Novel katG mutations causing isoniazid resistance in clinical M. tuberculosis isolates

Figures & data

Table 1 Isolate stratification based on substitutions in katG and inhA promoter

Observed mutations	Number of INH^R isolates	Number of INH^S isolates
katG S315T (AGC-ACC)	191	1
katG S315T (AGC-ACC) + inhA -15C-T	28	0
inhA -15C-T	24	1
katG S315T (AGC-ACC) + inhA -8 (T-C or T-A)^a	39	0
inhA -17G-T	1	0
katG S315T (AGC-ACC) + inhA -17G-T	8	0
katG S315T (AGC-ACC) + inhA -34 (C-G or C-T)^a	2	0
Other previously characterized resistance conferring katG mutations and canonical mutation(s)	4	0
Standalone other previously characterized resistance conferring katG mutations	3	0
Standalone novel katG	15	0
Novel katG and canonical mutations	9	0
No mutations (other than R463) in katG or inhA promoter	8	32
Total	332	34
katGR463L (CGG-CTG) (marker for genetic group 3)	191	22

Note: In this article, we define canonical mutations as those occurring in codon 315 of katG or in positions -17, -15, or -8 of inhA promoter region.

^aThese mutations always appeared in combination with S315T.

Figure 1 Distribution of novel and known katG SNPs.

Table 2 Novel katG substitutions in isolates lacking canonical mutations

Amino acid substitution(s) discovered in the katG	MIC µg/mL	Phenotypic grouping^a	NO of INH^R isolates
Y64S (TAT-TCT)^b	3	INH^R other DST unknown	1
Y95C (TAC-TGC)^b	0.5	INH^R other DST unknown	1^c
P131T (CCG-ACG)^d, ^b	0.5	INH^R other DST unknown	1^c, ^e
A139P (GCC-CCC)^f	>10	INH^R other DST unknown	1^c
D142G (GAC-GGC)^d, ^b	>10	INH^R other DST unknown	1^c
A162V (GCG-GTG)^d, ^b	3	INH^R other DST unknown	1^c
G269D (GGT-GAT)^d, ^b	>10	INH^R other DST unknown	1^c
T306P (ACC-CCC)^d, ^b	Not done	MDR^+	1^c, ^e
R385W (CGG-TGG)^g	>10	INH^R other DST unknown	1^c
D387G (GAT-GGT)^d, ^g	≤10	INH^R other DST unknown	2^c
T394M (ACG-ATG)^d, ^f	Not done	XDR	1
Q439P (CAG-CCG)^b	Not done	MDR	1
F483L (TTC-CTC)^b	3	INH^R other DST unknown	1^c
A541D (GCC-GAC)^d, ^b	>10	INH^R other DST unknown	1

Table 3 Novel katG mutations in isolates that also harbor the canonical mutations

Novel substitutions	Canonical mutation(s)	Phenotypic grouping^a	NO of INH^R isolates
G32D (GGC-GAC)	inhA:-15C-T	Other Pre-XDR	1^b
V47E (GTA-GAA)	inhA:-15C-T	XDR	1^b
D194G (GAT-GGT)	katG: S315T (AGC-ACC)	MDR^+	1^b
A256T (GCC-ACC)	inhA:-15C-T	MDR^+	1
N596S (AAC-AGC) and Y597H (TAC-CAC)	inhA:-15C-T	XDR	1^b
T667P (ACC-CCC)	inhA:-15C-T	XDR	2^b
M624V (ATG-GTG)	katG: S315T (AGC-ACC)	XDR	1^b
M624V (ATG-GTG)	katG: S315T (AGC-ACC) and inhA:-8 T-A	XDR	1^b