Low Induction of Proinflammatory Cytokines Parallels Evolutionary Success of Modern Strains within the Mycobacterium tuberculosis Beijing Genotype

Laarhoven, Arjan van; Mandemakers, Jornt J.; Kleinnijenhuis, Johanneke; Enaimi, Mimount; Lachmandas, Ekta; Joosten, Leo A. B.; Ottenhoff, Tom H. M.; Netea, Mihai G.; Soolingen, Dick van; Crevel, Reinout van

doi:10.1128/iai.00282-13

Cited by 52 publications

(50 citation statements)

References 38 publications

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“…Moreover, after several studies suggested enhanced ability of Beijing strains in general to circumvent BCG-vaccine induced immunity (13,14), one study reported that modern Beijing strains were isolated more frequently from BCG-vaccinated patients than nonvaccinated individuals (9). The observation that the interaction of modern Beijing strains with the immune system is different than that of ancient strains was further confirmed by a recent study that described differences in pro-inflammatory cytokine induction for both strains (32). If modern Beijing strains indeed have selective advantages over other M. tuberculosis strains and spread more prosperously, this should be reflected in the degree of genetic conservation.…”

supporting

confidence: 50%

Disclosure of Selective Advantages in the “modern” Sublineage of the Mycobacterium tuberculosis Beijing Genotype Family by Quantitative Proteomics

Keijzer

Haas

et al. 2014

Molecular & Cellular Proteomics

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The Mycobacterium tuberculosis Beijing genotype, consisting of the more ancient (atypical) and modern (typical) emerging sublineage, is one of the most prevalent and genetically conserved genotype families and has often been associated with multidrug resistance. In this study, we employed a 2D-LC-FTICR MS approach, combined with dimethylation of tryptic peptides, to systematically compare protein abundance levels of ancient and modern Beijing strains and identify differences that could be associated with successful spread of the modern sublineage. The data is available via ProteomeXchange using the identifier PXD000931. Despite the highly uniform protein abundance ratios in both sublineages, we identified four proteins as differentially regulated between both sublineages, which could explain the apparent increased adaptation of the modern Beijing strains. These proteins are; Rv0450c/ MmpL4, Rv1269c, Rv3137, and Rv3283/sseA. Transcriptional and functional analysis of these proteins in a large cohort of 29 Beijing strains showed that the mRNA levels of Rv0450c/MmpL4 are significantly higher in modern Beijing strains, whereas we also provide evidence that Rv3283/ sseA is less abundant in the modern Beijing sublineage. Our findings provide a possible explanation for the increased virulence and success of the modern Beijing sublineage. In addition, in the established dataset of 1817 proteins, we demonstrate the pre-existence of several, possibly unique, antibiotic efflux pumps in the proteome of the Beijing strains. This may reflect an increased ability of Beijing strains to escape exposure to antituberculosis drugs. Molecular & Cellular

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supporting

confidence: 50%

Disclosure of Selective Advantages in the “modern” Sublineage of the Mycobacterium tuberculosis Beijing Genotype Family by Quantitative Proteomics

Keijzer

Haas

et al. 2014

Molecular & Cellular Proteomics

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“…For example, a recent study showed "modern" Beijing caused more histopathological changes and mortality in mice (56). Most of all, three more recent studies all found that "modern" Beijing strains induced lower and/or delayed proinflammatory that may enable the bacteria to escape from host immune response (57)(58)(59). Epidemiologically, numerous studies from various geographical settings have suggested a higher transmissibility of "modern" Beijing genotype, as indicated by increased prevalence in young people (i.e., a proxy for ongoing transmission) (12,23,51,60), or a higher genotypic clustering proportion than "ancient" genotype (26,52,55).…”

Section: Discussionmentioning

confidence: 99%

Southern East Asian origin and coexpansion of Mycobacterium tuberculosis Beijing family with Han Chinese

Luò

Comas

Luo

et al. 2015

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

146

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The Beijing family is the most successful genotype of Mycobacterium tuberculosis and responsible for more than a quarter of the global tuberculosis epidemic. As the predominant genotype in East Asia, the Beijing family has been emerging in various areas of the world and is often associated with disease outbreaks and antibiotic resistance. Revealing the origin and historical dissemination of this strain family is important for understanding its current global success. Here we characterized the global diversity of this family based on whole-genome sequences of 358 Beijing strains. We show that the Beijing strains endemic in East Asia are genetically diverse, whereas the globally emerging strains mostly belong to a more homogenous subtype known as “modern” Beijing. Phylogeographic and coalescent analyses indicate that the Beijing family most likely emerged around 30,000 y ago in southern East Asia, and accompanied the early colonization by modern humans in this area. By combining the genomic data and genotyping result of 1,793 strains from across China, we found the “modern” Beijing sublineage experienced massive expansions in northern China during the Neolithic era and subsequently spread to other regions following the migration of Han Chinese. Our results support a parallel evolution of the Beijing family and modern humans in East Asia. The dominance of the “modern” Beijing sublineage in East Asia and its recent global emergence are most likely driven by its hypervirulence, which might reflect adaption to increased human population densities linked to the agricultural transition in northern China.

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“…In one of the earlier studies the differential host response seen in isolated MDM was not observed in peripheral blood mononuclear cells for different strains [10]. In contrast to this, Laarhoven et al reported a differential cytokine response to the strains in PBMC [29]. We compared the proinflammatory cytokine responses across the isolates and there was overall a statistically significant effect of certain lineages on the cytokine levels observed in whole blood assay.…”

Section: Discussionmentioning

confidence: 81%

Mycobacterium tuberculosis strains from ancient and modern lineages induce distinct patterns of immune responses

Chakraborty

Kulkarni

Rajan

et al. 2018

J Infect Dev Ctries

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Introduction: It is possible that the difference in virulence and prevalence of different strains of Mycobacterium tuberculosis is related to the diverse immune response they evoke in the host. Outbreak strains have been shown to subvert the innate immune response as a potential host evasion mechanism. However, the immunological outcome of the interactions of different clinical strains with different host cells is still not understood. Methodology: Extremely Drug Resistant (XDR) Beijing, a modern lineage clinical strain and a comparator ancient lineage strain, EAI-5, were selected for the present study. The early induction of proinflammatory cytokines in human peripheral blood monocyte derived macrophages (MDM), monocyte derived dendritic cells (MDDC) and whole blood (WB) infected by selected clinical isolates and laboratory strains H37Rv and BCG were assessed. Results: The two clinical strains exhibited distinct patterns of cytokine induction. The ancient lineage strain induced substantially higher expression of all proinflammatory cytokines like TNF-α, IL-1β, IL-12 and chemokines like MCP-1, IL-8. However, the modern lineage strain exhibited suppressed response for the same. Further, the immune responses to two strains were conserved in infected MDM, MDDC and WB i.e. showing similar patterns of response across multiple human hosts. However, the differential response pattern was not observed when bacterial sonicates were used instead of live mycobacteria. Conclusions: The lineage specific patterns in induction of proinflammatory cytokines and chemokines by different M. tuberculosis strains remain similar in macrophage and dendritic cells isolated from different individuals. The present study also confirms that whole cell sonicates of different lineages of M. tuberculosis fail to induce such lineage specific response.

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Low Induction of Proinflammatory Cytokines Parallels Evolutionary Success of Modern Strains within the Mycobacterium tuberculosis Beijing Genotype

Cited by 52 publications

References 38 publications

Disclosure of Selective Advantages in the “modern” Sublineage of the Mycobacterium tuberculosis Beijing Genotype Family by Quantitative Proteomics

Disclosure of Selective Advantages in the “modern” Sublineage of the Mycobacterium tuberculosis Beijing Genotype Family by Quantitative Proteomics

Southern East Asian origin and coexpansion of Mycobacterium tuberculosis Beijing family with Han Chinese

Mycobacterium tuberculosis strains from ancient and modern lineages induce distinct patterns of immune responses

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