Table 4 Drug-resistance mutations and corresponding phenotypic drug resistance detected.

From: High rate of drug resistance among tuberculous meningitis cases in Shaanxi province, China

Individual drug

Phenotypic resistance (Strain No.)

Resistance-associated mutations

MIC a (Critical concentration b ) μg/ml

Genes

Nucleotide change*

Amino acid change

Isoniazid (4)

H,R,S (#11)

kat G

315,AGC→ACC

S→T

>32.0 (4.0)

463,CGG→CTG

R→L c

H,R,E (#18)

315,AGC→ACC

S→T

>32.0 (4.0)

463,CGG→CTG

R→L

H,R,C,A,K (#19)

315,AGC→ACC

S→T

>32.0 (4.0)

463,CGG→CTG

R→L

H (#27)

315,AGC→ACC

S→T

>32.0 (4.0)

463,CGG→CTG

R→L

inhA or promotor

Rifampin (4)

H,R,S (#11)

rpoB

430,CTG→CCG e

L→P

2.0 (1.0)

H,R,E (#18)

450,TCG→TTG e

S→L

>8.0 (1.0)

H,R,C,A,K (#19)

452,CTG→CCG e

L→P

8.0 (1.0)

R (#15) d

2.0 (1.0)

Ethambutol (2)

H,R,E (#18)

embB

306,ATG→ATA

M→I

20.0 (5.0)

E (#2) d

>20.0 (5.0)

Quinolones (0)

H,R,E (#18)

gyrA

95,AGC→ACC f

S→T

Mfx-0.3 (2.0)

90,GCG→GTG

A→V

Lfx-0.6 (2.0)

gyrB

Injectables (6)

H,R,S (#11)

rpsL

43,AAG→AGG

K→R

S > 4.0 (2.0)

gidB

92,GAA→GAC c

E→D

K-4.0 (5.0)

205,GCA→GCG c

A→A

A-2.0 (4.0)

 

C-2.5 (5.0)

S (#14)

rpsL

43,AAG→AGG

K→R

S > 4.0 (2.0)

gidB

92,GAA→GAC

E→D

K-4.0 (5.0)

205,GCA→GCG

A→A

A-2.0 (4.0)

 

C-5.0 (5.0)

S (#1)

gidB

92,GAA→GAC

E→D

S > 4.0 (2.0)

205,GCA→GCG

A→A

K-8.0 (5.0)

A-4.0 (4.0)

C-5.0 (5.0)

K (#9)

gidB

16,CTT→CGT

L→R

S-2.0 (2.0)

K-16.0 (5.0)

A-8.0 (4.0)

C-5.0 (5.0)

H,R,S,C,A,K (#19)

gidB

92,GAA→GAC

E→D

S > 4.0 (2.0)

205,GCA→GCG

A→A

K > 128.0 (5.0)

rrs-KAN

1401, A→G

A > 32.0 (4.0)

C-20.0 (5.0)

C,A,K (#26)

S-4.0 (2.0)

K-32.0(5.0)

A-8.0 (4.0)

C-20.0 (5.0)

−(#16)

rpsL

39, ACC→ACT

T→T

S-2.0 (2.0)

gidB

92,GAA→GAC

E→D

K-8.0(5.0)

205,GCA→GCG

A→A

A-1.0 (4.0)

C-5.0 (5.0)

H (#27)

rpsL

43, AAG→AGG

K→R

S-2.0 (2.0)

gidB

92,GAA→GAC

E→D

K-4.0(5.0)

205,GCA→GCG

A→A

A-2.0 (4.0)

C-5.0 (5.0)

eis

  1. MIC-Minimum Inhibitory Concentration; H- isoniazid; R- rifampin; E- ethambutol; Mfx-moxifloxacin; Lfx-levofloxacin; S-streptomycin; K- kanamycin, A-amikacin; C-capreomycin; RRDR-Rifampin Resistance Determining Region.
  2. aMIC-Mean Inhibitory Concentration.
  3. bCritical concentration as recommended by WHO and CLSI23.
  4. cDetected in all 20 Beijing and 1 atypical Beijing strain.
  5. dResistance identified by L-J solid DST and MGIT 960 MIC.
  6. eL511P, S531L, L533P with Escherichia coli numbering (all within the 81 base pair RRDR).
  7. fDetected in all the isolates, both drug resistant and drug susceptible; *compared to H37Rv.