First Succinyl-Proteome Profiling of Extensively Drug-Resistant Mycobacterium tuberculosis Revealed Involvement of Succinylation in Cellular Physiology

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

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Urgent Implementation in a Hospital Setting of a Strategy To Rule Out Secondary Cases Caused by Imported Extensively Drug-Resistant Mycobacterium tuberculosis Strains at Diagnosis

Journal of Clinical Microbiology ◽

10.1128/jcm.01718-16 ◽

2016 ◽

Vol 54 (12) ◽

pp. 2969-2974 ◽

Cited By ~ 10

Author(s):

Laura Pérez-Lago ◽

Miguel Martínez-Lirola ◽

Sergio García ◽

Marta Herranz ◽

Igor Mokrousov ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

High Risk ◽

Primary Cultures ◽

Hospital Setting ◽

Drug Resistant ◽

Nucleotide Polymorphisms ◽

Content Type ◽

Extensively Drug Resistant ◽

Incident Cases ◽

Rule Out

Current migratory movements require new strategies for rapidly tracking the transmission of high-risk importedMycobacterium tuberculosisstrains. Whole-genome sequencing (WGS) enables us to identify single-nucleotide polymorphisms (SNPs) and therefore design PCRs to track specific relevant strains. However, fast implementation of these strategies in the hospital setting is difficult because professionals working in diagnostics, molecular epidemiology, and genomics are generally at separate institutions. In this study, we describe the urgent implementation of a system that integrates genomics and molecular tools in a genuine high-risk epidemiological alert involving 2 independent importations of extensively drug resistant (XDR) and pre-XDR BeijingM. tuberculosisstrains from Russia into Spain. Both cases involved commercial sex workers with long-standing tuberculosis (TB). The system was based on strain-specific PCRs tailored from WGS data that were transferred to the local node that was managing the epidemiological alert. The optimized tests were available for prospective implementation in the local node 33 working days after receiving the primary cultures of the XDR strains and were applied to all 42 new incident cases. An interpretable result was obtained in each case (directly from sputum for 27 stain-positive cases) and corresponded to the amplification profiles for strains other than the targeted pre-XDR and XDR strains, which made it possible to prospectively rule out transmission of these high-risk strains at diagnosis.

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Predominance of Beijing genotype in extensively drug resistant Mycobacterium tuberculosis isolates from a tertiary care hospital in New Delhi, India

International Journal of Mycobacteriology ◽

10.1016/j.ijmyco.2013.03.001 ◽

2013 ◽

Vol 2 (2) ◽

pp. 109-113 ◽

Cited By ~ 4

Author(s):

Jyoti Arora ◽

Manpreet Bhalla ◽

Zeeshan Sidiq ◽

Prabha Lal ◽

Digamber Behera ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Tertiary Care Hospital ◽

Tertiary Care ◽

Beijing Genotype ◽

New Delhi ◽

Care Hospital ◽

Drug Resistant ◽

Extensively Drug Resistant

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Tuberculose Multirresistente por Estirpes da Família Beijing, em Doentes de Lisboa, Portugal: Estudo Preliminar

Acta Médica Portuguesa ◽

10.20344/amp.7882 ◽

2017 ◽

Vol 30 (3) ◽

pp. 175 ◽

Cited By ~ 2

Author(s):

Fernando Maltez ◽

Teresa Martins ◽

Diana Póvoas ◽

João Cabo ◽

Helena Peres ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Past History ◽

Multidrug Resistant ◽

Resistance Pattern ◽

Drug Resistant ◽

Beijing Family ◽

Resistant Tuberculosis ◽

Extensively Drug Resistant ◽

Number Of Patients ◽

Drug Resistant Strains

Introduction: Beijing family strains of Mycobacterium tuberculosis are associated with multidrug-resistance. Although strains of the Lisboa family are the most common among multidrug-resistant and extensively drug-resistant patients in the region, several studies have reported the presence of the Beijing family. However, the features of patients from whom they were isolated, are not yet known.Material and Methods: Retrospective study involving 104 multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis, from the same number of patients, isolated and genotyped between 1993 and 2015 in Lisbon. We assessed the prevalence of strains of both families and the epidemiologic and clinical features of those infected with Beijing family strains.Results: Seventy-four strains (71.2%) belonged to the Lisboa family, 25 (24.0%) showed a unique genotypic pattern and five (4.8%) belonged to the Beijing family, the latter identified after 2009. Those infected with Beijing family strains were angolan (n = 1), ukrainian (n = 2) and portuguese (n = 2), mainly young-aged and, four of five immunocompetent and with no past history of tuberculosis. All had multidrug-resistant tuberculosis. We did not find any distinctive clinical or radiological features, neither a predominant resistance pattern. Cure rate was high (four patients).Discussion: Although the number of infected patients with Beijing strains was small, it suggests an important proportion of primary tuberculosis, a potential for transmission in the community but also a better clinical outcome when compared to other reported strains, such as W-Beijing and Lisboa.Conclusion: Although Lisboa family strains account for most of the multidrug and extensively drug-resistant tuberculosis cases in Lisbon area, Beijing strains are transmitted in the city and might change the local characteristics of the epidemics.

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