Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations

Abdallah, Abdallah; Hill-Cawthorne, Grant A.; Otto, Thomas D.; Coll, Francesc Español i; Guerra-Assunção, José Afonso; Gao, Ge; Naeem, Raeece; Ansari, Hifzur Rahman; Malas, Tareq B.; Adroub, Sabir A.; Verboom, Theo; Ummels, Roy; Zhang, Huoming; Panigrahi, Aswini K.; McNerney, Ruth; Brosch, Roland; Clark, Taane G.; Behr, Marcel A.; Bitter, Wilbert; Pain, Arnab

doi:10.1038/srep15443

Cited by 86 publications

(132 citation statements)

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“…The differential expression of 23 proteins implicated in virulence were confirmed by SRM in seven clinically relevant strains showing various degrees of pathogenicity [51]. Proteomic and transcriptional analyses also generated some insights on metabolic remodeling between different BCG strains which might be manifested by various degrees of immunogenicity and potentially vaccine efficacy [52]. The mycobacterial protein analysis of mono- and HIV co-infected macrophages revealed 92 significant changes which belong to various functional categories such as toxin-antitoxin (TA) modules, cation transporters and type VII (Esx) secretion systems [53].…”

Section: Current Knowledge About the Proteome Of Mtbmentioning

confidence: 99%

Systems proteomics approaches to study bacterial pathogens: application to Mycobacterium tuberculosis

Banaei‐Esfahani

Nicod

Aebersold

et al. 2017

Current Opinion in Microbiology

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Significant developments and improvements in basic and clinical research notwithstanding, infectious diseases still claim at least 13 million lives annually. Classical research approaches have deciphered many molecular mechanisms underlying infection. Today it is increasingly recognized that multiple molecular mechanisms cooperate to constitute a complex system that is used by a given pathogen to interfere with the biochemical processes of the host. Therefore, systems-level approaches now complement the standard molecular biology techniques to investigate pathogens and their interactions with the human host. Here we review omic studies in Mycobacterium tuberculosis, the causative agent of tuberculosis, with a particular focus on proteomic methods and their application to the bacilli. Likewise, the discussed methods are directly portable to other bacterial pathogens.

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Section: Current Knowledge About the Proteome Of Mtbmentioning

confidence: 99%

Systems proteomics approaches to study bacterial pathogens: application to Mycobacterium tuberculosis

Banaei‐Esfahani

Nicod

Aebersold

et al. 2017

Current Opinion in Microbiology

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“…original strain has been modified giving rise to a series of heterogeneous strains, which show clear variations in their genomes and protective immune properties (Castillo-Rodal et al, 2006;Abdallah et al, 2015). With regards to the BCG-Phipps the main regions of differentiation (RD) lost are RD1, RD2 and nRD18.…”

Section: Cows Numbermentioning

confidence: 99%

Effect of a low dose of BCG-Phipps vaccine on the development of reactivity to tuberculin skin test in neonatal calves and adult cows

Corona-GÃ3mez¹,

Jaramillo-Meza²,

PÃ©rez-GonzÃ¡lez³

et al. 2017

J. Vet. Med. Anim. Health

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Bovine tuberculosis (bTB) has a direct impact in the productive and reproductive efficiency of dairy cattle. Nowadays, disease control programs based on tuberculin testing and removal of infected cattle are unaffordable for the developing countries, since there is no program of financial compensation, especially in high bTB-prevalence herds. Thus, control strategies based on vaccination are considered the best alternative. The aim of this study was to evaluate whether a low dose of BCG-Phipps vaccine induces reactivity to tuberculin skin test and its duration in neonatal calves and adult cows. For the analysis of the former, 69 TB-free Holstein-Friesian calves less than one-month old were used; of which, 54 calves were subcutaneously inoculated with 10 4 CFU of the BCG-Phipps vaccine, while the rest remained without vaccination. Under similar conditions of immunization, 133 single intradermal comparative cervical (SICCT) reactors and 133 non-reactors Holstein-Friesian cows of different age were also analyzed. In calves, the SICCT-reactivity was evaluated periodically in the first 14 months post-vaccination (mpv) while, in adult cows, the effect of vaccination on the test was evaluated at six months post-vaccination. A comparative ELISA was used by measuring the antibody levels in the groups. In calves, reactivity frequencies of 7.4 and 3.7% at 3 and 5 mpv, respectively were recorded. This reactivity disappeared at six months. None calves in the control group were reactor during the study. There were no variations in the degree of reactivity in the group adult reactor cows. However, in the non-reactor group, a conversion of 12.8% at six mpv was recorded. In addition, the conversion percentage was higher in older cows than in younger cows (p<0.05). The specific antibody levels did not increase in the vaccinated groups. Data indicate that the low dose of BCG-Phipps vaccine used had a reduced effect on the development of a delayed type hypersensitivity to tuberculin in neonatal calves, and heifers lesser than one-year-old.

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“…Complete genome elucidation of BCG strains is challenging by the occurrence of large genome segment duplications and a high GC content. Therefore, no fully assembled reference genome is yet available for BCG Danish, only incomplete ones 7, 8 , which hinders further standardization efforts.…”

mentioning

confidence: 99%

“…Genetic features determinative for BCG Danish, as described by Abdallah et al . 8 , were identified, including the region of difference (RD) Denmark/Glaxo and the DU2 type III, that was completely resolved in the assembly (Fig. 1a-b).…”

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Reference genome for the WHO reference strain for Mycobacterium bovis BCG Danish, the present tuberculosis vaccine

Borgers

Zheng

et al. 2019

Preprint

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12Mycobacterium bovis bacillus Calmette-Guérin (M. bovis BCG) is the only vaccine available against 13 tuberculosis (TB). This study reports on an integrated genome analysis workflow for BCG, resulting in the 14 completely assembled genome sequence of BCG Danish 1331 (07/270), one of the WHO reference strains 15 for BCG vaccines. We demonstrate how this analysis workflow enables the resolution of genome 16 duplications and of the genome of engineered derivatives of this vaccine strain. 17 MAIN TEXT 18The BCG live attenuated TB vaccine is one of the oldest and most widely used vaccines in human medicine. 19Each year, BCG vaccines are administered to over 100 million newborns (i.e. 75% of all newborns on the 20 planet). The original BCG strain was developed in 1921 at the Pasteur Institute, through attenuation of the 21 bovine TB pathogen M. bovis, by 231 serial passages on potato slices soaked in glycerol-ox bile over a time-22 span of 13 years 1 . This BCG Pasteur strain was subsequently distributed to laboratories around the world 23 and different laboratories maintained their own daughter strains by passaging. Over the years, different 24 substrains arose with different protective efficacy 2,3 . The establishment of a frozen seed-lot system in 1956 25 and the WHO recommendation of 1966 that vaccines should not be prepared from cultures that had 26 undergone >12 passages starting from a defined freeze-dried seed lot, halted the accumulation of 27 additional genetic changes 1 . In an effort to further standardize the vaccine production and to prevent 28 severe adverse reactions related to BCG vaccination, three substrains, i.e. Danish 1331, Tokyo 172-1 and 29Russian BCG-1 were established as the WHO reference strains in 2009 and 2010 4 . Of these, the BCG Danish 30 1331 strain is the most frequently used one, and it also serves as a basis of most current "next-generation" 31 engineering efforts to improve the BCG vaccine or to use it as a "carrier" for antigens of other pathogens 5,6 . 32Complete genome elucidation of BCG strains is challenging by the occurrence of large genome segment 33 2 duplications and a high GC content. Therefore, no fully assembled reference genome is yet available for 34 BCG Danish, only incomplete ones 7,8 , which hinders further standardization efforts. 35By combining second (Illumina) and third (PacBio) generation sequencing technologies and an integrated 36 bioinformatics workflow we have for the first time fully assembled the BCG Danish 1331 (07/270) strain 37 genome sequence. Ambiguous regions were locally reassembled and/or experimentally verified. The single 38 circular chromosome is 4,411,814 bp in length and encodes 4,084 genes, including 4,004 genes encoding 39 for proteins, 5 genes for rRNA, 45 genes for tRNA and 30 pseudogenes (Fig. 1a). Compared to the reference 40 genome sequence of BCG Pasteur 1173P2, 42 SNPs were identified and a selected subset was validated 41 Table 1 and 5). Genetic features determinative for BCG Danish, as described by Abdallah et al. 8 , 42 were ...

show abstract

Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations

Cited by 86 publications

References 88 publications

Systems proteomics approaches to study bacterial pathogens: application to Mycobacterium tuberculosis

Systems proteomics approaches to study bacterial pathogens: application to Mycobacterium tuberculosis

Effect of a low dose of BCG-Phipps vaccine on the development of reactivity to tuberculin skin test in neonatal calves and adult cows

Reference genome for the WHO reference strain for Mycobacterium bovis BCG Danish, the present tuberculosis vaccine

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