rpoB Mutations are Associated with Variable Levels of Rifampin and Rifabutin Resistance in Mycobacterium tuberculosis

Figures & data

Table 1 Distribution of rpoB Mutations and MICs of RIF and RFB

rpoB Mutations^a		MIC (µg/mL)		No. of Mutated Isolates
M. tuberculosis	E. coli	RIF	RFB
P45S/S450L	P25S/S531L	≥128	≥16	1
V170F	V146F	16	≥16	1
V170F/H445N	V146F/H526N	16	8	1
T400I/H445Y	T481I/H526Y	≥128	≥16	1
Q429H/H445Y	Q510H/H526Y	≥128	≥16	1
L430P	L511P	4	1	1
L430P/S431G	L511P/S512G	16	2	1
L430R/D435G	L511R/D516G	8	0.5	1
L430P/D435G	L511P/D516G	32	1	1
L430P/H445N	L511P/H526N	≥128	≥16	1
Q432H/F433-D435del*	Q513H/F514-D516del*	8	0.12	1
Q432K	Q513K	≥128	≥16	2
Q432L	Q513L	≥128	≥16	2
Q432P	Q513P	≥128	1	1
D435E/S441L	D516E/S522L	≥128	0.5	1
D435G/L452P	D516G/L533P	≥128	≥16	1
D435G/L452P	D516G/L533P	64	1	1
D435G/I491N	D516G/I572N	8	0.5	1
D435V	D516V	4	0.25	1
D435V	D516V	4	1	1
D435V	D516V	16	0.25	1
D435V	D516V	16	1	1
D435V	D516V	64	0.25	1
D435V	D516V	64	0.5	1
D435V	D516V	64	1	1
D435V	D516V	≥128	0.5	1
D435V	D516V	≥128	2	1
D435V/S450L	D516V/S531L	64	8	1
D435Y	D516Y	0.5	≤0.12	1
D435Y	D516Y	1	0.25	1
D435Y/S450G	D516Y/S531G	16	4	1
D435del*/E460G	D516del*/E541G	≥128	4	1
S441L	S522L	16	0.5	1
H445D	H526D	≥128	2	1
H445D	H526D	≥128	4	4
H445D	H526D	≥128	8	3
H445D	H526D	≥128	≥16	3
H445L	H526L	2	0. 5	1
H445L	H526L	4	0.25	1
H445N/L452P	H526N/L533P	≥128	4	1
H445N/L452P	H526N/L533P	≥128	8	1
H445P/K446Q	H526P/K527Q	≥128	≥16	1
H445Q/I491M	H526Q/I572M	8	0.25	1
H445R	H526R	≥128	0.5	1
H445R	H526R	≥128	1	1
H445R	H526R	≥128	≥16	2
H445Y	H526Y	2.0	0.25	1
H445Y	H526Y	16	1	1
H445Y	H526Y	≥128	4	1
H445Y	H526Y	≥128	8	2
H445Y	H526Y	≥128	≥16	3
S450L	S531L	32	4	1
S450L	S531L	64	8	1
S450L	S531L	64	≥16	2
S450L	S531L	≥128	1	1
S450L	S531L	≥128	2	6
S450L	S531L	≥128	4	9
S450L	S531L	≥128	8	8
S450L	S531L	≥128	≥16	20
S450F	S531F	≥128	8	1
S450L/I488V	S531L/I569V	≥128	4	1
S450L/I491V	S531L/I572V	≥128	4	1
S450L/G759S	S531L/G846S	≥128	8	1
S450L/Q1056K	S531L/Q1264K	≥128	≥16	1
L452P	L533P	2	0.5	1
L452P	L533P	2	1	1
L452P	L533P	1	0.25	1

Notes: ^aMutations are showed using either the M. tuberculosis or E. coli numbering system. *Mutation reported for the first time; del, deletion.

Table 2 Logistic Regression Multivariate Model Results Between rpoB Mutations and Drug Resistance

Mutation	Isolates	RIF			RFB
		Median MIC (IQR)	OR	P	Median MIC (IQR)	OR	P
Q432K	2	128 (128, 128)	7.31	0.127	16 (16, 16)	13.75	0.047*
Q432L	2	128 (128, 128)	7.31	0.127	16 (16, 16)	13.75	0.047*
H445N	4	128 (72, 128)	/	/	8 (6, 12)	1.60	0.748
H445R	4	128 (128, 128)	15.89	<0.01**	8.5 (0.75, 16)	17.98	0.028*
H445L	2	3 (2, 4)	7.31	0.127	0.375 (0.25, 0.5)	2.77	1.000
H445D	11	128 (128, 128)	45.99	<0.000**	8 (4, 16)	86.16	<0.000**
H445Y	9	128 (128, 128)	37.39	<0.000**	16 (8, 16)	70.06	<0.000**
L430P	4	24 (10, 80)	7.31	0.127	1.5 (1, 9)	15.99	0.020*
L452P	7	2 (2, 128)	11.59	0.034*	1 (0.5, 8)	5.73	0.205
D435G	5	32 (8, 64)	7.31	0.127	1 (0.5, 1)	2.26	0.911
D435V	10	64 (16, 64)	37.39	<0.000**	0.75 (0.25, 1)	4.99	0.083
D435Y	3	1 (0.5 16)	6.31	0.312	0.25 (0.12, 4)	3.14	0.751
V170F	2	16 (16, 16)	3.06	0.492	12 (8, 16)	5.79	0.295
S441L	2	72 (16, 128)	7.31	0.127	0.5 (0.5, 0.5)	2.77	1.000
S450L	54	128 (128, 128)	226.69	<0.000**	8 (4, 16)	425.87	<0.000**

Note: *P< 0.05 (significant); **P <0.01 (highly significant).

Table 3 Logistic Regression Multivariate Model Results Between rpoB Mutations and High-Level MIC

Drug and Mutation	OR Value	P
High-level RIF MIC
H445R	26.09 (4.24, Infinity)	0.002**
H445D	75.53 (14.68, Infinity)	<0.000**
H445Y	40.80 (4.84, >999.99)	<0.000**
L452P	3.98 (0.52, 26.68)	0.205
D435V	0.77 (0.05, 5.95)	1.000
S450L	50.39 (16.39, 192.83)	<0.000**
High-level RFB MIC
Q432K	20.46 (2.37, Infinity)	0.024*
Q432L	20.46 (2.37, Infinity)	0.024*
H445R	9.24 (0.60, 143.99)	0.120
H445D	11.12 (2.28, 56.64)	0.002**
H445Y	31.43 (4.95, 359.98)	<0.000**
L430P	3.17 (0.06, 45.44)	0.700
S450L	17.35 (6.68, 50.38)	<0.000**

Note: *P< 0.05 (significant); **P <0.01 (highly significant).