Whole-Genome Sequencing for Rapid Susceptibility Testing of <i>M. tuberculosis</i>

Köser, Claudio U.; Bryant, Josephine M.; Becq, Jennifer; Török, M. Estée; Ellington, Matthew J.; Martí‐Renom, Marc A.; Carmichael, Andrew; Parkhill, Julian; Smith, Geoffrey; Peacock, Sharon J.

doi:10.1056/nejmc1215305

Cited by 198 publications

(151 citation statements)

References 5 publications

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“…Mixed-infection by both strains that might affect the immune responses was not addressed because of lack of appropriate technology. Whole genome sequencing of mycobacteria grown directly from sputum is a very promising approach [35,36]. Adjustment for multiple testing analyses was not applied on the p-values, although some might become nonsignificant after adjusting, it is unlikely that this would affect the consistent trend of the result we presented.…”

Section: Discussionmentioning

confidence: 99%

Differences in T‐cell responses between Mycobacterium tuberculosis and Mycobacterium africanum‐infected patients

et al. 2014

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In The Gambia, Mycobacterium tuberculosis (Mtb) and Mycobacterium africanum (Maf) are major causes of tuberculosis (TB). Maf is more likely to cause TB in immune suppressed individuals, implying differences in virulence. Despite this, few studies have assessed the underlying immunity to the two pathogens in human. In this study, we analyzed T-cell responses from 19 Maf-and 29 Mtb-infected HIV-negative patients before and after TB chemotherapy following overnight stimulation of whole blood with TB-specific antigens. Before treatment, percentages of early secreted antigenic target-6(ESAT-6)/culture filtrate protein-10(CFP-10) and purified protein derivative-specific single-TNF-α-producing CD4 + and CD8 + T cells were significantly higher while single-IL-2-producing T cells were significantly lower in Maf-compared with Mtb-infected patients. Purified protein derivativespecific polyfunctional CD4 + T cells frequencies were significantly higher before than after treatment, but there was no difference between the groups at both time points. Furthermore, the proportion of CD3 + CD11b + T cells was similar in both groups pretreatment, but was significantly lower with higher TNF-α, IL-2, and IFN-γ production in Mtbcompared with that of Maf-infected patients posttreatment. Our data provide evidence of differences in T-cell responses to two mycobacterial strains with differing virulence, providing some insight into TB pathogenesis with different Mtb strains that could be prospectively explored as biomarkers for TB protection or susceptibility. Keywords: Cytokines r Mycobacterium africanum r Mycobacterium tuberculosis r T cells r TuberculosisAdditional supporting information may be found in the online version of this article at the publisher's web-site 1388 Leopold D. Tientcheu et al. Eur. J. Immunol. 2014. 44: 1387-1398 TB is caused by two distinct strains Mycobacterium africanum (Maf) and Mycobacterium tuberculosis (Mtb), with Maf causing up to half of all TB [2]. In The Gambia, TB patients infected with Maf West African type 2 are more likely to be older, HIV coinfected, and/or severely malnourished [3]. In addition, their exposed household contacts have a slower rate of progression to active disease compared with their Mtb-exposed counterparts [4], suggesting that Maf might be the less virulent of the two prevalent strains [5,6]. The heterogeneity in chest x-rays, bacillary load in sputum and clinical symptoms, likely reflects the variation in host immune response to the invading pathogen, and/or the differences between the lineages within the MTBC. For instance, Maf has slower growth in culture medium compared with Mtb [6,7], which may influence progression to active disease [4].The recently published genome of Maf reveals a high content of pseudogenes and the presence of a unique sequence -the region of difference 900 "RD900" that has been deleted evolutionarily from Mtb and M. bovis strains [8]. Many studies have concentrated on the pathogen strain differences in various geographical locations, with only a few anal...

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Section: Discussionmentioning

confidence: 99%

Differences in T‐cell responses between Mycobacterium tuberculosis and Mycobacterium africanum‐infected patients

et al. 2014

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“…145,146 However, before wholegenome sequencing information can be used in routine clinical practice, several important issues need to be resolved. Whole-genome sequencing is complicated by the need for culture before DNA extraction, 147 incomplete knowledge of all resistance-conferring mutations, 59,148 and the need for a validated pipeline to accurately predict resistance.…”

Section: The Lancet Respiratory Medicine Commissionmentioning

confidence: 99%

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

Dheda

Gumbo

Maartens

et al. 2017

The Lancet Respiratory Medicine

504

464

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“…The sensitivity of PCR-sequencing varies considerably according to the number and regions of drug resistance-associated loci included for each drug and the frequency of specific mutations in these loci at different geographical locations/ethnic groups of TB patients [42,43,48,[53][54][55]. However, this approach is time consuming and technically demanding and is being rapidly replaced by whole genome sequencing [14,46,48].…”

mentioning

confidence: 99%

Why Phenotypic Drug Susceptibility Testing of Mycobacterium tuberculosis to First-Line Drugs is not Sufficient for Proper Management of Drug-Resistant and Multidrug-Resistant tuberculosis?

Ahmad¹

2017

J Bacteriol Parasitol

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Whole-Genome Sequencing for Rapid Susceptibility Testing of M. tuberculosis

Cited by 198 publications

References 5 publications

Differences in T‐cell responses between Mycobacterium tuberculosis and Mycobacterium africanum‐infected patients

Differences in T‐cell responses between Mycobacterium tuberculosis and Mycobacterium africanum‐infected patients

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

Why Phenotypic Drug Susceptibility Testing of Mycobacterium tuberculosis to First-Line Drugs is not Sufficient for Proper Management of Drug-Resistant and Multidrug-Resistant tuberculosis?

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