[Diffusion-weighted imaging characteristics of uterine leiomyomas with different pathological subtypes at 3.0 T].

OBJECTIVE: To investigate the imaging features of uterine leiomyomas with different pathological subtypes on DWI. METHODS: Clinical records and MR images of pathologically confirmed uterine leiomyomas were retrospectively collected from the Second Affiliated Hospital of Wenzhou Medical University from June 2012 to April 2015. A total of 60 uterine leiomyomas were found and evaluated.All the patients were divided into three groups according to different pathological types, which included 17 cases of cellular leiomyomas, 10 cases of degenerated leiomyomas and 33 cases of ordinary leiomyomas.The DWI signal and ADC values in cellular portion of the lesions and adjacent normal myometrium (the control group) were measured. RESULTS: (1) Most cellular leiomyomas showed hyperintensity on DWI (15/17), while degenerated leiomyomas manifested hypointensity, isointensity or hyperintensity signal on DWI, and most ordinary leiomyomas displayed isointensity signal on DWI (57.6%, 19/33). (2) The ADC values of cellular leiomyomas, degenerated leiomyomas and ordinary leiomyomas were (1.01±0.14)×10(-3) mm(2)/s, (1.73±0.49)×10(-3) mm(2)/s and (1.38±0.22)×10(-3) mm(2)/s respectively.The ADC values of adjacent normal myometrium (the control group) were (1.35±0.16)×10(-3) mm(2)/s.There were no significant statistical differences in the ADC values between ordinary leiomyomas and adjacent normal myometrium (P=0.623). There were significant statistical differences in the ADC values among other groups(all P<0.05). (3)The ROC curve showed that the diagnostic threshold for cellular leiomyomas was 1.11×10(-3) mm(2)/s, the sensitivity and specificity were 88.2%and 93.0% respectively. CONCLUSION: The signal intensity on DWI and the ADC values are different in uterine leiomyomas with different pathological subtypes.Combination of these two parameters in clinical practice may be helpful to reflect the histopathological characteristics of uterine leiomyomas.

Identification and genetic mapping of the putative Thinopyrum intermedium-derived dominant powdery mildew resistance gene PmL962 on wheat chromosome arm 2BS.

KEY MESSAGE: Powdery resistance putatively derived from Thinopyrum intermedium in the wheat line L962 is controlled by a single dominant gene designated PmL962 and mapped to chromosome arm 2BS. Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a destructive disease affecting the production of wheat (Triticum aestivum). Powdery mildew resistance was putatively transferred from Thinopyrum intermedium to the common wheat line L962, which conferred resistance to multiple Chinese Bgt isolates. Genetic analysis of the powdery mildew response was conducted by crossing the resistant line L962 with the susceptible line L983. Disease assessments of the F1, F2, and F2:3 populations from the cross L983/L962 indicated that resistance was controlled by a single dominant gene. A total of 373 F2:3 lines and 781 pairs of genomic simple sequence repeat (SSR) primers were employed to determine the chromosomal location of the resistance gene. The gene was linked to four publicly available and recently developed wheat genomic SSR markers and seven EST-STS markers. The resistance gene was mapped to chromosome arm 2BS based on the locations of the linked markers. Pedigree, molecular marker and resistance response data indicated that the powdery mildew resistance gene in L962 is novel. It was temporarily designated PmL962. It is flanked by Xwmc314 and BE443737at genetic distances of 2.09 and 3.74 cM, respectively, and located in a 20.77 cM interval that is co-linear with a 269.4 kb genomic region on chromosome 5 in Brachypodium distachyon and a 223.5 kb genomic region on rice (Oryza sativa) chromosome 4. The markers that are closely linked to this gene have potential applications in marker-assisted breeding.

A novel quantitative trait locus for Fusarium head blight resistance in chromosome 7A of wheat.

A Chinese Spring-Sumai 3 chromosome 7A disomic substitution line (CS-Sumai 3-7ADSL) was reported to have a high level of Fusarium head blight (FHB) resistance for symptom spread within a spike (Type II) and low deoxynivalenol accumulation in infected kernels (Type III), but a quantitative trait locus (QTL) on chromosome 7A has never been identified from this source. To characterize QTL on chromosome 7A, we developed 191 7A chromosome recombinant inbred lines (7ACRIL) from a cross between Chinese Spring and CS-Sumai 3-7ADSL and evaluated both types of resistance in three greenhouse experiments. Two major QTL with Sumai 3 origin, conditioning both Type II and III resistance, were mapped in the short arm of chromosomes 3B (3BS) and near the centromere of chromosome 7A (7AC). The 3BS QTL corresponds to previously reported Fhb1 from Sumai 3, whereas 7AC QTL, designated as Fhb7AC, is a novel QTL identified from CS-Sumai 3-7ADSL in this study. Fhb7AC explains 22% phenotypic variation for Type II and 24% for Type III resistance. Marker Xwmc17 is the closest marker to Fhb7AC for both types of resistance. Fhb1 and Fhb7AC were additive, and together explained 56% variation for Type II and 41% for Type III resistance and resulted in 66% reduction in FHB severity and 84% reduction in deoxynivalenol (DON) content. Haplotype analysis of Sumai 3 parents revealed that Fhb7AC originated from Funo, an Italian cultivar. Fhb7AC has the potential to be used in improving wheat cultivars for both types of resistance.

[Single-strand conformational polymorphism markers associated with a major QTL for fusarium head blight resistance in wheat].

A major quantitative trait locus (QTL) associated with resistance to Fusarium head blight (FHB) was identified on chromosome 3BS between simple sequence repeat (SSR) markers Xgwm389 and Xgwm493 in wheat 'Ning 7840', a derivative from 'Sumai 3'. However, the marker density of SSR in the QTL region was much lower than that required for marker-assisted selection (MAS) and map-based cloning. The objective of this study was to exploit new markers to increase marker density in this QTL region by using single-strand conformational polymorphism (SSCP) markers developed from wheat expressed sequence tags (ESTs) on 3BS bin 8-0.78-1.0. Sixty-nine out of 85 SSCP primer pairs amplified PCR (polymerase chain reaction) products from the genomic DNA of 'Chinese Spring'. Thirty-four primer pairs amplified PCR products that could form clear ssDNA (single strand DNA) bands through denaturation treatment. Ten SSCP markers had polymorphisms between 'Ning 7840' and 'Clark'. Five of the ten polymorphic SSCP markers were located on chromosome 3B by nulli-tetrasomic analysis. Three SSCP markers (Xsscp6, Xsscp20, and Xsscp21) were mapped into the region between Xgwm493 and Xgwm533, and possessed higher coefficient of determination (R2) than Xgwm493 and Xgwm533. The SSCP markers, Xsscp6, Xsscp20, and Xsscp21, can be used for map-based cloning of the QTL and for marker-assisted selection in FHB resistance breeding.

Quantitative trait loci for Fusarium head blight resistance in a recombinant inbred population of Wangshuibai/Wheaton.

Use of diverse sources of Fusarium head blight (FHB)-resistant germplasm in breeding may significantly improve wheat resistance to FHB. Wangshuibai is an FHB-resistant Chinese landrace unrelated to cv. Sumai 3, the most commonly used FHB-resistant source. In all, 139 F(6) recombinant inbred lines were developed from a cross between Wangshuibai and an FHB-susceptible cultivar, Wheaton, to map quantitative trait loci (QTL) for wheat resistance to initial infection (type I resistance), spread of FHB symptoms within a spike (type II resistance), and deoxynivalenol (DON) accumulation (type III resistance) in infected grain. The experiments were conducted in a greenhouse at Manhattan, KS from 2003 to 2005. More than 1,300 simple-sequence repeat and amplified fragment length polymorphism markers were analyzed in this population. Five QTL for type I resistance were detected on chromosomes 3AS, 3BS, 4B, 5AS, and 5DL after spray inoculation; seven QTL for type II resistance were identified on chromosomes 1A, 3BS, 3DL, 5AS, 5DL, and 7AL after point inoculation; and seven QTL for type III resistance were detected on chromosomes 1A, 1BL, 3BS, 5AS, 5DL, and 7AL with the data from both inoculation methods. These QTL jointly explained up to 31.7, 64, and 52.8% of the phenotypic variation for the three types of FHB resistance, respectively. The narrow-sense heritabilities were low for type I resistance (0.37 to 0.41) but moderately high for type II resistance (0.45 to 0.61) and type III resistance (0.44 to 0.67). The QTL on the distal end of 3BS, 5AS, and 5DL contributed to all three types of resistance. Two QTL, on 7AL and 1A, as well as one QTL near the centromere of 3BS (3BSc), showed effects on both type II and type III resistance. Selection for type II resistance may simultaneously improve type I and type III resistance as well. The QTL for FHB resistance identified in Wangshuibai have potential to be used to pyramid FHB-resistance QTL from different sources.

Trend of anti-tuberculosis drug resistance in Korea, 1994-2004.

SETTING: The 245 health centres through which the National Tuberculosis Programme (NTP) is implemented in Korea and the TB Laboratory Network of the Korean National Tuberculosis Association. OBJECTIVE: To observe the trend of anti-tuberculosis drug resistance in Korea from 1994 to 2004 and possible related factors. DESIGN: All tuberculosis (TB) patients registered for treatment at the health centres for a given period were assessed. RESULTS: Of 2636 new smear-positive patients from the 2004 survey, 338 cases (12.8%, 95% confidence interval [CI] 11.5-14.1) showed resistance to any of the first-line drugs: 261 with isoniazid (INH) resistance (9.9%, 95%CI 8.8-11.0) and 71 with multidrug resistance (MDR) (2.7%, 95%CI 2.1-3.3). Compared with previous surveys, a statistically significant increase in MDR (P=0.00675), any drug resistance (P=0.03779), any INH resistance (P=0.00313) and any rifampicin resistance (P = 0.00176) has been observed among new cases since 1994. Any resistance to second-line drugs ranged from 0.1% (capreomycin) to 1.1% (para-aminosalicylic acid) among new cases and from 1.1% to 3.6% among retreatment cases. Resistance to kanamycin and ofloxacin was found in 1.4% and 2.6%, respectively, of new and previously treated MDR-TB cases. CONCLUSION: A statistically significant increase in drug resistance was noticed among new cases.

An Internet-based surveillance system for tuberculosis in Korea.

SETTING: The Korea Tuberculosis Surveillance (KTBS) network includes 248 health centres throughout the country, as well as other public and private health institutions. OBJECTIVE: To develop a web-based surveillance system for tuberculosis (TB) and to monitor implementation of the National TB Control Programme (NTP) on an ongoing basis. DESIGN: A TB notification form was developed with new case definitions, and standardised to obtain uniform essential information of the cases with ease and speed. Data collection, compilation, analysis and feedback were made available at every level of the health authority via the Internet without restrictions of time and space. RESULTS: The Internet-based surveillance system was successfully implemented across the country, providing real-time national figures of TB using different variables-patient, time, area, site and type of disease--and facilitating on-line evaluation of NTP implementation. CONCLUSION: The web-based surveillance system has been well established within the existing health infrastructure, providing real-time figures on the TB burden. However, it requires continued improvement of the quality of information and of case reporting activities.

Quantitative trait loci for yield and related traits in the wheat population Ning7840 x Clark.

Grain yield and associated agronomic traits are important factors in wheat (Triticum aestivum L.) improvement. Knowledge regarding the number, genomic location, and effect of quantitative trait loci (QTL) would facilitate marker-assisted selection and the development of cultivars with desirable characteristics. Our objectives were to identify QTLs directly and indirectly affecting grain yield expression. A population of 132 F12 recombinant inbred lines (RILs) was derived by single-seed descent from a cross between the Chinese facultative wheat Ning7840 and the US soft red winter wheat Clark. Phenotypic data were collected for 15 yield and other agronomic traits in the RILs and parental lines from three locations in Oklahoma from 2001 to 2003. Twenty-nine linkage groups, consisting of 363 AFLP and 47 SSR markers, were identified. Using composite interval mapping (CIM) analysis, 10, 16, 30, and 14 QTLs were detected for yield, yield components, plant adaptation (shattering and lodging resistance, heading date, and plant height), and spike morphology traits, respectively. The QTL effects ranged from 7 to 23%. Marker alleles from Clark were associated with a positive effect for the majority of QTLs for yield and yield components, but gene dispersion was the rule rather than the exception for this RIL population. Often, QTLs were detected in proximal positions for different traits. Consistent, co-localized QTLs were identified in linkage groups 1AL, 1B, 4B, 5A, 6A, and 7A, and less consistent but unique QTLs were identified on 2BL, 2BS, 2DL, and 6B. Results of this study provide a benchmark for future efforts on QTL identification for yield traits.

Molecular characterization of a powdery mildew resistance gene in wheat cultivar suwon 92.

ABSTRACT Powdery mildew, caused by Blumeria graminis f. sp tritici, is an important foliar disease of wheat worldwide. Pyramiding race-specific genes into a single cultivar and combining race-specific resistance genes with durable resistance genes are the preferred strategies to improve the durability of powdery mildew resistance. The objectives of this study were to characterize a powdery mildew resistance gene in Suwon 92 and identify gene-specific or tightly linked molecular markers for marker-assisted selection (MAS). A population of recombinant inbred lines (RILs) was derived by single seed descent from a cross between Suwon 92 and a susceptible cultivar, CI 13227. The RILs were screened for adult-plant infection type of powdery mildew and characterized with amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) markers. The linked markers explained 41.3 to 69.2% of the phenotypic variances measured in 2 years. A morphological marker, hairy glume, was also associated with powdery mildew resistance in Suwon 92, and explained 43 to 51% of the phenotypic variance. The powdery mildew resistance gene in Suwon 92 was located on the short arm of chromosome 1A where Pm3 was located. Two gene-specific markers were developed based on the sequence of the cloned Pm3b gene. These two markers, which were mapped at the same locus in the peak region of the LOD score for the RIL population, explained most of the phenotypic variance for powdery mildew resistance in the RIL population. The powdery mildew resistance in Suwon 92 is most likely conditioned by the Pm3 locus. The gene markers developed herein can be directly used for MAS of some of the Pm3 alleles in breeding programs.

Main effects, epistasis, and environmental interactions of quantitative trait Loci for fusarium head blight resistance in a recombinant inbred population.

ABSTRACT Chinese Spring Sumai 3 chromosome 7A disomic substitution line (CS-SM3-7ADS) is highly resistant to Fusarium head blight (FHB), and an F(7) population of recombinant inbred lines derived from the cross CS-SM3-7ADS x Annong 8455 was evaluated for resistance to FHB to investigate main effects, epistasis, and environmental interactions of quantitative trait loci (QTLs) for FHB resistance. A molecular linkage map consists of 501 simple sequence repeat and amplified fragment length polymorphism markers. A total of 10 QTLs were identified with significant main effects on the FHB resistance using MapQTL and QTLMapper software. Among them, CS-SM3-7ADS carries FHB-resistance alleles at five QTLs on chromosomes 2D, 3B, 4D, and 6A. One QTL on 3BS had the largest effect and explained 30.2% of the phenotypic variance. Susceptible QTLs were detected on chromosomes 1A, 1D, 4A, and 4B. A QTL for enhanced FHB resistance was not detected on chromosome 7A of CS-SM3-7ADS; therefore, the increased FHB resistance in CS-SM3-7ADS was not due to any major FHB-resistance QTL on 7A of Sumai 3, but more likely was due to removal of susceptible alleles of QTLs on 7A of Chinese Spring. QTLMapper detected nine pairs of additive-additive interactions at 17 loci that explained 26% phenotypic variance. QTL-environment interactions explained 49% of phenotypic variation, indicating that the environments significantly affected the expression of the QTLs, especially these epistasis QTLs. Adding FHB-enhancing QTLs or removal of susceptible QTLs both may significantly enhance the degree of wheat resistance to FHB in a wheat cultivar.

Recovery rate of NTM from AFB smear-positive sputum specimens at a medical centre in South Korea.

OBJECTIVE: To investigate the recovery rate of non-tuberculous mycobacteria (NTM) from acid-fast bacilli (AFB) smear-positive sputum specimens at a tertiary care medical centre in South Korea with a high pulmonary tuberculosis (PTB) burden. DESIGN: Retrospective analysis of data from AFB smear- and culture-positive sputum specimens collected between January 1998 and December 2001. RESULTS: Over 4 years, 1328 sputum specimens collected from 616 patients were AFB smear- and culture-positive. NTM were recovered from 9.1% (121/1328) of the smear-positive sputum specimens, and from 8.1% (50/616) of patients with smear-positive sputum. NTM were isolated at least twice in 94% (47/50) of the patients from whom NTM was recovered. The most common organism found was Mycobacterium avium complex, followed by M. abscessus. CONCLUSION: These results suggest that a substantial proportion of patients at a tertiary care medical centre in South Korea with AFB smear-positive sputum specimens may have NTM lung disease rather than PTB.

Molecular mapping of a quantitative trait locus for aluminum tolerance in wheat cultivar Atlas 66.

Genetic improvement of aluminum (Al) tolerance is one of the cost-effective solutions to improve wheat (Triticum aestivum) productivity in acidic soils. The objectives of the present study were to identify quantitative trait loci (QTL) for Al-tolerance and associated PCR-based markers for marker-assisted breeding utilizing cultivar Atlas 66. A population of recombinant inbred lines (RILs) from the cross Atlas 66/Century was screened for Al-tolerance by measuring root-growth rate during Al treatment in hydroponics and root response to hematoxylin stain of Al treatment. After 797 pairs of SSR primers were screened for polymorphisms between the parents, 131 pairs were selected for bulk segregant analysis (BSA). A QTL analysis based on SSR markers revealed one QTL on the distal region of chromosome arm 4DL where a malate transporter gene was mapped. This major QTL accounted for nearly 50% of the phenotypic variation for Al-tolerance. The SSR markers Xgdm125 and Xwmc331 were the flanking markers for the QTL and have the potential to be used for high-throughput, marker-assisted selection in wheat-breeding programs.

Mapping of QTLs prolonging the latent period of Puccinia triticina infection in wheat.

Slow rusting is considered a crucial component of durable resistance to wheat leaf rust caused by Puccinia triticina and is often expressed in the form of a prolonged latent period. Selection for a longer latent period is considered an effective approach to developing wheat cultivars with improved durable resistance to leaf rust. A recombinant inbred line (RIL) population derived from CI 13227 (long latent period) x Suwon 92 (short latent period) was phenotyped for latent period in two greenhouse experiments in separate years, and amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) markers were analyzed in the same population. Among the RILs, the frequency distribution for latent period was continuous, and latent period was highly correlated between years (r=0.94, P<0.0001). A quantitative trait locus (QTL) prolonging the latent period of P. triticina, designated as QLrlp.osu-2DS, explained 42.8% and 54.5% of the phenotypic and genetic variance in the two experiments, respectively. QLrlp.osu-2DS was mapped on the distal region of chromosome 2DS. Two other QTLs for latent period, QLrlp.osu-2B and QLrlp.osu-7BL, were localized on chromosome 2B and the long arm of chromosome 7B, respectively. Multiple regression analysis showed that these three QTLs collectively explained 58.0% and 73.8% of the phenotypic and genetic variance over two experiments, respectively. Fourteen RILs that carried all three alleles for long latent period at three AFLP loci flanking QLrlp.osu-2DS, QLrlp.osu-2B, and QLrlp.osu-7BL had a mean latent period of 12.5 days, whereas 13 RILs without any long-latent-period alleles at the corresponding loci had a mean latent period of 7.4 days. Three SSR markers closely linked to these QTLs have potential to be applied in marker-assisted selection for prolonged latent period in wheat.

AFLP analysis of Cynodon dactylon (L.) Pers. var. dactylon genetic variation.

Cynodon dactylon (L.) Pers. var. dactylon (common bermudagrass) is geographically widely distributed between about lat 45 degrees N and lat 45 degrees S, penetrating to about lat 53 degrees N in Europe. The extensive variation of morphological and adaptive characteristics of the taxon is substantially documented, but information is lacking on DNA molecular variation in geographically disparate forms. Accordingly, this study was conducted to assess molecular genetic variation and genetic relatedness among 28 C. dactylon var. dactylon accessions originating from 11 countries on 4 continents (Africa, Asia, Australia, and Europe). A fluorescence-labeled amplified fragment length polymorphism (AFLP) DNA profiling method was used to detect the genetic diversity and relatedness. On the basis of 443 polymorphic AFLP fragments from 8 primer combinations, the accessions were grouped into clusters and subclusters associating with their geographic origins. Genetic similarity coefficients (SC) for the 28 accessions ranged from 0.53 to 0.98. Accessions originating from Africa, Australia, Asia, and Europe formed major groupings as indicated by cluster and principal coordinate analysis. Accessions from Australia and Asia, though separately clustered, were relatively closely related and most distantly related to accessions of European origin. African accessions formed two distant clusters and had the greatest variation in genetic relatedness relative to accessions from other geographic regions. Sampling the full extent of genetic variation in C. dactylon var. dactylon would require extensive germplasm collection in the major geographic regions of its distributional range.

The treatment of tuberculosis in South Korea.

South Korea's complex system of tuberculosis control has never been fully described. The prevalence of tuberculosis has dropped dramatically since 1965, partly because of farsighted governmental policy that provided low-cost, accessible tuberculosis treatment to the entire population. Within the tuberculosis control system, public and private sector entities provide a wide variety of treatment options. The National Tuberculosis Program focuses on improving cure rates for new cases, while the private sector has taken more of a role in the treatment of drug-resistant tuberculosis and other types of complicated cases. There has been a decrease in drug-resistant tuberculosis since 1980 for multiple reasons, including increased cure rates from the introduction of rifampin-based regimens, improved nutrition and living standards, and the treatment of drug-resistant cases in the private sector. Multidrug-resistant tuberculosis, however, still poses a significant threat to public health. The limited outcomes data that exist in South Korea for multidrug-resistant tuberculosis treatment suggest that cure rates are low and failure and abandonment rates are high. New public health measures are needed to improve the control of multidrug-resistant tuberculosis.

AFLP and STS tagging of a major QTL for Fusarium head blight resistance in wheat.

Large-scale field screening for Fusarium head blight (FHB) resistance in wheat is difficult because environmental factors strongly influences the expression of resistance genes. Marker-assisted selection (MAS) may provide a powerful alternative. Conversion of amplified fragment length polymorphism (AFLP) markers into sequence-tagged site (STS) markers can generate breeder-friendly markers for MAS. In a previous study, one major quantitative trait locus (QTL) on chromosome 3BS was identified by using EcoRI-AFLP and a recombinant inbred population derived from the cross Ning 7840/Clark. Further mapping with PstI-AFLPs identified five markers that were significantly associated with the QTL. Three of them individually explained 38% to 50% of the phenotypic variation for FHB resistance. Two of them (pAGT/mCTG57, pACT/mCTG136) were linked to the QTL in coupling, and another (pAG/mCAA244) was linked to the QTL in repulsion. Successful conversion of one AFLP marker (pAG/mCAA244) yielded a co-dominant STS marker that explains about 50% of the phenotypic variation for FHB resistance in the population. The STS was validated in 14 other cultivars and is the first STS marker for a FHB resistance QTL converted from an AFLP marker.

Deoxynivalenol-nonproducing fusarium graminearum causes initial infection, but does not cause disease spread in wheat spikes.

Fusarium graminearum is a major pathogen that causes fusarium head blight (FHB) in wheat and produces deoxynivalenol (DON) in infected grain. In previous studies, the trichodiene synthase gene (Tri5) in the fungal strain GZ3639 was disrupted to produce the DON-nonproducing strain GZT40. In this report, the virulence of strains GZ3639 and GZT40 was tested on wheat cultivars with various resistance levels by using methods of spray inoculation and injection inoculation with fungal conidia. Under field and greenhouse conditions, strain GZ3639 produced significantly more disease symptoms and reduced more yield than strain GZT40 in all wheat cultivars tested. Conidia of strain GZT40 germinated and infected inoculated spikelets, but disease symptoms were limited to inoculated spikelets without spread to uninoculated spikelets. When strain GZT40 was inoculated using the spray method, multiple initial infection sites in a spike resulted in higher levels of disease symptoms than in spikes inoculated by a single injection. Greenhouse tests confirmed that strain GZT40 did not produce DON in the infected kernels following either inoculation method. The results confirm that DON production plays a significant role in the spread of FHB within a spike, and are the first report that DON production is not necessary for initial infection by the fungus.

Cross-resistance between rifampicin and KRM-1648 is associated with specific rpoB alleles in Mycobacterium tuberculosis.

KRM-1648 resistant Mycobacterium tuberculosis strains were identified from a collection of rifampicin-resistant strains. Several strains had novel rpoB gene mutations in codons 512, 529 and 533 of the rpoB gene. The strains with mutations in codons 526 or 531, major mutation sites in rifampicin-resistant M. tuberculosis, were resistant to KRM-1648. Also, the strains with other mutations in the rpoB gene that were initially susceptible to KRM-1648 were prone to developing KRM-1648 resistance after further mutation. Thus, KRM-1648 is unlikely to be useful for the treatment of rifampicin-resistant tuberculosis.