derived from (gluco)mannan))-specific PTS transporter, GmuABC (YdhNMO). The glucomannan utilization operon (gmuBACDREFG, formerly ydhMNOPQRST) of Bacillus subtilis has been characterized (Sadaie et al. 2008). Transcription of the operon is induced by konjac glucomannan and requires the last mannanase gene (gmuG). Cellobiose and mannobiose, possible degradation products of glucomannan by GmuG, are strong inducers of transcription. An internal regulatory gene (gmuR) encodes a repressor of the operon, as disruption of this gene enhances transcription of the operon in the absence of inducers. The expression of the glucomannan utilizing operon is thus induced by degraded glucomannan products, and repressed by an internal repressor (Sadaie et al. 2008). This system is induced by the presence of cellobiose in the growth medium (Chen et al. 2025).		GmuABC of Bacillus subtilis GmuA, IIA, 110 aas, O05506 GmuB, IIB, 103 aas, O05505 GmuC, IIC, 422 aas and 10 TMSs, O05507

4.A.3.2.11	Cellobiose PTS transporter with one IIC protein, CelC1, of 435 aas and 10 predicted TMSs(Q8Y3Z4, and two sets of IIAB proteins, CelA1 (100 aas; Q927F6) and CelB1 (101 aas; Q8Y3Z5) as well as CelA2 (100 aas; Q92AT9) and CelB2 (102 aas; Q8Y6G7). Another IIC-like protein was also found (454 aas; 10 TMSs; Q8Y3X1) but it did not phosphorlyate cellobiose, and its function was not identified. Transcription of these genes is regulated by CelR (Cao et al. 2019). UniProt acc#s for CelB1, CelA1 and CelC1 of E. faecalis are, respectively, Q836U0, Q836T9 and Q836T8.		CelA1/A2/B1/B2/C1 of Listeria monocytogenes

4.A.3.2.12	PTS gentiobiose (glucosyl β-1,6-glucose) transporter, subunit IIC of 444 aas and 10 TMSs. May also transport several other beta-glucosides including inaribiose (β-1,3), chitobiose (NAcGlu-β-1,4), N(4)-β-Nacetyl-D-glucosaminyl-L-Asn (asparagine), chitobiose (NAG-β-1,4-NAG) and sophorose (β-1,2) (Combret et al. 2025). This PTS system is under the control of CelR, a LevR-like transcriptional activator (Combret et al. 2025). It uses IIA and IIB proteins from another PTS transporter, CelA1 and CelB1 (see TC# 4.A.3.2.13).		GenB (IIC^Gen) of Enterococcus faecalis

4.A.3.2.13	Cellobiose PTS Enzyme IIC, IIA and IIB, Cel1C, Cel1A and Cel1B, respectively. Cel1C has 425 aas and 10 predicted TMSs (Combret et al. 2025). This system is the dominant cellobiose uptake system in E. faecalis.		CelCAB of Enterococcus faecalis

4.A.3.2.14	PTS transporter, IICAB2^cel. IIC has 487 aas and 10 predicted TMSs. This system transports cellobiose, cellotriose, and cellotetraose, and possible higher MW oligosaccharides in this series. It has its own IIB protein but uses the IIA protein of the Cel1 system (TC# 4.A.3.2.13) (Combret et al. 2025). In addition to IIC, IIA and IIB, three additional proteins seem to be required for function, although what these biochemical functions are is not known. These proteins are designated CelG (73 aas), CelH (67 aas) and CelI (137 aas) and are the last three proteins included in this system in TCDB (see Combret et al. 2025 for more details). UniProt acc #s for CelB2, CelC2, CelG, CelH and CelI of E. faecalis are Q836U5, Q836U4, Q836U3, Q836U2, and Q836U1, respectively.		IICAB2^Cel of Enterococcus faecalis

4.A.3.2.2	Lichenan oligosaccharide (Lic) porter: LicA-LicB-LicC of 110, 102 and 452 aas, respectively. Functions with LicH, a P-β-glucosidase (P46320).	Bacteria	Lichenan oligosaccharide (Lic) IIC-IIB-IIA complex of Bacillus subtilis IIA (LicA), spP46319 IIB (LicB), spP46318 IIC (LicC), spP46317

4.A.3.2.3	N,N'-diacetylchitobiose porter, ChbABC	Bacteria	N,N'diacetylchitobiose (Chb) IIC-IIB-IIA complex of Borrelia burgdorferi IIA (ChbA), AAC66323 IIB (ChbB), AAC66322 IIC (ChbC), AAC66324

4.A.3.2.4	*The cellobiose-specific (PtcA-PtcB-CelB) porter (Kowalczyk et al., 2008 ).*	Bacteria	PtcA-PtcB-CelB of Lactococcus lactis: CelB (C)(Q9CJ32) PtcB (B)(Q9CIF0) PtcA (A)(Q9CIE9)

4.A.3.2.5	The N,N' -diacetylchitobiose Enzyme II (Toratani et al., 2008) (>80% identical to the E. coli enzyme (4.A.3.2.1)). The IIA protein is the Serratia glucose IIA which is nearly identical to the E. coli IIA^Glc (Crr).	Proteobacteria	The N,N' -diacetylchitobiose Enzyme II of Serratia marcescens IIA (ChbA) - Q8L3C4 IIB (ChbB) - Q8L3C3 IIC (ChbC) - Q8L3C2

4.A.3.2.6	*Glucosamine β(1→4) glucosamine (GlcN)₂ (glucosamine dimer) transporter, VC1281-1283 (IIB; IIC; IIA, respectively) (Meibom et al., 2004)*	Proteobacteria	(GlcN)₂ transporter of Vibrio cholerae (IIA-IIB-IIC) IIB (Q9KSH5) IIA (Q9KSH3) IIC (Q9KSH4)

4.A.3.2.7	N,N'-diacetylchitobiose (cellobiose) PTS permease, CelABC (IIABC). Essential for normal virulence and biofilm formation by K. pneumoniae which causes pyogenic liver abscesses (Wu et al. 2012). 88% identical to the diacetylchitobiose II (4.A.3.2.1) of E. coli. These two proteins are probably orthologous.	Proteobacteria	CelABC of Klebsiella pneumoniae

4.A.3.2.8	N-, N'-diacetylchitobiose PTS permease, IIABC^Chb (Also called IIABC^Cel for cellbiose). The crystal structure of the 10 TMS IIC membrane component has been determined by x-ray crystallography (Cao et al. 2011).	Firmicutes	ChbIIABC of Bacillus cereus ChbA (CelA); IIB (100 aas) (Q72XP9) ChbB (CelB); IIC (433 aas) (Q72XQ0) ChbC (CelC); IIA (106 aas) (Q72XQ1)

4.A.3.2.9	*PTS-type lactose transporter, IIC-IIB-IIA (Imai and Hall 1981; Hall et al.* 1982).**	Proteobacteria	Lactose permease of Klebsiella pneumoniae