. Author manuscript; available in PMC: 2014 Dec 4.

Published in final edited form as: Crit Rev Biochem Mol Biol. 2014 Mar 10;49(4):269–293. doi: 10.3109/10409238.2014.895700

Table.

Mtb genes associated with cholesterol metabolism or its regulons.^a

Mtb H37Rv Gene Ref^b	M. smegmatis ortholog gene number	Gene Name	Enzyme Function	Function Biochemically Validated (☑) Biochemically Predicted (□) Computation Annotated (?)	Gene Regulation and Essentiality

					Mtb Transcript Up-Regulated by Chol^c	Gene Required for Growth on Chol^d	Transcript Up-Regulated^e^,^f or Required for Growth^g In Macroϕ	Requiredfor Survival in Mice^h	Transcript Repressorⁱ
Rv0138	MSMEG_6475		conserved hypothetical protein	?					KstR1
Rv0139	MSMEG_6474		oxidoreductase	?					KstR1
Rv0162c	MSMEG_0217	adhE1	alcohol dehydrogenase	?					KstR1
Rv0223c	MSMEG_0309		Aldehyde dehydrogenase	?	✓				KstR1
Rv0244c	MSMEG_0406	fadE5	acyl-CoA dehydrogenase	?	✓	✓	Induced
Rv0468	MSMEG_0912	fadB2	3-hydroxyacyl-CoA dehydrogenase	☑	✓		Induced
Rv0551c	MSMEG_1098	fadD8	fatty acyl-CoA synthetase	?	✓				KstR1
Rv0687	MSMEG_1410			?	✓			Essential	KstR1
Rv0926c	MSMEG_5586		conserved hypothetical protein	?					KstR1
Rv0927c	MSMEG_5584		short-chain type dehydrogenase/reductase	?					KstR1
Rv0940c	MSMEG_5555		oxidoreductase	?	✓				KstR1
Rv0953c	MSMEG_5520		oxidoreductase	?	✓				KstR1
Rv1059	MSMEG_5286	dapB	dihydrodipicolinate reductase	?					KstR1
Rv1071c	MSMEG_5276	echA9	enoyl-CoA hydratase	?		✓	Induced
Rv1106c	MSMEG_5228	3β-hsd	3β-hydroxy steroid dehydrogenase	☑					KstR1 (only in M. smeg)
Rv1132	MSMEG_5202		conserved membrane protein	?			Induced		KstR1
Rv1193	MSMEG_5114	fadD36	fatty acyl-CoA synthetase	?		✓
Rv1323	MSMEG_4920	fadA4	thiolase	?			Essential	Essential
Rv1426c	MSMEG_0302	lipO	esterase	?					KstR1
Rv1427c	MSMEG_0304	fadD12	fatty acyl-CoA synthetase	?					KstR1
Rv1428c	MSMEG_0305		conserved hypothetical protein	?					KstR1
Rv1627c	MSMEG_3844		non-specific lipid transfer protein	?	✓				KstR1
Rv1628c	MSMEG_3843		conserved hypothetical protein	?	✓		Induced		KstR1
Rv1715	MSMEG_6791	fadB3	3-hydroxyacyl-CoA dehydrogenase	?			Induced
Rv1894c	MSMEG_3519		conserved hypothetical protein	?	✓		Induced		KstR1
Rv1912c	-	fadB5	3-hydroxyacyl-CoA dehydrogenase	?			Induced
Rv1930c	MSMEG_1107		conserved hypothetical protein	?				Essential	Mce3R
Rv1931c	MSMEG_1106		transcriptional regulator	?				Essential	Mce3R
Rv1933c	-	fadE18	steroid acyl-CoA dehydrogenase β subunit	□					Mce3R
Rv1934c	-	fadE17	steroid acyl-CoA dehydrogenase α subunit	□	✓		Induced		Mce3R
Rv1935c	-	echA13	enoyl-CoA hydratase	?	✓		Induced		Mce3R
Rv1936	-		monooxygenase	?	✓		Induced		Mce3R
Rv1937	-		electron transfer oxygenase	?	✓				Mce3R
Rv1938	-	ephB	epoxide hydrolase	?	✓				Mce3R
Rv1939	-		FMN oxidoreductase	?	✓		Induced	Essential	Mce3R
Rv1940	-	ribA1	bifunctional enzyme: GTP cyclohydrolase II and	?	✓				Mce3R
Rv1941	-		short-chain dehydrogenase	?	✓				Mce3R
Rv1942c	-		conserved hypothetical protein,	?			Induced		Mce3R
Rv1943c	-		conserved hypothetical protein,	?					Mce3R
Rv1963c	-	mce3R	transcriptional repressor (TetR-like)	☑		✓
Rv1964	-	yrbE3A	Mce-family	?	✓				Mce3R
Rv1965	MSMEG_0345	yrbE3B	Mce-family	?	✓				Mce3R
Rv1966	MSMEG_0346	mce3A	Mce-family	?	✓				Mce3R
Rv1967	MSMEG_0347	mce3B	Mce-family	?					Mce3R
Rv1970	MSMEG_0350	lprM	Mce-family lipoprotein LprM (Mce3E)	?			Induced		Mce3R
Rv1971	MSMEG_0351	mce3F	Mce-family	?					Mce3R
Rv1972	MSMEG_0352, MSMEG_5208		Mce-associated	?			Induced		Mce3R
Rv1973	MSMEG_0353		Mce-associated	?			Induced		Mce3R
Rv1975	MSMEG_0355		protein expressed in hypoxia	?			Induced		Mce3R
Rv2668	MSMEG_2790		conserved hypothetical protein	?	✓	✓			KstR1
Rv2669	MSMEG_2789		conserved hypothetical protein	?					KstR1
Rv2799	MSMEG_2645		membrane protein	?		✓			KstR1
Rv2800	MSMEG_2644		conserved hypothetical protein	?					KstR1
Rv3139	MSMEG_2081	fadE24	steroid acyl-CoA dehydrogenase β subunit	□	✓		Induced		sigE
Rv3140	MSMEG_2080	fadE23	steroid acyl-CoA dehydrogenase α subunit	□	✓		Induced		sigE
Rv3141	MSMEG_2033	fadB4	3-hydroxyacyl-CoA dehydrogenase	?
Rv3492c	MSMEG_5893		conserved hypothetical protein	?		✓			KstR1
Rv3493c	MSMEG_5894		conserved hypothetical protein	?		✓			KstR1
Rv3494c	MSMEG_5895	mce4F	mce4 operon: lipid transfer	☑		✓			KstR1
Rv3495c	MSMEG_5896	mce4E	mce4 operon: lipid transfer	☑		✓		Essential	KstR1
Rv3496c	MSMEG_5897	mce4D	mce4 operon: lipid transfer	☑		✓			KstR1
Rv3497c	MSMEG_5898	mce4C	mce4 operon: lipid transfer	☑		✓		Essential	KstR1
Rv3498c	MSMEG_5899	mce4B	mce4 operon: lipid transfer	☑		✓			KstR1
Rv3499c	MSMEG_5900	mce4A	mce4 operon: lipid transfer	☑		✓		Essential	KstR1
Rv3500c	MSMEG_5901	supBh	mce4 operon: lipid transfer	☑		✓			KstR1
Rv3501c	MSMEG_5902	supAh	mce4 operon: lipid transfer	☑		✓		Essential	KstR1
Rv3502c	MSMEG_5903	hsd4A	steroid β-hydroxy-acyl-CoA dehydrogenase	□	✓	✓		Essential	KstR1
Rv3503c	MSMEG_5904	fdxD	ferredoxin	?	✓		Induced		KstR1
Rv3504	MSMEG_5906	fadE26	3-keto-4-cholene-24-oyl-CoA dehydrogenase α subunit	☑	✓			Essential	KstR1
Rv3505	MSMEG_5907	fadE27	3-keto-4-cholene-24-oyl-CoA dehydrogenase β subunit	☑	✓		Induced		KstR1
Rv3506	MSMEG_5908	fadD17	3-keto-chol-4-ene-24-oyl-CoA ligase	☑					KstR1
Rv3507	-	PE_PGRS53	PE family of glycine rich proteins	?
Rv3508	MSMEG_2146	PE_PGRS54	PE family of glycine rich proteins	?
Rv3509c	MSMEG_4348	ilvX	acetohydroxyacid synthase	?
Rv3510c	-	Rv3510c	conserved hypothetical protein	?
Rv3511	-	PE_PGRS55	PE family of glycine rich proteins	?
Rv3512	-	PE_PGRS56	PE family of glycine rich proteins	?
Rv3513c	-	fadD18	acyl-CoA ligase (fragment)	?
Rv3514	-	PE_PGRS57	PE family of glycine rich proteins	?
Rv3515c	MSMEG_5914	fadD19	3-keto-4-cholest-4-ene-26-oyl-CoA ligase	☑	✓	✓			KstR1
Rv3516	MSMEG_5915	echA19	enoyl-CoA hydratase	?	✓		Induced		KstR1
Rv3517	-		conserved hypothetical protein	?
Rv3518c	MSMEG_5918	cyp142	cholest-4-en-3-one 26-monooxygenase	☑	✓		Induced		KstR1
Rv3519	MSMEG_5919		conserved hypothetical protein	?				Essential	KstR1
Rv3520c	MSMEG_5920		coenzyme F420-dependent oxidoreductase	□	✓				KstR1
Rv3521	MSMEG_5921		conserved hypothetical protein	?	✓		Induced		KstR1
Rv3522	MSMEG_5922	ltp4	3-hydroxy-acyl-CoA aldolase	?	✓				KstR1
Rv3523	MSMEG_5923	ltp3	3-hydroxy-acyl-CoA aldolase	□	✓			Essential	KstR1
Rv3524	-		conserved membrane protein	?			Induced
Rv3525c	-		siderophore binding protein	?
Rv3526	MSMEG_5925	kshA	3-ketosteroid 9α-hydroxylase oxygenase component	☑	✓	✓			KstR1
Rv3527	MSMEG_5927		conserved hypothetical protein	?	✓				KstR1
Rv3528c	-		hypothetical protein	?
Rv3529c	MSMEG_5930		conserved hypothetical protein	?	✓				KstR1
Rv3530c	MSMEG_5931		oxidoreductase	?	✓				KstR1
Rv3531c	MSMEG_5932		conserved hypothetical protein	?	✓	✓			KstR1
Rv3532	-	PPE61	PPE family of glycine rich proteins	?
Rv3533c	-	PPE62	PPE family of glycine rich proteins	?
Rv3534c	MSMEG_5937	hsaF	4-hydroxy-2-oxohexanoate aldolase	□	✓	✓	Induced	Essential	KstR1
Rv3535c	MSMEG_5939	hsaG	propanal dehydrogenase	□	✓		Induced		KstR1
Rv3536c	MSMEG_5940	hsaE	2-hydroxyhexa-2,4-dienoate hydratase	□	✓	✓	Induced		KstR1
Rv3537	MSMEG_5941	kstD	3-keto-A4-steroid A1-dehydrogenase	☑	✓	✓	Induced, Essential		KstR1
Rv3538	MSMEG_5943	hsd4B	steroid 2-enoyl-CoA hydratase	□	✓		Induced		KstR1
Rv3539	-	PPE63	PE family of glycine rich proteins	?
Rv3540c	MSMEG_5990	ltp2	3-oxo-17-hydroxy-pregna-4-ene-22-oyl-CoA aldolase	□	✓	✓	Induced	Essential	KstR1
Rv3541c	MSMEG_5991		3-oxo-pregna-4,17-diene-22-oyl-CoA hydratase α subunit	□	✓	✓	Induced, Essential	Essential	KstR1
Rv3542c	MSMEG_5992		3-oxo-pregna-4,17-diene-22-oyl-CoA hydratase β subunit	□	✓	✓	Induced, Essential	Essential	KstR1
Rv3543c	MSMEG_5993	chsE1 (fadE28)	3-oxo-pregn-4-ene-22-oyl-CoA dehydrogenase β subunit	☑	✓	✓	Essential		KstR1
Rv3544c	MSMEG_5994	chsE2 (fadE29)	3-oxo-pregn-4-ene-22-oyl-CoA dehydrogenase α subunit	☑	✓	✓	Induced	Essential	KstR1
Rv3545c	MSMEG_5995	cyp125	cholest-4-en-3-one 26-monooxygenase	☑	✓	✓	Induced	Essential	KstR1
Rv3546	MSMEG_5996	fadA5	steroid β-keto-acyl-CoA thiolase	☑	✓	✓	Induced		KstR1
Rv3547	MSMEG_5998		conserved hypothetical protein	?					KstR1
Rv3548c	MSMEG_5999		short-chain-type dehydrogenase/reductase	?	✓				KstR2
Rv3549c	MSMEG_6000		short-chain-type dehydrogenase/reductase	?	✓				KstR2
Rv3550	MSMEG_6001		enoyl-CoA hydratase	?	✓				KstR2
Rv3551	MSMEG_6002		CoA-transferase α subunit	?	✓	✓	Essential	Essential	KstR2
Rv3552	MSMEG_6003		CoA-transferase β subunit	?	✓		Induced, Essential		KstR2
Rv3553	MSMEG_6004		oxidoreductase	?		✓	Induced, Essential		KstR2
Rv3554	-	fdxB	ferridoxin B	?			Induced	Induced
Rv3555c	MSMEG_5314		conserved hypothetical protein		✓		Induced	Induced
Rv3556c	MSMEG_6008	fadA6	thiolase	?	✓		Essential	Induced, Essential	KstR2
Rv3557	MSMEG_6009	kstR2	transcriptional repressor (TetR-like)	☑	✓		Induced		KstR2
Rv3558	-	PPE64	PPE family of glycine rich proteins	?
Rv3559c	MSMEG_6011		oxidoreductase	?	✓	✓			KstR2
Rv3560c	MSMEG_6012	fadE30	acyl-CoA dehydrogenase	□	✓	✓	Induced, Essential	Essential	KstR2
Rv3561	MSMEG_6013	fadD3	3aα-H-4α(3'-propanoate)-7aβ- methylhexahydro-1,5-indanedione-CoA synthase	☑	✓	✓	Induced		KstR2
Rv3562	MSMEG_6014	fadE31	steroid acyl-CoA dehydrogenase α subunit	□	✓		Induced		KstR2
Rv3563	MSMEG_6015	fadE32	steroid acyl-CoA dehydrogenase β subunit	□	✓	✓	Essential	Essential	KstR2
Rv3564	MSMEG_6016	fadE33	steroid acyl-CoA dehydrogenase β subunit	□	✓	✓	Induced		KstR2
Rv3565	MSMEG_6017	aspB	aspartate aminotransferase	?	✓				KstR2
Rv3566c	MSMEG_0306	nat	arylamine N-acetyltransferase	□	✓		Induced	Induced
Rv3567c	MSMEG_6035	hsaB	3-hydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17-dione 4-hydroxylase reductase component	☑	✓				KstR1
Rv3568c	MSMEG_6036	hsaC	3,4-dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione 4,5-dioxygenase	☑	✓	✓			KstR1
Rv3569c	MSMEG_6037	hsaD	4,5-9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolase	☑	✓	✓	Essential		KstR1
Rv3570c	MSMEG_6038	hsaA	3-hydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17-dione 4-monooxygenase component	☑	✓	✓	Essential		KstR1
Rv3571	MSMEG_6039	kshB	3-ketosteroid 9α-hydroxylase reductase component	☑	✓	✓	Induced		KstR1
Rv3572	MSMEG_6040		conserved hypothetical protein	?					KstR1
Rv3573c	MSMEG_6041	fadE34	cholest-4-en-3-one-26-oyl-CoA dehydrogenase	□	✓	✓			KstR1
Rv3574	MSMEG_6042	kstR1	transcriptional repressor (TetR-like)	☑	✓		Induced	Essential	KstR1

Mtb genes in the Cho region, KstR1, KstR2, and Mce3R regulons, and selected cholesterol-regulated genes or potential cholesterol metabolizing genes discussed in the text are included.

Genes in the Cho region are shaded with a gray background: (Van Der Geize et al., 2007;Nesbitt et al, 2010).

Transcriptionally up-regulated by cholesterol after 3 or 24 h: (Nesbitt et al, 2010).

Required for growth in cholesterol media: (Griffin et al, 2011).

Upregulated 24 h after THP-1 macrophage infection: (Fontán et al, 2007).

Induced in macrophages: (Schappinger et al, 2003).

Essential in macrophages using TraSH: (Rengaragan et al, 2005).

Essential in mice using TraSH: (Sassetti and Rubin, 2003).

ⁱ

Under control of the transcriptional repressors, KstR1: (Kendall et al., 2007); KstR2: (Kendall et al., 2010); Mce3R: (De La Paz Santangelo et al., 2009).