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Table 1 Non-synonymous single nucleotide polymorphisms (SNPs) in genes associated with bedaquiline and clofazimine resistance in clinical MTB isolates (n = 48)

From: Variants associated with Bedaquiline (BDQ) resistance identified in Rv0678 and efflux pump genes in Mycobacterium tuberculosis isolates from BDQ naïve TB patients in Pakistan

Resistance phenotype

  

MIC (µg/ml)

Variants in resistance associated genes

Study ID

of isolates

Lineage

BDQ

CFZ

atpE

(1,461,045–1,461,290)

Rv0678

(778,990–779,487)

pepQ

(2,859,300–2,860,418)

Rv1979c

(2,221,719–2,223,164)

mmpS5

(778,477–778,905)

mmpL5

(775,586–778,480)

XDR (BDQ-R)

S9

L3

0.5

1

-

R107Cβ

-

-

-

I948V + T794I

XDR (BDQ-R)

S1

L3

0.5

0.5

-

-

-

-

-

I948V + T794I

S2

A18A

-

-

-

-

I948V + T794I

S3

-

RAMAELQDLADVGLRALGDAPPQRSRRLREMRDLLAYMENVVSDALGRYSQRTGEDD109RGNGRTAGPGfs α

-

-

-

I948V + T794I

S4

-

SGGISTNARMLIQFGFIERLAVAGDRRTYFRLRPNAFAAGERERIRAMAELQDLADVGLRALGDAPPQRSRRLREMRDLLAYMENVVSDALGRYSQRTGEDD64SGGSAPMPGCfsα

-

-

-

I948V + T794I

S5

-

L40Fβ

-

-

-

I948V + T794I

S10

 

G25VCRVfsα

-

-

-

I948V + T794I

S6£

0.25

 

R50Qβ

-

-

-

I948V + T794I

S7

0.25

-

-

-

-

-

I948V + T794I

S8

0.12

-

-

-

-

-

I948V + T794I

pre-XDR

(BDQ-I)

S23

L3

0.25

1

-

-

 

F144*

 

I948V + T794I

S16

L3

0.25

0.5

-

S63Rε

-

-

-

I948V + T794I

S18,

-

-

-

-

-

I948V + T794I

S19

S17

0.25

-

-

-

-

-

I948V + T794I

S20

-

S63Gε

-

-

-

I948V + T794I

S22

0.12

-

-

-

-

-

I948V + T794I

pre-XDR

(BDQ-S)

S31

L2

0.12

0.5

-

-

-

-

-

I948V + T794I

S32

L3

-

-

-

-

-

I948V + T794I

S35

S38

S40

S34

-

-

-

-

-

I948V + T794I

SS15

0.12

-

-

-

-

-

I948V + T794I

SS14

0.03

-

-

-

-

-

I948V + T794I

S39

0.06

0.5

-

-

-

-

-

I948V + T794I

SS18

0.06

-

-

-

-

-

I948V + T794I

S36

0.03

0.06

-

-

-

-

-

I948V + T794I

SS16

0.12

-

-

-

-

-

I948V + T794I

SS19

 ≤ 0.008

 ≤ 0.015

-

-

-

-

-

I948V + T794I

MDR (BDQ-I)

S21

L3

0.25

1

-

-

-

-

-

I948V + T794I

MDR (BDQ-S)

SS16

L3

0.003

0.12

-

-

-

-

-

I948V + T794I

SS11

L4

0.06

0.06

-

-

-

-

-

I948V

SS18

SS17

L3

-

-

-

-

-

I948V + T794I

SS20

L3

 ≤ 0.008

 ≤ 0.015

-

-

-

-

-

I948V + T794I

SS12

L3

0.015

 ≤ 0.01

5

-

-

-

-

-

I948V + T794I

SS13

0.06

Pan drug susceptible

SS1

L3

0.03

0.12

-

-

-

-

-

I948V + T794I

SS4

L2

0.03

-

-

-

-

-

I948V + T794I + D767N

SS5

L4

-

-

-

-

-

I948V + T794I + A61A

SS9

L3

0.06

-

-

-

-

-

I948V + T794I

SS10

SS6

L3

-

-

-

-

-

I948V + T794I

SS7

SS2

L3

0.06

0.12

-

-

-

-

-

I948V + T794I

SS3

L3

0.06

-

-

R7Q

-

-

I948V + T794I + L221L

SS8

L1

-

-

-

-

-

I948V + T794I

  1. BDQ bedaquiline (MIC R ≥ 0.5 µg/ml, I = 0.25 µg/ml), CFZ clofazimine (> 0.5 µg/ml), MDR multidrug resistant, XDR extensively drug resistant, drug susceptible Mycobacterium tuberculosis (MTB) isolates as per susceptibility testing using broth microdilution method against first and second line antimycobacterials. MTB isolates were categorized into drug resistant types based on updated definitions shared by the WHO (25)
  2. α = previously unreported frameshift mutations, β = previously unreported missense mutations, ε = previously reported missense mutation at amino acid position
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BMC Microbiology

ISSN: 1471-2180

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