|Year : 2017 | Volume
| Issue : 1 | Page : 27-32
Spoligotype defined lineages of Mycobacterium tuberculosis and drug resistance: Merely a casual correlation?
Nikita Panwalkar1, Devendra S Chauhan2, Prabha Desikan1
1 Department of Microbiology and NRL, Bhopal Memorial Hospital and Research Centre, Bhopal, Madhya Pradesh, India
2 National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Indian Council of Medical Research, Agra, Uttar Pradesh, India
|Date of Web Publication||16-Mar-2017|
Department of Microbiology & NRL, Bhopal Memorial Hospital & Research Centre, Raisen Bypass Road, Karond, Bhopal, Madhya Pradesh
Source of Support: None, Conflict of Interest: None
Drug-resistant tuberculosis (TB) is a major challenge to TB control strategy worldwide. Analysis of genetic polymorphism among drug resistant Mycobacterium tuberculosis (MTB) strains may help provide some insight into the transmission dynamics of these strains. Spoligotyping is a widely used technique to identify genetic polymorphism, based on 43 known spacers interspersed between direct repeat regions. Considerable work has been done in various parts of the world using this technique to identify and analyse the polymorphic nature of MTB. Many studies have been carried out to determine the association of drug resistance with spoligotype defined lineages, and much data has been produced over the years. New information continues to be generated. This review aims to put together the findings of relevant studies in an attempt to understand the correlation of drug resistance with spoligotype defined lineages of MTB. This would help provide a perspective of the available data that can be used as a starting point to understand the molecular epidemiology of drug resistant TB.
Keywords: Correlation, drug resistance, Mycobacterium tuberculosis, spoligotype
|How to cite this article:|
Panwalkar N, Chauhan DS, Desikan P. Spoligotype defined lineages of Mycobacterium tuberculosis and drug resistance: Merely a casual correlation?. Indian J Med Microbiol 2017;35:27-32
|How to cite this URL:|
Panwalkar N, Chauhan DS, Desikan P. Spoligotype defined lineages of Mycobacterium tuberculosis and drug resistance: Merely a casual correlation?. Indian J Med Microbiol [serial online] 2017 [cited 2017 Sep 26];35:27-32. Available from: http://www.ijmm.org/text.asp?2017/35/1/27/202327
| ~ Introduction|| |
Drug-resistant tuberculosis (TB) presents a major challenge to TB control globally. An insight into the transmission dynamics of drug-resistant strains of TB would go a long way towards planning interventions for control of drug resistant TB. This has underlined the need to understand the correlation of drug resistance with genetic polymorphism among strains of Mycobacterium tuberculosis (MTB).
Considerable work has been done in various parts of the world towards describing the polymorphic nature of MTB.,, Several molecular techniques have been used in combination, or independently, in order to differentiate between the strains of MTB. Among these, a widely used technique is spoligotyping., It is used due to its robustness, reproducibility and ability to simultaneously detect and differentiate strains of MTB. Many studies have been carried out to determine the association of drug resistance with spoligotype defined lineages, and much data has been produced over the years. New information continues to be generated. This review aims to put together the findings of relevant studies in an attempt to understand the correlation of drug resistance with spoligotype defined lineages of MTB. This would help provide a perspective of the available data that can be used as a starting point to understand the molecular epidemiology of drug-resistant TB.
| ~ Spoligotype Defined Lineages and Drug Resistance|| |
The data generated by spoligotyping is based on the presence or absence of 43 known spacers, which is reduced to an octal code to compare with an international database called SITVITWEB which is an updated version of the SpolDB4 database. The SITVIT database incorporates a total of 7104 spoligotype patterns on 58,187 clinical isolates that are grouped into 2747 spoligotype international types (SITs) and 4357 orphan patterns. The term 'lineage' refers to a group of related genotypes that are defined by their spoligotype pattern.
Different lineages are represented differently in different geographic regions. This review discusses these lineages under the heads 'Beijing lineage' and 'non-Beijing lineages'. The Beijing lineage is prevalent in the East Asian and East European countries, but its global presence is noteworthy, particularly in the low incidence areas of the world indicating that human migration resulted in active cross-border dissemination of drug-resistant TB. A significant difference in the magnitude of drug resistance from different geographical regions has been documented.
The Beijing lineage is typically characterised by the absence of initial 34 spacer oligonucleotides and presence of spacers 35–43. This lineage was first identified in 1995 by Soolingen from the People's Republic of China. Since then, its ubiquitous presence has been reported from various parts of the world and studied extensively. However, there is a poor representation of Beijing strains in some parts of Latin America, South America, Central and North Europe.,,,
Association of Beijing lineage with drug resistance is well documented from different geographic areas including the Indian subcontinent and neighbouring countries.,,,, The drug-resistant classical SIT1 Beijing lineage is prominent in the Soviet countries and Saudi Arabia.,,, Drug resistance is thought to have developed independently among the different clones of Beijing strains., It has been proposed that the Beijing lineage has an increased ability to acquire drug resistance and disease transmissibility. It has also been suggested that infection with Beijing lineage strain is more common among younger people., Strains of the Beijing lineage have a higher capacity to proliferate within the human monocytes and the resistant Beijing strains display rapid growth compared to susceptible isolates. The emergence of multiple variants of Beijing lineage may be a reflection of genetic polymorphism leading to greater transmissibility and ability to acquire drug resistance.
Beijing lineage and multidrug-resistance
While the virulent nature of the Beijing lineage is well described, its association with drug-resistant relapse cases has also been documented. A study team from Bangladesh found that Beijing was the most prevalent lineage in that area, comprising 75% strains with multidrug resistance (MDR) in previously treated patients. Beijing strains associated with MDR have also been reported in the northern and central India., In Vietnam, MDR-TB was strongly associated with Beijing lineage, however, the association between genotype and resistance among treatment failures was not clear since the Beijing genotype was not an independent predictor of failure.
Studies from Estonia, China, Korea and Taiwan demonstrated significantly higher frequencies of MDR among the Beijing lineage., 27, ,, Colombia had 15.6% Beijing isolates, and most of them had MDR. Here, two subtypes of Beijing lineage were isolated-SIT1 and ST190. The latter was found to be associated with extensively drug-resistant TB (XDR-TB) and represented the largest cluster among isolates with MDR. A study conducted in Sweden identified 13% Beijing strains over a period of 15 years. The proportion of strains with MDR was significantly higher among Beijing strains than in non-Beijing strains. Turkey, with merely 6.3% prevalence of Beijing lineage, had 66.7% MDR in the lineage. The newly emerging virulent forms of Beijing lineage have been associated with high rates of MDR in South Africa.,, The Beijing strain was found to be linked with an outbreak of MDR-TB in the United States.,
However, a study from China reported that, though Beijing and Beijing-like strains were the most predominant circulating lineages, there was no significant association with MDR. A report from Finland documented 19 MDR cases over a period of 12 years, of which only 7 (36.8%) were of Beijing lineage. Although there was no association of MDR with the Beijing lineage in Peru.
Beijing lineage and other drug-resistance patterns
Beijing lineage and resistance to rifampicin
Beijing strains resistant to only rifampicin (RIF) have also been observed. Association of Beijing lineage with only RIF resistance have been reported from China  with most common mutations at codon 531, 526 and 511. RIF-resistant Beijing isolates were also found to be clustered, suggestive of active transmission of those resistant strains in that region. A study from Russia has reported genetic homogeneity among classical ST1 Beijing isolates conferring mutations associated with RIF resistance.
Beijing lineage and resistance to isoniazid
Studies from China demonstrated an active transmission of isoniazid (INH) resistant Beijing lineage strains with frequent mutation at katG 315, and comparatively less frequent mutation at-15 inh, locus., Similar findings were reported from the West Bank, Palestinian territories. Association between Beijing lineage and mutations in the katG gene was also documented in a study from Sweden. The authors of this study found that a majority of the Beijing strains with INH resistance had katG 315 substitution, whereas some of the Beijing strains had-15 inhA mutations.
Beijing lineage and resistance to streptomycin, ethambutol, pyrazinamide
An association of Beijing lineage and mutations conferring resistance to streptomycin (STR) was demonstrated in a study from Poland. A study carried out at Barcelona, Spain, reported 4.47% Beijing strains with mutations in the rpsL gene at codons 88 and 43. A study from China had documented significant association of ethambutol resistance with Beijing genotype. A strong association of pyrazinamide (PZA) resistance with MDR among strains of Beijing lineage was reported in a study from Iran.
Beijing lineage and resistance to linezolid, moxifloxacin
The Beijing lineage was found to be significantly associated with linezolid resistance in MDR and XDR-TB in China. No association was found between moxifloxacin resistance and Beijing genotype in China.
Various non-Beijing lineages have been reported from different geographical regions of the world. The Central Asian (CAS) and East-African Indian (EAI) lineage are prevalent in Tanzania, India and in the Indian subcontinent.,,, Haarlem (H), LAM, and T lineages are frequently isolated in Africa, Central America, Europe and South America.,, These lineages have been documented to be associated with varying degrees of drug resistance.,, In many high incidence countries, EAI lineage has been reported to be associated with reduced transmissibility and drug resistance when evaluated with other lineages whilst drug-resistant mutant strains have also been reported from CAS lineage.,,,,,
Non-Beijing lineages and multidrug-resistance
A study group from Saudi Arabia reported over-representation of EAI lineage among strains with MDR. A report from Mumbai, India showed that a significant number of strains of CAS, T1, EAI5 and EAI3 lineages were associated with XDR-TB. Association of CAS lineage with XDR TB has also been reported from Pakistan. From the same region, a high prevalence of H lineage has been identified among MDR stains. An association of PZA resistance with MDR strains of the H lineage was documented in a study from Iran. A study from Iraq reported CAS as a major lineage associated with MDR amongst previously treated patients. CAS could be correlated significantly with MDR in Sudan. MDR was found to be associated with LAM_CAM sub-lineage in Nigeria. A study from Brazil found an association of MDR with a highly dominant RD Rio sub-lineage of LAM lineage. Association of MDR with RD Rio sub-lineage was reported in another study among Latin American and Spanish population. A study from Poland found that the LAM lineage was associated with MDR., A study from southern Brazil identified LAM and T as the predominant lineages, both associated with RIF and INH resistance.
Non-Beijing lineages and other resistance patterns
A study from Myanmar reported preponderance of EAI lineage in that region associated with monoresistance to anti-TB drugs. RIF and STR mono-resistance were identified from India among strains of the CAS and T lineage. A study team from Iran found that PZA mono-resistance was more frequent among strains of CAS and EAI lineage. A study team from Poland analysed INH monoresistant phenotypes and identified T, H, U and S as the most prevalent lineages associated with INH monoresistance. INH-resistant MTB isolates harbouring mutations at codon S315G, associated with LAM lineage, were reported from West Bank, Palestinian Territories. An association of monoresistance to STR, INH and RIF was observed with LAM and H lineages in French Departments of Americas. A Mexican study group observed non-MDR, RIF or INH resistance in LAM9 and T1 lineages but not in H3 lineages.
The LAM lineage was found to be prevalent among HIV-positive patients in Mexico. However, the investigators could not correlate the drug resistance to spoligotype pattern. A study group from Peru did not find any association between drug resistance and specific spoligotypes among HIV-negative TB patients. However, MDR, but not INH or RIF mono-resistance, was found to be associated with SIT42/LAM9 and SIT53/T1 strains among HIV-associated TB patients. The authors of this study, therefore, did not support the hypothesis of strain-specific propensity for the acquisition of resistance among the genetically diversified MTB strains in that region. In Italy, T, H, LAM, S and X, lineages were found to be highly prevalent but none of them had significant drug resistance. In South-Western Uganda, there is a prevalence of Uganda lineage though no significant association with drug resistance was detected. A study from Karachi, Pakistan, revealed that no specific lineage was associated with fluoroquinolone resistance.
To summarise, genetic polymorphism exists within all lineage of MTB. The spoligotype defined lineages are represented differently in different geographical areas of the world. High rates of drug resistance may not be necessarily associated with the prevalent lineages in that region. Different lineages have shown association with some patterns of drug resistance. Beijing lineage has been consistently reported to have a significantly higher drug resistance compared to other lineages, though in certain parts of the world, this is not the case. The spoligotype lineages other than Beijing were found to be comparatively less associated with drug resistance. However, it is still uncertain whether correlation with drug resistance is merely casual or whether there is a firm link between the two.
This review was inspired by a project on genetic polymorphism of MTB strains that was funded by the Indian Council of Medical Research, India.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| ~ References|| |
Perizzolo PF, Dalla Costa ER, Ribeiro AW, Spies FS, Ribeiro MO, Dias CF, et al.
Characteristics of multidrug-resistant Mycobacterium tuberculosis in Southern Brazil. Tuberculosis (Edinb) 2012;92:56-9.
Kisa O, Tarhan G, Gunal S, Albay A, Durmaz R, Saribas Z, et al.
Distribution of spoligotyping defined genotypic lineages among drug-resistant Mycobacterium tuberculosis
complex clinical isolates in Ankara, Turkey. PLoS One 2012;7:e30331.
Augustynowicz-Kopec E, Jagielski T, Zwolska Z. Genetic diversity of isoniazid-resistant Mycobacterium tuberculosis
isolates collected in Poland and assessed by spoligotyping. J Clin Microbiol 2008;46:4041-4.
Tessema B, Beer J, Merker M, Emmrich F, Sack U, Rodloff AC, et al.
Molecular epidemiology and transmission dynamics of Mycobacterium tuberculosis
in Northwest Ethiopia: New phylogenetic lineages found in Northwest Ethiopia. BMC Infect Dis 2013;13:131.
Cardoso Oelemann M, Gomes HM, Willery E, Possuelo L, Batista Lima KV, Allix-Béguec C, et al.
The forest behind the tree: Phylogenetic exploration of a dominant Mycobacterium tuberculosis
strain lineage from a high tuberculosis burden country. PLoS One 2011;6:e18256.
Demay C, Liens B, Burguière T, Hill V, Couvin D, Millet J, et al.
SITVITWEB – A publicly available international multimarker database for studying Mycobacterium tuberculosis genetic diversity and molecular epidemiology. Infect Genet Evol 2012;12:755-66.
Mokrousov I, Vyazovaya A, Otten T, Zhuravlev V, Pavlova E, Tarashkevich L, et al. Mycobacterium tuberculosis
population in Northwestern Russia: An update from Russian-EU/Latvian border region. PLoS One 2012;7:e41318.
van Soolingen D, Qian L, de Haas PE, Douglas JT, Traore H, Portaels F, et al.
Predominance of a single genotype of Mycobacterium tuberculosis
in countries of east Asia. J Clin Microbiol 1995;33:3234-8.
Glynn JR, Whiteley J, Bifani PJ, Kremer K, van Soolingen D. Worldwide occurrence of Beijing/W strains of Mycobacterium tuberculosis
: A systematic review. Emerg Infect Dis 2002;8:843-9.
Abadía E, Sequera M, Ortega D, Méndez MV, Escalona A, Da Mata O, et al. Mycobacterium tuberculosis
ecology in Venezuela: Epidemiologic correlates of common spoligotypes and a large clonal cluster defined by MIRU-VNTR-24. BMC Infect Dis 2009;9:122.
Ritacco V, López B, Cafrune PI, Ferrazoli L, Suffys PN, Candia N, et al. Mycobacterium tuberculosis
strains of the Beijing genotype are rarely observed in tuberculosis patients in South America. Mem Inst Oswaldo Cruz 2008;103:489-92.
Fenner L, Gagneux S, Helbling P, Battegay M, Rieder HL, Pfyffer GE, et al. Mycobacterium tuberculosis
transmission in a country with low tuberculosis incidence: Role of immigration and HIV infection. J Clin Microbiol 2012;50:388-95.
Ghebremichael S, Groenheit R, Pennhag A, Koivula T, Andersson E, Bruchfeld J, et al.
Drug resistant Mycobacterium tuberculosis
of the Beijing genotype does not spread in Sweden. PLoS One 2010;5:e10893.
Vadwai V, Shetty A, Supply P, Rodrigues C. Evaluation of 24-locus MIRU-VNTR in extrapulmonary specimens: Study from a tertiary centre in Mumbai. Tuberculosis (Edinb) 2012;92:264-72.
Sankar MM, Singh J, Diana SC, Singh S. Molecular characterization of Mycobacterium tuberculosis
isolates from North Indian patients with extrapulmonary tuberculosis. Tuberculosis (Edinb) 2013;93:75-83.
Purwar S, Chaudhari S, Katoch VM, Sampath A, Sharma P, Upadhyay P, et al.
Determination of drug susceptibility patterns and genotypes of Mycobacterium tuberculosis
isolates from Kanpur district, North India. Infect Genet Evol 2011;11:469-75.
Chatterjee A, D'Souza D, Vira T, Bamne A, Ambe GT, Nicol MP, et al.
Strains of Mycobacterium tuberculosis
from Western Maharashtra, India, exhibit a high degree of diversity and strain-specific associations with drug resistance, cavitary disease, and treatment failure. J Clin Microbiol 2010;48:3593-9.
Banu S, Gordon SV, Palmer S, Islam MR, Ahmed S, Alam KM, et al.
Genotypic analysis of Mycobacterium tuberculosis
in Bangladesh and prevalence of the Beijing strain. J Clin Microbiol 2004;42:674-82.
Sinkov VV, Savilov ED, Ogarkov OB. Reconstruction of the epidemic history of the Beijing genotype of Mycobacterium tuberculosis
in Russia and former soviet countries using spoligotyping. Mol Genet Microbiol Virol 2011;26:120-5.
Afanas'ev MV, Ikryannikova LN, Il'ina EN, Kuz'min AV, Larionova EE, Smirnova TG, et al.
Molecular typing of Mycobacterium tuberculosis
circulated in Moscow, Russian Federation. Eur J Clin Microbiol Infect Dis 2011;30:181-91.
Baranov AA, Mariandyshev AO, Mannsåker T, Dahle UR, Bjune GA. Molecular epidemiology and drug resistance of widespread genotypes of Mycobacterium tuberculosis
in Northwestern Russia. Int J Tuberc Lung Dis 2009;13:1288-93.
Varghese B, Supply P, Allix-Béguec C, Shoukri M, Al-Omari R, Herbawi M, et al.
Admixed phylogenetic distribution of drug resistant Mycobacterium tuberculosis
in Saudi Arabia. PLoS One 2013;8:e55598.
Krüüner A, Hoffner SE, Sillastu H, Danilovits M, Levina K, Svenson SB, et al.
Spread of drug-resistant pulmonary tuberculosis in Estonia. J Clin Microbiol 2001;39:3339-45.
Sandegren L, Groenheit R, Koivula T, Ghebremichael S, Advani A, Castro E, et al.
Genomic stability over 9 years of an isoniazid resistant Mycobacterium tuberculosis
outbreak strain in Sweden. PLoS One 2011;6:e16647.
Hu Y, Ma X, Graviss EA, Wang W, Jiang W, Xu B. A major subgroup of Beijing family Mycobacterium tuberculosis
is associated with multidrug resistance and increased transmissibility. Epidemiol Infect 2011;139:130-8.
Borgdorff MW, de Haas P, Kremer K, van Soolingen D. Mycobacterium tuberculosis
Beijing genotype, the Netherlands. Emerg Infect Dis 2003;9:1310-3.
Buu TN, Huyen MN, Lan NT, Quy HT, Hen NV, Zignol M, et al.
The Beijing genotype is associated with young age and multidrug-resistant tuberculosis in rural Vietnam. Int J Tuberc Lung Dis 2009;13:900-6.
Li Q, Whalen CC, Albert JM, Larkin R, Zukowski L, Cave MD, et al.
Differences in rate and variability of intracellular growth of a panel of Mycobacterium tuberculosis
clinical isolates within a human monocyte model. Infect Immun 2002;70:6489-93.
Iwamoto T, Fujiyama R, Yoshida S, Wada T, Shirai C, Kawakami Y. Population structure dynamics of Mycobacterium tuberculosis
Beijing strains during past decades in Japan. J Clin Microbiol 2009;47:3340-3.
Huyen MN, Buu TN, Tiemersma E, Lan NT, Dung NH, Kremer K, et al.
Tuberculosis relapse in Vietnam is significantly associated with Mycobacterium tuberculosis
Beijing genotype infections. J Infect Dis 2013;207:1516-24.
Banu S, Mahmud AM, Rahman MT, Hossain A, Uddin MK, Ahmed T, et al.
Multidrug-resistant tuberculosis in admitted patients at a tertiary referral hospital of Bangladesh. PLoS One 2012;7:e40545.
Desikan P, Chauhan DS, Sharma P, Panwalkar N, Yadav P, Ohri BS. Clonal diversity and drug resistance in Mycobacterium tuberculosis
isolated from extra-pulmonary samples in central India – A pilot study. Indian J Med Microbiol 2014;32:434-7.
] [Full text]
Buu TN, Huyen MN, van Soolingen D, Lan NT, Quy HT, Tiemersma EW, et al.
The Mycobacterium tuberculosis
Beijing genotype does not affect tuberculosis treatment failure in Vietnam. Clin Infect Dis 2010;51:879-86.
Shamputa IC, Lee J, Allix-Béguec C, Cho EJ, Lee JI, Rajan V, et al.
Genetic diversity of Mycobacterium tuberculosis
isolates from a tertiary care tuberculosis hospital in South Korea. J Clin Microbiol 2010;48:387-94.
Choi GE, Jang MH, Song EJ, Jeong SH, Kim JS, Lee WG, et al.
IS6110-restriction fragment length polymorphism and spoligotyping analysis of Mycobacterium tuberculosis
clinical isolates for investigating epidemiologic distribution in Korea. J Korean Med Sci 2010;25:1716-21.
Chiu YC, Huang SF, Yu KW, Lee YC, Feng JY, Su WJ. Characteristics of pncA mutations in multidrug-resistant tuberculosis in Taiwan. BMC Infect Dis 2011;11:240.
Ferro BE, Nieto LM, Rozo JC, Forero L, van Soolingen D. Multidrug-resistant Mycobacterium tuberculosis
, Southwestern Colombia. Emerg Infect Dis 2011;17:1259-62.
Evans J, Stead MC, Nicol MP, Segal H. Rapid genotypic assays to identify drug-resistant Mycobacterium tuberculosis
in South Africa. J Antimicrob Chemother 2009;63:11-6.
Cowley D, Govender D, February B, Wolfe M, Steyn L, Evans J, et al.
Recent and rapid emergence of W-Beijing strains of Mycobacterium tuberculosis
in Cape Town, South Africa. Clin Infect Dis 2008;47:1252-9.
Hesseling AC, Marais BJ, Kirchner HL, Mandalakas AM, Brittle W, Victor TC, et al.
Mycobacterial genotype is associated with disease phenotype in children. Int J Tuberc Lung Dis 2010;14:1252-8.
Moss AR, Alland D, Telzak E, Hewlett D Jr., Sharp V, Chiliade P, et al.
A city-wide outbreak of a multiple-drug-resistant strain of Mycobacterium tuberculosis
in New York. Int J Tuberc Lung Dis 1997;1:115-21.
Yuan L, Huang Y, Mi LG, Li YX, Liu PZ, Zhang J, et al.
There is no correlation between sublineages and drug resistance of Mycobacterium tuberculosis
Beijing/W lineage clinical isolates in Xinjiang, China. Epidemiol Infect 2015;143:141-9.
Vasankari T, Soini H, Liippo K, Ruutu P. MDR-TB in Finland – Still rare despite the situation in our neighbouring countries. Clin Respir J 2012;6:35-9.
Taype CA, Agapito JC, Accinelli RA, Espinoza JR, Godreuil S, Goodman SJ, et al.
Genetic diversity, population structure and drug resistance of Mycobacterium tuberculosis
in Peru. Infect Genet Evol 2012;12:577-85.
Guo YL, Liu Y, Wang SM, Li CY, Jiang GL, Shi GL, et al.
Genotyping and drug resistance patterns of Mycobacterium tuberculosis
strains in five provinces of China. Int J Tuberc Lung Dis 2011;15:789-94.
Tang K, Sun H, Zhao Y, Guo J, Zhang C, Feng Q, et al.
Characterization of rifampin-resistant isolates of Mycobacterium tuberculosis
from Sichuan in China. Tuberculosis (Edinb) 2013;93:89-95.
Hu Y, Mathema B, Jiang W, Kreiswirth B, Wang W, Xu B. Transmission pattern of drug-resistant tuberculosis and its implication for tuberculosis control in eastern rural China. PLoS One 2011;6:e19548.
Mäkinen J, Marjamäki M, Haanperä-Heikkinen M, Marttila H, Endourova LB, Presnova SE, et al.
Extremely high prevalence of multidrug resistant tuberculosis in Murmansk, Russia: A population-based study. Eur J Clin Microbiol Infect Dis 2011;30:1119-26.
Zhou A, Nawaz M, Duan Y, Moore JE, Millar BC, Xu J, et al.
Molecular characterization of isoniazid-resistant Mycobacterium tuberculosis
isolates from Xi'an, China. Microb Drug Resist 2011;17:275-81.
Hu Y, Hoffner S, Jiang W, Wang W, Xu B. Extensive transmission of isoniazid resistant M. tuberculosis
and its association with increased multidrug-resistant TB in two rural counties of eastern China: A molecular epidemiological study. BMC Infect Dis 2010;10:43.
Ereqat S, Nasereddin A, Azmi K, Abdeen Z, Greenblatt CL, Spigelman M, et al.
Genetic characterization of Mycobacterium tuberculosis
in the West Bank, Palestinian Territories. BMC Res Notes 2012;5:270.
Jagielski T, Ignatowska H, Bakula Z, Dziewit L, Napiórkowska A, Augustynowicz-Kopec E, et al.
Screening for streptomycin resistance-conferring mutations in Mycobacterium tuberculosis
clinical isolates from Poland. PLoS One 2014;9:e100078.
Tudó G, Rey E, Borrell S, Alcaide F, Codina G, Coll P, et al.
Characterization of mutations in streptomycin-resistant Mycobacterium tuberculosis
clinical isolates in the area of Barcelona. J Antimicrob Chemother 2010;65:2341-6.
Zhang D, An J, Wang J, Hu C, Wang Z, Zhang R, et al.
Molecular typing and drug susceptibility of Mycobacterium tuberculosis
isolates from Chongqing Municipality, China. Infect Genet Evol 2013;13:310-6.
Doustdar F, Khosravi AD, Farnia P. Mycobacterium tuberculosis
genotypic diversity in pyrazinamide-resistant isolates of Iran. Microb Drug Resist 2009;15:251-6.
Zhang Z, Pang Y, Wang Y, Liu C, Zhao Y. Beijing genotype of Mycobacterium tuberculosis
is significantly associated with linezolid resistance in multidrug-resistant and extensively drug-resistant tuberculosis in China. Int J Antimicrob Agents 2014;43:231-5.
El Sahly HM, Teeter LD, Jost KC Jr., Dunbar D, Lew J, Graviss EA. Incidence of moxifloxacin resistance in clinical Mycobacterium tuberculosis
isolates in Houston, Texas. J Clin Microbiol 2011;49:2942-5.
Eldholm V, Matee M, Mfinanga SG, Heun M, Dahle UR. A first insight into the genetic diversity of Mycobacterium tuberculosis
in Dar es Salaam, Tanzania, assessed by spoligotyping. BMC Microbiol 2006;6:76.
Sharma P, Chauhan DS, Upadhyay P, Faujdar J, Lavania M, Sachan S, et al.
Molecular typing of Mycobacterium tuberculosis
isolates from a rural area of Kanpur by spoligotyping and mycobacterial interspersed repetitive units (MIRUs) typing. Infect Genet Evol 2008;8:621-6.
Desikan P, Chauhan DS, Sharma P, Panwalkar N, Gautam S, Katoch VM. A pilot study to determine genetic polymorphism in Mycobacterium tuberculosis
isolates in Central India. Indian J Med Microbiol 2012;30:470-3.
] [Full text]
Bazira J, Matte M, Asiimwe BB, Joloba LM. Genetic diversity of Mycobacterium tuberculosis
in Mbarara, South Western Uganda. Afr Health Sci 2010;10:306-11.
Roetzer A, Schuback S, Diel R, Gasau F, Ubben T, di Nauta A, et al.
Evaluation of Mycobacterium tuberculosis
typing methods in a 4-year study in Schleswig-Holstein, Northern Germany. J Clin Microbiol 2011;49:4173-8.
Brudey K, Driscoll JR, Rigouts L, Prodinger WM, Gori A, Al-Hajoj SA, et al. Mycobacterium tuberculosis
complex genetic diversity: Mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology. BMC Microbiol 2006;6:23.
Ahmed N, Ehtesham NZ, Hasnain SE. Ancestral Mycobacterium tuberculosis
genotypes in India: Implications for TB control programmes. Infect Genet Evol 2009;9:142-6.
Ahmed N, Hasnain SE. Molecular epidemiology of tuberculosis in India: Moving forward with a systems biology approach. Tuberculosis (Edinb) 2011;91:407-13.
Dalla Costa ER, Ribeiro MO, Silva MS, Arnold LS, Rostirolla DC, Cafrune PI, et al.
Correlations of mutations in katG, oxyR-ahpC and inhA genes and in vitro
susceptibility in Mycobacterium tuberculosis
clinical strains segregated by spoligotype families from tuberculosis prevalent countries in South America. BMC Microbiol 2009;9:39.
Ali A, Hasan Z, Moatter T, Tanveer M, Hasan R. M. tuberculosis
Central Asian Strain 1 MDR isolates have more mutations in rpoB and katG genes compared with other genotypes. Scand J Infect Dis 2009;41:37-44.
Jagielski T, Augustynowicz-Kopec E, Zozio T, Rastogi N, Zwolska Z. Spoligotype-based comparative population structure analysis of multidrug-resistant and isoniazid-monoresistant Mycobacterium tuberculosis
complex clinical isolates in Poland. J Clin Microbiol 2010;48:3899-909.
Dalla Costa ER, Lazzarini LC, Perizzolo PF, Díaz CA, Spies FS, Costa LL, et al. Mycobacterium tuberculosis
of the RDRio genotype is the predominant cause of tuberculosis and associated with multidrug resistance in Porto Alegre City, South Brazil. J Clin Microbiol 2013;51:1071-7.
Ritacco V, Iglesias MJ, Ferrazoli L, Monteserin J, Dalla Costa ER, Cebollada A, et al.
Conspicuous multidrug-resistant Mycobacterium tuberculosis
cluster strains do not trespass country borders in Latin America and Spain. Infect Genet Evol 2012;12:711-7.
Ahmed N, Dobrindt U, Hacker J, Hasnain SE. Genomic fluidity and pathogenic bacteria: Applications in diagnostics, epidemiology and intervention. Nat Rev Microbiol 2008;6:387-94.
Ajbani K, Rodrigues C, Shenai S, Mehta A. Mutation detection and accurate diagnosis of extensively drug-resistant tuberculosis: Report from a tertiary care center in India. J Clin Microbiol 2011;49:1588-90.
Hasan R, Jabeen K, Ali A, Rafiq Y, Laiq R, Malik B, et al.
Extensively drug-resistant tuberculosis, Pakistan. Emerg Infect Dis 2010;16:1473-5.
Ayaz A, Hasan Z, Jafri S, Inayat R, Mangi R, Channa AA, et al
. Characterizing Mycobacterium tuberculosis
isolates from Karachi, Pakistan: Drug resistance and genotypes. Int J Infect Dis 2012;16:e303-9.
Merza MA, Farnia P, Salih AM, Masjedi MR, Velayati AA. First insight into the drug resistance pattern of Mycobacterium tuberculosis
in Dohuk, Iraq: Using spoligotyping and MIRU-VNTR to characterize multidrug resistant strains. J Infect Public Health 2011;4:41-7.
Sharaf Eldin GS, Fadl-Elmula I, Ali MS, Ali AB, Salih AL, Mallard K, et al.
Tuberculosis in Sudan: A study of Mycobacterium tuberculosis
strain genotype and susceptibility to anti-tuberculosis drugs. BMC Infect Dis 2011;11:219.
Thumamo BP, Asuquo AE, Abia-Bassey LN, Lawson L, Hill V, Zozio T, et al.
Molecular epidemiology and genetic diversity of Mycobacterium tuberculosis
complex in the Cross River State, Nigeria. Infect Genet Evol 2012;12:671-7.
Jagielski T, Augustynowicz-Kopec E, Zozio T, Rastogi N, Zwolska Z. Spoligotype-based comparative population structure analysis of multidrug-resistant and INH-monoresistant Mycobacterium tuberculosis
complex clinical isolates in Poland. J Clin Microbiol 2010;48:3899-909.
Phyu S, Stavrum R, Lwin T, Svendsen ØS, Ti T, Grewal HM. Predominance of Mycobacterium tuberculosis
EAI and Beijing lineages in Yangon, Myanmar. J Clin Microbiol 2009;47:335-44.
Shanmugam S, Selvakumar N, Narayanan S. Drug resistance among different genotypes of Mycobacterium tuberculosis
isolated from patients from Tiruvallur, South India. Infect Genet Evol 2011;11:980-6.
Millet J, Streit E, Berchel M, Bomer AG, Schuster F, Paasch D, et al.
A systematic follow-up of Mycobacterium tuberculosis
drug-resistance and associated genotypic lineages in the French departments of the Americas over a seventeen-year period. Biomed Res Int 2014;2014:689852.
Bocanegra-García V, Garza-González E, Cruz-Pulido WL, Guevara-Molina YL, Cantú-Ramírez R, González GM, et al.
Molecular assessment, drug-resistant profile, and spacer oligonucleotide typing (spoligotyping) of Mycobacterium tuberculosis
strains from Tamaulipas, México. J Clin Lab Anal 2014;28:97-103.
Lopez-Alvarez R, Badillo-Lopez C, Cerna-Cortes JF, Castillo-Ramirez I, Rivera-Gutierrez S, Helguera-Repetto AC, et al.
First insights into the genetic diversity of Mycobacterium tuberculosis
isolates from HIV-infected Mexican patients and mutations causing multidrug resistance. BMC Microbiol 2010;10:82.
Sheen P, Couvin D, Grandjean L, Zimic M, Dominguez M, Luna G, et al.
Genetic diversity of Mycobacterium tuberculosis
in Peru and exploration of phylogenetic associations with drug resistance. PLoS One 2013;8:e65873.
Garzelli C, Lari N, Cuccu B, Tortoli E, Rindi L. Impact of immigration on tuberculosis in a low-incidence area of Italy: A molecular epidemiological approach. Clin Microbiol Infect 2010;16:1691-7.
Bazira J, Asiimwe BB, Joloba ML, Bwanga F, Matee MI. Mycobacterium tuberculosis
spoligotypes and drug susceptibility pattern of isolates from tuberculosis patients in South-Western Uganda. BMC Infect Dis 2011;11:81.
Rafiq Y, Jabeen K, Hasan R, Jafri S, Laiq R, Malik F, et al.
Fluoroquinolone resistance among Mycobacterium tuberculosis
strains from Karachi, Pakistan: Data from community-based field clinics. Antimicrob Agents Chemother 2011;55:929-30.