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European Journal of Medical Research logoLink to European Journal of Medical Research
. 2020 Apr 21;25:14. doi: 10.1186/s40001-020-00412-7

Correction to: Molecular characterization of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates identifies local transmission of infection in Kuwait, a country with a low incidence of TB and MDR-TB

Noura M Al-Mutairi 1, Suhail Ahmad 1,, Eiman M Mokaddas 1
PMCID: PMC7171810  PMID: 32312322

Correction to: Eur J Med Res (2019) 24:38 10.1186/s40001-019-0397-2

The original publication of this article [1] contained few erroneous paragraphs and errors in Table 1 and Table 2. The first four paragraphs are in the ‘Results’ section while the last four paragraphs are in the ‘Discussion’ section. The errors in Table 1 involve the number of isolates tested for pyrazinamide and pyrazinamide susceptible isolates, ethambutol-susceptible isolates with a mutation and number of resistant isolates with a mutation for streptomycin. The error in Table 2 involves wrong codon number for a mutation in isolate KM17-01 in Cluster XII for gidB gene. The updated informations have been indicated in bold and also refer corrected Tables 1 and 2.

Table 1.

Phenotypic resistance by MGIT 960 system to anti-TB drugs among 93 multidrug-resistant M. tuberculosis isolates and number of susceptible and resistant isolates with mutations in target genes for each drug

Anti-tuberculosis drug No. of isolates tested No. of susceptible isolates No. of susceptible isolates with mutationa No. of resistant isolates No. (%) of resistant isolates with mutationa
Rifampicin 93 0 0 93 93 (100)
Isoniazid 93 0 0 93 92 (98.9)
Pyrazinamide 46 10 0 36 30 (83.3)
Ethambutol 93 52 39b 41 38 (92.7)
Streptomycin 93 34 0 59 51 (86.4)

aResistance conferring mutations were detected in rpoB for rifampicin, katG + inhA for isoniazid, pncA for pyrazinamide, embB for ethambutol, and rpsL + rrs for streptomycin

bM. tuberculosis isolates with embB mutations usually confer low level of resistance to ethambutol which are often missed by the MGIT 960 system [23, 28]

Table 2.

Detailed clinical, demographic and molecular characteristics of 42 M. tuberculosis isolates in 16 (Cluster I to Cluster XVI) clusters

Cluster no. Clinica specimen Isolate no. Year of isolation Patient’s nationality Spoligotyping data Genetic alteration detected in
SIT Mtb family rpoB katG inhA pncA embB rpsL rrs gidB rpsA
I Sputum KM06-153 2006 Indian 255 Beijing TCG456TTG ACG315ACC WT WT ATG306GTG AAG43AGG WT N. D. N. D.
CSF KM09-22 2009 Indian 255 Beijing TCG456TTG ACG315ACC WT WT ATG306GTG AAG43AGG WT N. D. N. D.
Sputum KM13-37 2013 Indian 1 Beijing TCG456TTG ACG315ACC WT WT ATG306GTG AAG43AGG WT N. D. N. D.
FNA KM16-06 2016 Nepalese 1 Beijing TCG456TTG ACG315ACC WT WT ATG306GTG AAG43AGG WT N. D. N. D.
FNA KM17-03 2017 Indian 1 Beijing TCG456TTG ACG315ACC WT WT ATG306GTG AAG43AGG WT N. D. N. D.
II Sputum KM14-58 2014 Nepalese 1 Beijing TCG456TTG ACG315ACC WT GTG139GCG ATG306GTG AAG43AGG WT GAA92GAC + GCA205GCG CGA212CGC
Sputum KM14-69 2014 Indian 1 Beijing TCG456TTG ACG315ACC WT GTG139GCG ATG306GTG AAG43AGG WT GCA205GCG WT
III Sputum KM08-501 2008 Kuwaiti 1 Beijing TCG456TTG ACG315ACC WT GGT139GTT ATG306GTG AAG43AGG WT GAA92GAC + GCA205GCG CGA212CGC
Sputum KM08-502 2008 Kuwaiti 1 Beijing TCG456TTG ACG315ACC WT GGT139GTT ATG306GTG AAG43AGG WT GAA92GAC + GCA205GCG CGA212CGC
Sputum KM09-207 2009 Indian 1 Beijing TCG456TTG ACG315ACC WT GGT139GTT ATG306GTG AAG43AGG WT GAA92GAC + GCA205GCG CGA212CGC
IV Sputum KM12-05 2012 Ethiopian 21 CAS1-Kili TCG456TTG ACG315ACC WT Ins193A (FS) + TCC65TCT ATG306GTG AAG88AGG WT N. D. N. D.
Sputum KM12-17 2012 Ethiopian 1144 T1 TCG456TTG ACG315ACC WT Ins193A (FS) + TCC65TCT ATG306GTG AAG88AGG WT N. D. N. D.
Sputum KM15-08 2015 Ethiopian 21 CAS1-Kili TCG456TTG ACG315ACC WT Ins193A (FS) + TCC65TCT ATG306GTG AAG88AGG WT N. D. N. D.
V Sputum KM07-333 2007 Indonesian Orphan N. A. TCG456TTG ACG315ACC WT WT WT WT WT N. D. N. D.
Sputum KM10-23 2010 Indian 355 EAI3-IND TCG456TTG ACG315ACC WT WT WT WT WT N. D. N. D.
VI Sputum KM07-293 2007 Filipino 194 LAM2 TCG456TTG ACG315ACC WT WT CAG497CGG WT WT N. D. N. D.
Sputum KM12-01 2012 Filipino 25 CAS1-Delhi TCG456TTG ACG315ACC WT WT CAG497CGG WT WT N. D. N. D.
VII Sputum KM09-202 2009 Ethiopian 47 H1 GTC176TTC ACG315ACC WT WT WT WT WT N. D. N. D.
Sputum KM15-17 2015 Indian 47 H1 GTC176TTC ACG315ACC WT WT WT WT WT N. D. N. D.
VIII Sputum KM14-67 2014 Ethiopian 149 T3-ETH TCG456TTG ACG315ACC WT − 11 A/G ATG306ATC WT WT GGT69GAT WT
Sputum KM15-21 2015 Ethiopian 149 T3-ETH TCG456TTG ACG315ACC WT − 11 A/G ATG306ATC WT WT GGT69GAT WT
IX Sputum KM07-283 2007 Indian 26 CAS1-Delhi TCG456TTG ACG315ACC WT TCC65TCT ATG306ATA WT WT N. D. N. D.
Sputum KM14-68 2014 Indian Orphan N. A. TCG456TTG ACG315ACC WT TCC65TCT ATG306ATA WT WT N. D. N. D.
Sputum KM17-20 2017 Kuwaiti 1 Beijing TCG456TTG ACG315ACC WT − 11 A/G CAG497CGG AAG43AGG WT GAA92GAC + GCA205GCG WT
X Sputum KM17-22 2017 Kuwaiti 1 Beijing TCG456TTG ACG315ACC WT − 11 A/G CAG497CGG AAG43AGG WT GAA92GAC + GCA205GCG CGA212CGC
Sputum KM17-73 2017 Indian 1 Beijing TCG456TTG ACG315ACC WT − 11 A/G CAG497CGG AAG43AGG WT GAA92GAC + GCA205GCG CGA212CGC
Pus KM11-503 2011 Kuwaiti 1 Beijing TCG456TTG ACG315ACC WT − 11 A/G GGC406GAC AAG43AGG WT GAA92GAC + GCA205GCG CGA212CGC
Sputum KM14-56 2014 Kuwaiti 1 Beijing TCG456TTG ACG315ACC WT − 11 A/G GGC406GAC AAG43AGG WT GAA92GAC + GCA205GCG CGA212CGC
XI Sputum KM15-13 2015 Kuwaiti 1 Beijing TCG456TTG ACG315ACC WT − 11 A/G GGC406GAC AAG43AGG WT GAA92GAC + GCA205GCG CGA212CGC
Sputum KM15-26 2015 Kuwaiti 1 Beijing TCG456TTG ACG315ACC WT − 11 A/G GGC406GAC AAG43AGG WT GAA92GAC + GCA205GCG CGA212CGC
Sputum KM17-02 2015 Kuwaiti 1 Beijing TCG456TTG ACG315ACC WT − 11 A/G GGC406GAC AAG43AGG WT GAA92GAC + GCA205GCG CGA212CGC
Sputum KM17-69 2017 Kuwaiti 1 Beijing TCG456TTG ACG315ACC WT − 11 A/G GGC406GAC AAG43AGG WT GAA92GAC + GCA205GCG CGA212CGC
XII Sputum KM16-32 2016 Egyptian 19 EAI2-Manila CAC451TAC ACG315ACC − 15 C/T GAA37AAA CTG355CTA + GAG378GCG WT WT GTG110GTT + GCA205GCG WT
Sputum KM17-01 2017 Filipino 19 EAI2-Manila CAC451TAC ACG315ACC − 15 C/T GAA37AAA CTG355CTA + GAG378GCG WT WT CTC59TTC + GTG110GTT + GCA205GCG WT
XIII Pus KM07-297 2007 Indian Orphan N. A. CAC451GAC WT − 15 C/T TCC65TCG + Ins 453T (FS) ATG306CTG WT WT N. D. N. D.
FNA KM11-502 2015 Indian 3361 T1 CAC451GAC WT − 15 C/T TCC65TCG + Ins 453T (FS) ATG306CTG WT WT N. D. N. D.
XIV Sputum KM06-48 2006 Egyptian 53 T1 TCG456TTG WT − 15 C/T WT WT WT WT N. D. N. D.
Tissue KM06-277 2006 Filipino 19 EAI2-Manila TCG456TTG WT − 15 C/T WT WT WT WT N. D. N. D.
XV Sputum KM16-33 2016 Indian 8 EAI3/EAI5 CAC451TAC ACG315ACC WT CTG35CCG ATG306GTG + GAG378GCG AAG43AGG WT GTG110GTT + GCA205GCG WT
Sputum KM17-06 2017 Filipino 8 EAI3/EAI5 CAC451TAC ACG315ACC WT CTG35CCG ATG306GTG + GAG378GCG AAG43AGG WT GTG110GTT + GCA205GCG WT
XVI Sputum KM07-231 2007 Indian Orphana CAS1-Delhi ATG440ATA + GAC441TAC ACG315ACC WT TCC65TCT GGC406TGC WT WT GCA205GCG + Del 350G (FS) WT
Sputum KM07-252 2007 Syrian Orphana CAS1-Delhi ATG440ATA + GAC441TAC ACG315ACC WT TCC65TCT GGC406TGC WT WT GCA205GCG + Del 350G (FS) WT

Clusters containing MDR-TB strains with identical patterns and isolated within a period of nearly 2 years are shown as underlined. Synonymous mutations are italicized

N. A., not applicable; N. D., not done; CSF, cerebrospinal fluid; FNA, fine needle aspirate; SIT, shared international type; Mtb family, M. tuberculosis family; WT, wild-type sequence; Ins, insertion mutation; (FS), frame shift mutation, fine needle aspirate

aBoth isolates displayed identical spoligotyping pattern

Incorrect: Although all 93 MDR-TB isolates were tested for susceptibility to pyrazinamide, only 47 isolates yielded interpretable results; 11 isolates were susceptible and 36 were resistant to this drug including 15 isolates that were resistant to all five drugs. The remaining 46 MDR-TB strains failed to grow at the reduced pH in the absence of the drug.

Correct: Although all 93 MDR-TB isolates were tested for susceptibility to pyrazinamide, only 46 isolates yielded interpretable results; 10 isolates were susceptible and 36 were resistant to this drug including 15 isolates that were resistant to all five drugs. The remaining 47 MDR-TB strains failed to grow at the reduced pH in the absence of the drug.

Incorrect: The proportion of MDR-TB isolates exhibiting resistance conferring mutations in target genes varied for different anti-TB drugs, being highest for rifampicin and lowest for streptomycin (Table 1).

Correct: The proportion of MDR-TB isolates exhibiting resistance conferring mutations in target genes varied for different anti-TB drugs, being highest for rifampicin and lowest for streptomycin among SIRE drugs (Table 1).

Incorrect: PCR-sequencing of pncA identified mutations in 30 of 36 MDR-TB strains phenotypically resistant to pyrazinamide and 23 of 46 isolates for which phenotypic DST data for pyrazinamide was not available while all 11 isolates phenotypically susceptible to pyrazinamide contained wild-type sequence for pncA.

Correct: PCR-sequencing of pncA identified mutations in 30 of 36 MDR-TB strains phenotypically resistant to pyrazinamide and 23 of 47 isolates for which phenotypic DST data for pyrazinamide was not available while all 10 isolates phenotypically susceptible to pyrazinamide contained wild-type sequence for pncA.

Incorrect: Fifty isolates contained mutations at embB306 (M306V, n = 28; M306I, n = 19 and M306L, n = 3), 15 isolates contained a mutated embB406 (G406D, n = 8; G406A, n = 4; G406C, n = 2 and G406S, n = 1), 10 isolates contained a mutated embB497 (Q497R, n = 6; Q497K, n = 3 and Q497H, n = 1) and one isolate contained a mutation (Y319S) at embB319.

Correct: Fifty isolates contained mutations at embB306 (M306V, n = 28; M306I, n = 19 and M306L, n = 3), 16 isolates contained a mutated embB406 (G406D, n = 8; G406A, n = 5; G406C, n = 2 and G406S, n = 1), 10 isolates contained a mutated embB497 (Q497R, n = 6; Q497K, n = 3 and Q497H, n = 1) and one isolate contained a mutation (Y319S) at embB319.

Incorrect: Forty-nine of 59 MDR-TB strains additionally resistant to streptomycin contained a mutation in the target genes analysed (Table 1), many of which have been described previously [23, 28]. These included 44 isolates with a mutation in rpsL (K43R, n = 33; K43T, n = 1; K88R, n = 5; K88T, n = 4; K88M, n = 1), four isolates with a mutation in rrs 500 or 900 region (A514C, n = 1; C517T, n = 1; G878A, n = 1 and A906G, n = 1) and one isolate with rpsL K88R + rrs C602A double mutation.

Correct: Fifty-one of 59 MDR-TB strains additionally resistant to streptomycin contained a mutation in the target genes analysed (Table 1), many of which have been described previously [23, 28]. These included 44 isolates with a mutation in rpsL (K43R, n = 33; K43T, n = 1; K88R, n = 5; K88T, n = 4; K88M, n = 1), four isolates with a mutation in rrs 500 or 900 region (A514C, n = 1; C517T, n = 1; G878A, n = 1 and A906G, n = 1) and three isolates with double mutation inrpsLandrrsgenes (rpsLK43R + rrsC527T, n = 1;rpsLK88T + rrsC517T, n = 1;rpsLK88R + rrsC602A, n = 1).

Incorrect: Resistance conferring mutations in rpsL and/or rrs gene were detected in majority (49 of 59, 83%) of streptomycin-resistant but not in any streptomycin-susceptible MDR-TB strain while mutations in embB gene were detected in both ethambutol-resistant and -susceptible MDR-TB strains, as described in our previous studies [23, 28].

Correct: Resistance conferring mutations in rpsL and/or rrs gene were detected in majority (51 of 59, 86.4%) of streptomycin-resistant but not in any streptomycin-susceptible MDR-TB strain while mutations in embB gene were detected in both ethambutol-resistant and -susceptible MDR-TB strains, as described in our previous studies [23, 28].

Incorrect: Phenotypic DST results for pyrazinamide were available for only 47 of 93 MDR-TB strains while the remaining 46 isolates failed to grow at lower pH. No pncA mutation was detected in 50 pansusceptible strains. Analysis of 93 MDR-TB strains showed that 30 of 36 MDR-TB strains phenotypically resistant to pyrazinamide and 23 of 46 isolates for which DST data for pyrazinamide was not available contained a mutation in pncA while all 11 MDR-TB strains phenotypically susceptible to pyrazinamide contained wild-type sequence for pncA.

Correct: Phenotypic DST results for pyrazinamide were available for only 46 of 93 MDR-TB strains while the remaining 47 isolates failed to grow at lower pH. No pncA mutation was detected in 50 pansusceptible strains. Analysis of 93 MDR-TB strains showed that 30 of 36 MDR-TB strains phenotypically resistant to pyrazinamide and 23 of 47 isolates for which DST data for pyrazinamide was not available contained a mutation in pncA while all 10 MDR-TB strains phenotypically susceptible to pyrazinamide contained wild-type sequence for pncA.

Incorrect: The two isolates in Cluster XII were also very closely related, with the second isolate (KM17-01) displaying an additional mutation (L95F) in gidB which is considered as a hot-spot for mutations in the M. tuberculosis genome [21, 57].

Correct: The two isolates in Cluster XII were also very closely related, with the second isolate (KM17-01) (Table 2) displaying an additional mutation (L59F) in gidB which is considered as a hot-spot for mutations in the M. tuberculosis genome [21, 57].

Footnotes

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Contributor Information

Noura M. Al-Mutairi, Email: noura.j@hsc.edu.kw

Suhail Ahmad, Email: suhail_ah@hsc.edu.kw.

Eiman M. Mokaddas, Email: e.mokaddas@hsc.edu.kw

Reference

  • 1.Al-Mutairi NM, Ahmad S, Mokaddas EM. Molecular characterization of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates identifies local transmission of infection in Kuwait, a country with a low incidence of TB and MDR-TB. Eur J Med Res. 2019;24:38. doi: 10.1186/s40001-019-0397-2. [DOI] [PMC free article] [PubMed] [Google Scholar]

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