ESAT‐6 and CFP‐10 in Clinical versus Environmental Isolates of<i>Mycobacterium kansasii</i>

Arend, Sandra M.; Haas, Petra de; Leyten, Eliane M. S.; Rosenkrands, Ida; Rigouts, Leen; Andersen, Peter; Mijs, Wouter; Dissel, Jaap T. van; Soolingen, Dick van

doi:10.1086/428950

Cited by 50 publications

(41 citation statements)

References 43 publications

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“…Previous authors have recorded the presence of RD1 in M. flavescens (1). We were unable to demonstrate it in four reference strains (ATCC 23008, ATCC 23033, ATCC 23035, and ATCC 23039) and a clinical isolate.…”

contrasting

confidence: 76%

“…1). Moreover, M. kansasii, M. szulgai, and M. marinum are considered the most pathogenic among the NTM (1,6,16). Therefore, RD1 may play a role in virulence of these NTM.…”

mentioning

confidence: 99%

“…The RD1 sequences differed between M. kansasii type 1, an important causative agent of NTM disease, and the other types, which are less involved or not involved in human disease (1). Clinically relevant and nonrelevant M. szulgai isolates, determined using the American Thoracic Society diagnostic criteria (6,16), shared identical sequences.…”

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confidence: 99%

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Region of Difference 1 in Nontuberculous Mycobacterium Species Adds a Phylogenetic and Taxonomical Character

et al. 2009

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The esat-6 and cfp-10 genes are essential for virulence in Mycobacterium tuberculosis. Among nontuberculous mycobacteria, we found these genes only in M. kansasii, M. szulgai, M. marinum, and M. riyadhense, with unique sequences. This adds a phylogenetic and taxonomical characteristic and may represent a virulence factor for nontuberculous mycobacteria.The 6-kDa early secretory antigenic target (ESAT-6) and 10-kDa culture filtrate protein (CFP-10) of Mycobacterium tuberculosis are potent T-cell antigens (2, 12). The genes encoding ESAT-6 and CFP-10 are situated within "region of difference 1" (RD1) of Mycobacterium tuberculosis but are also present in some nontuberculous mycobacteria (NTM) (2, 12). Deletion of RD1 in M. tuberculosis significantly decreases its virulence in animal models (8), suggesting that genes residing in RD1 are involved in pathogenesis. In M. tuberculosis, the RD1 proteins effect translocation to the cytosol, a mechanism for survival within macrophages (15). Therefore, RD1 in NTM may also play a crucial role in virulence.To improve our understanding of the pathogenesis of NTM disease and the possible role of RD1 in virulence, we screened a wide diversity of NTM for the presence of RD1.From our laboratory database, we retrieved isolates of all five Mycobacterium kansasii subtypes based on 16S-23S internal transcribed spacer sequencing (n ϭ 15),M. riyadhense (n ϭ 1), and M. tuberculosis H37Rv.The selection of these strains was based on their phylogenetic relationship with the M. tuberculosis complex in the multigene taxonomical model published by Devulder et al. (3).To establish the presence of an RD1-like element and sequences of the esat-6 and cfp-10 genes, we used the Esa-12 (CATGACAGAGCAGCAGTG) and Esa-303 (5Ј-GCCCT ATGCGAACATCCC-3Ј) primers for esat-6 and the opBR78 (5Ј-GTAGCCCGGGATGGCAGAGATGAAGACCGATGC C-3Ј) and opBR103 (5Ј-TCAGAAGCCCATTTGCGAGGAC AGC-3Ј) primers for cfp-10 (1). The M. smegmatis esat-6 and cfp-10 gene sequences were extracted from the whole-genome sequence in the GenBank database (accession number CP000480).Using these primers, we were able to demonstrate an RD1 (1). None of the PCRnegative species hybridized with either probe (data not shown). The presence of RD1, characterized by an esat-6-like gene and an cfp-10-like gene, is a phylogenetic characteristic among the NTM. It is mainly found only among slowly growing NTM species that are phylogenetically related to the M. tuberculosis complex based on the multigene taxonomical model by Devulder et al. (3) and in the more distantly related rapid grower M. smegmatis. Possibly, the presence of RD1 reflects phylogenetic relationships to the M. tuberculosis complex.Previous authors have recorded the presence of RD1 in M. flavescens (1). We were unable to demonstrate it in four reference strains (ATCC 23008, ATCC 23033, ATCC 23035, and ATCC 23039) and a clinical isolate. Thus, with its presence of an RD1 region, M. smegmatis still stands out among the rapid growing NTM.Gey van Pittius et al. have demonstrated the presence ...

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confidence: 76%

“…1). Moreover, M. kansasii, M. szulgai, and M. marinum are considered the most pathogenic among the NTM (1,6,16). Therefore, RD1 may play a role in virulence of these NTM.…”

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confidence: 99%

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Region of Difference 1 in Nontuberculous Mycobacterium Species Adds a Phylogenetic and Taxonomical Character

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“…Serum CFP-10 was detectable at lower concentrations than ESAT-6, perhaps owing to variable expression levels of ESAT-6 and CFP-10 in different strains of Mtb (40,41). However, host β2 microglobulin also has been reported to bind ESAT-6 to mask a tryptic cleavage site (amino acids 90-95) required for the 1,900.95 m/z ESAT-6 peptide (16,42), and thus may inhibit ESAT-6 cleavage to decrease the apparent serum ESAT-6 levels in our assay.…”

Section: Discussionmentioning

confidence: 97%

Quantification of circulating Mycobacterium tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring

Liu

Zhao

Fan

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Tuberculosis (TB) is a major global health threat, resulting in an urgent unmet need for a rapid, non-sputum-based quantitative test to detect active Mycobacterium tuberculosis (Mtb) infections in clinically diverse populations and quickly assess Mtb treatment responses for emerging drug-resistant strains. We have identified Mtb-specific peptide fragments and developed a method to rapidly quantify their serum concentrations, using antibody-labeled and energy-focusing porous discoidal silicon nanoparticles (nanodisks) and high-throughput mass spectrometry (MS) to enhance sensitivity and specificity. NanoDisk-MS diagnosed active Mtb cases with high sensitivity and specificity in a case-control study with cohorts reflecting the complexity of clinical practice. Similar robust sensitivities were obtained for cases of culture-positive pulmonary TB (PTB; 91.3%) and extrapulmonary TB (EPTB; 92.3%), and the sensitivities obtained for culture-negative PTB (82.4%) and EPTB (75.0%) in HIV-positive patients significantly outperformed those reported for other available assays. NanoDisk-MS also exhibited high specificity (87.1-100%) in both healthy and high-risk groups. Absolute quantification of serum Mtb antigen concentration was informative in assessing responses to antimycobacterial treatment. Thus, a NanoDisk-MS assay approach could significantly improve the diagnosis and management of active TB cases, and perhaps other infectious diseases as well.D espite international efforts and initiatives, tuberculosis (TB) remains a major public health concern worldwide, associated with high morbidity and mortality (1, 2). Detecting active TB cases and monitoring their responses to therapy are fraught with challenges, relying predominantly on microbiologic techniques that use sputum samples, including acid-fast Bacillus (AFB) smear microscopy-widely used as an initial test for TB diagnosis (3, 4)-and Mycobacterium tuberculosis (Mtb) culture, both of which have only moderate sensitivity and specificity and a long turnaround time (5, 6). Moreover, sputum samples are difficult to obtain after symptom improvement, and often are not diagnostically useful for extrapulmonary TB (EPTB) cases. The PCR-based Xpert MTB/RIF sputum assay was introduced to improve the speed and specificity of TB diagnosis, but this assay has poor sensitivity under low bacterial loads and cannot distinguish live and nonviable Mtb contributions (7,8). A recent World Health Organization (WHO) policy update acknowledged the low quality of evidence supporting the use of Xpert MTB/RIF to diagnose EPTB (9). Diagnostic challenges can be further magnified in patients coinfected with HIV and TB (10). In addition, none of these techniques provides quantitative results that can be used to monitor treatment effects (11,12).Consequently, there is an urgent need, highlighted as a high priority in a recent WHO consensus report (13), for the development of rapid, quantitative, non-sputum-based biomarker tests that do not require bacterial isolation to detect active TB (13). Non-s...

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“…However, NTM phylogenetically related to M. tuberculosis, such as M. kansasii, Mycobacterium marinum, Mycobacterium szulgai, Mycobacterium riyadhense and Mycobacterium gastri, also carry RD1 regions with variants of esat-6 and cfp-10 genes (Devulder et al, 2005;Gey van Pittius et al, 2006;van Ingen et al, 2009). For M. kansasii, ESAT-6 and CFP-10 antigens were observed in both clinical and environmental strains and they were responsible for T-cell cross-reactivity and positive IGRA responses (Arend et al, 2005;Kobashi et al, 2009aKobashi et al, , 2009b. This case thus illustrates a limit in the specificity of IGRAs due to the presence of shared antigens in several mycobacterial species, and strengthens the essential role for direct diagnostic methods, such as culture, for accurate differential diagnosis of TB and M. kansasii infection.…”

Section: Discussionmentioning

confidence: 99%

Temporal interferon-gamma release response to Mycobacterium kansasii infection in an anorexia nervosa patient

Cosson

Bertrand

Martin

et al. 2012

Journal of Medical Microbiology

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ESAT‐6 and CFP‐10 in Clinical versus Environmental Isolates ofMycobacterium kansasii

Cited by 50 publications

References 43 publications

Region of Difference 1 in Nontuberculous Mycobacterium Species Adds a Phylogenetic and Taxonomical Character

Region of Difference 1 in Nontuberculous Mycobacterium Species Adds a Phylogenetic and Taxonomical Character

Quantification of circulating Mycobacterium tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring

Temporal interferon-gamma release response to Mycobacterium kansasii infection in an anorexia nervosa patient

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