<i>Mycobacterium bovis</i>BCG Immunization Induces Protective Immunity against Nine Different<i>Mycobacterium tuberculosis</i>Strains in Mice

Jeon, Bo Young; Derrick, Steven C.; Lim, Jae-Hyun; Kolibab, Kristopher; Dheenadhayalan, Veerabadran; Yang, Amy; Kreiswirth, Barry N.; Morris, Sheldon L.

doi:10.1128/iai.00019-08

Cited by 72 publications

(73 citation statements)

References 43 publications

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“…Combining analysis of published reports determining virulence of the Beijing strains, that were further discriminated as strains of modern or ancient Beijing sublineages, allows comparison of larger samples of the characterized strains of each sublineage. The strains determined in earlier studies as highly virulent, including strains HN878, W10, 210, and SA161 (31,32,33,34) were further identified as strains of the modern Beijing sublineage (35), whereas the less virulent strains, such as strains NHN5 and N4 (31,34), belonged to the ancient sublineage (35,36). In accordance with these observations, some isolates of a recently evolved modern Beijing sublineage (sublineage 7, RD150 group) were more virulent in mice than the ancient strains (8).…”

Section: Discussionsupporting

confidence: 69%

Mycobacterium tuberculosis Strains of the Modern Sublineage of the Beijing Family Are More Likely To Display Increased Virulence than Strains of the Ancient Sublineage

Gomes²,

et al. 2014

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dStrains of the Beijing genotype family of Mycobacterium tuberculosis are a cause of particular concern because of their increasing dissemination in the world and their association with drug resistance. Phylogenetically, this family includes distinct ancient and modern sublineages. The modern strains, contrary to the ancestral counterparts, demonstrated increasing prevalence in many world regions that suggest an enhanced bacterial pathogenicity. We therefore evaluated virulence of modern versus ancient Beijing strains with similar epidemiological and genotype characteristics. For this, we selected six strains that had very similar 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing profiles and belonged to the region of difference 181 (RD181) subgroup but differed using markers (mutT2 and mutT4 genes and NTF locus) that discriminate between modern and ancient Beijing sublineages. The strains were isolated from native patients in Brazil and Mozambique, countries with a low prevalence of Beijing strains. The virulence levels of these strains were determined in models of pulmonary infection in mice and in vitro macrophage infection and compared with that of a strain from Russia, part of the epidemic and hypervirulent Beijing clone B0/W148, and of the laboratory strain H37Rv. The results showed that two of the three modern Beijing strains were highly pathogenic, exhibiting levels of virulence comparable with that of the epidemic Russian strain. In contrast, all isolates of the ancient sublineage displayed intermediate or low virulence. The data obtained demonstrate that the strains of the modern Beijing sublineage are more likely to exhibit highly virulent phenotypes than ancient strains and suggest that genetic alterations characteristic of the modern Beijing sublineage favor selection of highly virulent bacteria. Despite extensive surveillance, tuberculosis (TB) remains a serious public health problem. In different parts of the world, there is concern about TB caused by the East Asian/Beijing lineage of Mycobacterium tuberculosis, demonstrating increasing prevalence in the global M. tuberculosis population (1). Clinical and epidemiological studies demonstrated that emergence of the Beijing strains could be associated with high levels of bacterial resistance to multiple drugs (2, 3) and enhanced pathogenicity of these strains, leading to increased transmissibility (4) and rapid progression from infection to active disease (5). However, the data on evaluation of the virulence of Beijing isolates were inconclusive, demonstrating a wide range of inflammatory and virulence phenotypes, as determined in animal models (6,7,8) and in vitro models of macrophage infection (9, 10).Such differences in the virulence of Beijing strains could be associated with genetic heterogeneity of the Beijing M. tuberculosis lineage. Indeed, bacterial genotyping and sequencing demonstrated that the Beijing lineage, having in common a characteristic spoligotype signature and lack of the region ...

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Section: Discussionsupporting

confidence: 69%

Mycobacterium tuberculosis Strains of the Modern Sublineage of the Beijing Family Are More Likely To Display Increased Virulence than Strains of the Ancient Sublineage

Gomes²,

et al. 2014

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“…Beijing has been regarded as an emerging genotype on the basis of its global distribution, its association with young age (4), and its proportional increase in prevalence over time (8,39). An increased ability to circumvent the protection afforded by BCG vaccination is suggested by the positive association (of the Beijing genotype) with the presence of a BCG scar in human populations (4) and has been observed in mice (24), although more recent findings challenge this observation (20). Multiple mechanisms have been explored to explain the potential link between the emergence of the Beijing genotype and low-level BCG protection (1), which may provide the Beijing genotype with a selective advantage in populations in which universal BCG vaccination is practiced.…”

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confidence: 67%

Mycobacterium tuberculosis Transmission Is Not Related to Household Genotype in a Setting of High Endemicity

et al. 2009

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Among the different strains of Mycobacterium tuberculosis, Beijing has been identified as an emerging genotype. Enhanced transmissibility provides a potential mechanism for genotype selection. This study evaluated whether the Beijing genotype is more readily transmitted than other prevalent genotypes to children in contact with an adult tuberculosis (TB) index case in the child's household. We conducted a prospective, community-based study at two primary health care clinics in Cape Town, South Africa, from January 2003 through December 2004. Bacteriologically confirmed new adult pulmonary TB cases were genotyped by IS6110 DNA fingerprinting; household contacts less than 5 years were traced and screened for M. tuberculosis infection and/or disease. A total of 187 adult index cases were identified from 174 households with children aged less than 5 years. Of 261 child contacts aged 0 to 5 years, 219 (83.9%) were completely evaluated and the isolate from the index case was successfully genotyped. M. tuberculosis infection (induration of >10 mm by Mantoux tuberculin skin test) was documented in 118/219 (53.9%) children; 34 (15.5%) had radiographic signs suggestive of active TB. There was no significant difference in the ratio of infected children among those exposed to the Beijing genotype (51/89; 57.3%) and those exposed to non-Beijing genotypes (55/115; 47.8%) (odds ratio, 1.5; 95% confidence interval, 0.8 to 2.7). Genotyping was successful for six children diagnosed with active TB; the isolates from only two children had IS6110 fingerprints that were identical to the IS6110 fingerprint of the isolate from the presumed index case. We found no significant association between the M. tuberculosis genotype and transmissibility within the household. However, undocumented M. tuberculosis exposure may have been a major confounding factor in this setting with a high burden of TB.

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“…In addition, persons treated for tuberculosis with antimycobacterial drugs can be reinfected and develop disease (36). This is also true in animal models (8,16,32). This suggests that memory responses generated during previous mycobacterial infections are not generally capable of protecting against new infections or disease.…”

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confidence: 83%

Cytotoxicity and Secretion of Gamma Interferon Are Carried Out by Distinct CD8 T Cells duringMycobacterium tuberculosisInfection

2009

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The host immune response is generally sufficient to contain Mycobacterium tuberculosis infection. It does not, however, efficiently prevent subsequent infection with M. tuberculosis or provide sterilizing immunity. While the understanding of the immune response generated against this pathogen is incomplete, improvements have been achieved due to advances in immunological tools. In this study, we analyzed the multifunctional nature of primary and memory CD8 T-cell responses generated during murine M. tuberculosis infection. We generated a recombinant M. tuberculosis strain expressing ovalbumin (OVA) epitopes in order to expand the peptides for the detection of CD8 T cells during M. tuberculosis infection and enable us to use OVA-specific reagents. Our results indicate that the majority of M. tuberculosis-specific CD8 T cells are limited to either cytotoxicity or the secretion of gamma interferon (IFN-␥), with cytotoxicity being far more prevalent than IFN-␥ secretion. Memory CD8 T cells responded earlier and reached higher levels in the lungs than naïve CD8 T cells, as was expected. They were, however, less cytotoxic and secreted less IFN-␥ than newly primed CD8 T cells, suggesting that one factor contributing to bacterial persistence and lack of sterilizing immunity may be the low quality of memory cells that are generated.

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Mycobacterium bovisBCG Immunization Induces Protective Immunity against Nine DifferentMycobacterium tuberculosisStrains in Mice

Cited by 72 publications

References 43 publications

Mycobacterium tuberculosis Strains of the Modern Sublineage of the Beijing Family Are More Likely To Display Increased Virulence than Strains of the Ancient Sublineage

Mycobacterium tuberculosis Strains of the Modern Sublineage of the Beijing Family Are More Likely To Display Increased Virulence than Strains of the Ancient Sublineage

Mycobacterium tuberculosis Transmission Is Not Related to Household Genotype in a Setting of High Endemicity

Cytotoxicity and Secretion of Gamma Interferon Are Carried Out by Distinct CD8 T Cells duringMycobacterium tuberculosisInfection

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