Complete Genome Sequence, Genome Stability and Phylogeny of the Vaccine Strain Mycobacterium bovis BCG SL222 Sofia

Mycobacterium bovis bacillus Calmette–Guérin (BCG) is the only live attenuated vaccine available against tuberculosis. The first BCG vaccination was done exactly 100 years ago, in 1921. The BCG vaccine strains used worldwide represent a family of daughter sub-strains with distinct genotypic characteristics. BCG SL222 Sofia is a seed lot sub-strain descending from the Russian BCG-I (seed lot 374a) strain and has been used for vaccine production in Bulgaria since 1972. Here, we report the assembled circular genome sequence of Mycobacterium bovis BCG SL222 Sofia and phylogeny analysis with the most closely related BCG sub-strains. The full circular genome of BCG SL222 Sofia had a length of 4,370,706 bp with an average GC content of 65.60%. After 49 years of in vitro evolution in a freeze-dried condition, we identified four SNP mutations as compared to the reference BCG-I (Russia-368) sequence. BCG vaccination is of central importance for the TB elimination programs in many countries. Since 1991, almost 40 million vaccine doses of the BCG SL222 Sofia have been distributed annually through the United Nations Children’s Fund (UNICEF) and the Pan American Health Organization (PAHO) to approximately 120 countries. The availability of the complete reference genome sequence for M. bovis BCG SL222 Sofia, a WHO reference reagent for the Russian BCG-I sub-strain, will facilitate the identity assurance of the genomic stability, will contribute to more consistent manufacturing, and has an important value in standardization and differentiation of sub-strains used in vaccine production. We propose to rename the sub-strain BCG SL222 Sofia to BCG-Sofia for practical and common use.

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Complete Genome Sequence of Mycobacterium bovis BCG SL222 Sofia, the First WHO Reference Reagent for the M. bovis BCG Vaccine of the Russian BCG-I Substrain

Microbiology Resource Announcements ◽

10.1128/mra.01318-20 ◽

2021 ◽

Vol 10 (3) ◽

Author(s):

Stefan Panaiotov ◽

Yordan Hodzhev ◽

Vladimir Tolchkov ◽

Alexander Mihailov ◽

Roumen Kofinov ◽

...

Keyword(s):

Mycobacterium Bovis ◽

Vaccine Strain ◽

Genome Sequence ◽

Complete Genome Sequence ◽

Complete Genome ◽

Bcg Vaccine ◽

Vaccine Production ◽

Content Type ◽

Mycobacterium Bovis Bcg

ABSTRACT Mycobacterium bovis BCG SL222 Sofia is a substrain descending from the Russian BCG-I vaccine strain. Here, we report the complete genome sequence of BCG SL222 Sofia, which will facilitate identity assurance and will contribute to more consistent manufacturing, standardization, and differentiation of substrains used in vaccine production.

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Polyfunctional CD4 T-cells correlate with in vitro mycobacterial growth inhibition following Mycobacterium bovis BCG-vaccination of infants

Vaccine ◽

10.1016/j.vaccine.2016.09.002 ◽

2016 ◽

Vol 34 (44) ◽

pp. 5298-5305 ◽

Cited By ~ 28

Author(s):

Steven G. Smith ◽

Andrea Zelmer ◽

Rose Blitz ◽

Helen A. Fletcher ◽

Hazel M. Dockrell

Keyword(s):

T Cells ◽

Growth Inhibition ◽

Mycobacterium Bovis ◽

Cd4 T Cells ◽

Mycobacterium Bovis Bcg ◽

Bcg Vaccination ◽

Mycobacterial Growth

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Survival of Mycobacterium bovis BCG oral vaccine during transit through a dynamic in vitro model simulating the upper gastrointestinal tract of badgers

PLoS ONE ◽

10.1371/journal.pone.0214859 ◽

2019 ◽

Vol 14 (4) ◽

pp. e0214859 ◽

Cited By ~ 1

Author(s):

Gareth A. Williams ◽

Marjorie E. Koenen ◽

Robert Havenaar ◽

Paul Wheeler ◽

Sonya Gowtage ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Mycobacterium Bovis ◽

In Vitro Model ◽

Oral Vaccine ◽

Upper Gastrointestinal Tract ◽

Mycobacterium Bovis Bcg ◽

Vitro Model ◽

Upper Gastrointestinal

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Complete Genome Sequence of a Gram-Positive Bacterium, Leifsonia sp. Strain PS1209, a Potato Endophyte

Microbiology Resource Announcements ◽

10.1128/mra.00447-20 ◽

2020 ◽

Vol 9 (26) ◽

Author(s):

Yingyu Liu ◽

Xing Ma ◽

Tyler C. Helmann ◽

Heather McLane ◽

Paul Stodghill ◽

...

Keyword(s):

Genome Sequence ◽

Complete Genome Sequence ◽

Complete Genome ◽

Gc Content ◽

Potato Cultivar ◽

Positive Bacterium ◽

Gram Positive ◽

Circular Genome ◽

Apparently Healthy

ABSTRACT We report the complete and annotated genome sequence of a Gram-positive bacterium, Leifsonia sp. strain PS1209, a potato endophyte that was isolated from apparently healthy tubers of potato cultivar NY166. The circular genome is 4,091,164 bp long, with a GC content of 69.08%, containing 3,926 genes.

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Development of an in vitro model of the early-stage bovine tuberculous granuloma using Mycobacterium bovis-BCG

Veterinary Immunology and Immunopathology ◽

10.1016/j.vetimm.2015.10.005 ◽

2015 ◽

Vol 168 (3-4) ◽

pp. 249-257 ◽

Cited By ~ 2

Author(s):

Laura Garza-Cuartero ◽

Elaine McCarthy ◽

Joseph Brady ◽

Joseph Cassidy ◽

Clare Hamilton ◽

...

Keyword(s):

Mycobacterium Bovis ◽

In Vitro Model ◽

Early Stage ◽

Mycobacterium Bovis Bcg ◽

Tuberculous Granuloma ◽

Vitro Model

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Analysis of the Genome Sequence of Lactobacillus gasseri ATCC 33323 Reveals the Molecular Basis of an Autochthonous Intestinal Organism

Applied and Environmental Microbiology ◽

10.1128/aem.00054-08 ◽

2008 ◽

Vol 74 (15) ◽

pp. 4610-4625 ◽

Cited By ~ 113

Author(s):

M. Andrea Azcarate-Peril ◽

Eric Altermann ◽

Yong Jun Goh ◽

Richard Tallon ◽

Rosemary B. Sanozky-Dawes ◽

...

Keyword(s):

Genome Sequence ◽

Native Species ◽

Bacterial Species ◽

Gc Content ◽

Intestinal Epithelial ◽

Growth And Survival ◽

Lactobacillus Gasseri ◽

Bacteriophage Infection ◽

A Genome

ABSTRACT This study presents the complete genome sequence of Lactobacillus gasseri ATCC 33323, a neotype strain of human origin and a native species found commonly in the gastrointestinal tracts of neonates and adults. The plasmid-free genome was 1,894,360 bp in size and predicted to encode 1,810 genes. The GC content was 35.3%, similar to the GC content of its closest relatives, L. johnsonii NCC 533 (34%) and L. acidophilus NCFM (34%). Two identical copies of the prophage LgaI (40,086 bp), of the Sfi11-like Siphoviridae phage family, were integrated tandomly in the chromosome. A number of unique features were identified in the genome of L. gasseri that were likely acquired by horizontal gene transfer and may contribute to the survival of this bacterium in its ecological niche. L. gasseri encodes two restriction and modification systems, which may limit bacteriophage infection. L. gasseri also encodes an operon for production of heteropolysaccharides of high complexity. A unique alternative sigma factor was present similar to that of B. caccae ATCC 43185, a bacterial species isolated from human feces. In addition, L. gasseri encoded the highest number of putative mucus-binding proteins (14) among lactobacilli sequenced to date. Selected phenotypic characteristics that were compared between ATCC 33323 and other human L. gasseri strains included carbohydrate fermentation patterns, growth and survival in bile, oxalate degradation, and adhesion to intestinal epithelial cells, in vitro. The results from this study indicated high intraspecies variability from a genome encoding traits important for survival and retention in the gastrointestinal tract.

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Extended freeze-dried Mycobacterium bovis Bacillus Calmette-Guérin induces the release of interleukin-12 but not tumour necrosis factor-α by alveolar macrophages, both in vitro and in vivo

Clinical & Experimental Allergy ◽

10.1046/j.1365-2222.2003.01612.x ◽

2003 ◽

Vol 33 (3) ◽

pp. 386-393 ◽

Cited By ~ 15

Author(s):

C. Hubeau ◽

M. Singer ◽

M. Lagranderie ◽

G. Marchal ◽

B. Vargaftig

Keyword(s):

Mycobacterium Bovis ◽

Tumour Necrosis ◽

Interleukin 12 ◽

Bacillus Calmette Guerin ◽

Tumour Necrosis Factor Α ◽

Freeze Dried ◽

Factor Α ◽

Necrosis Factor

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Environmental Strains of Mycobacterium avium Interfere with Immune Responses Associated with Mycobacterium bovis BCG Vaccination

Infection and Immunity ◽

10.1128/iai.01826-06 ◽

2007 ◽

Vol 75 (6) ◽

pp. 2833-2840 ◽

Cited By ~ 34

Author(s):

Sarah L. Young ◽

Lynn Slobbe ◽

Rachel Wilson ◽

Bryce M. Buddle ◽

Geofferey W. de Lisle ◽

...

Keyword(s):

Immune System ◽

Mycobacterium Bovis ◽

Mycobacterium Avium ◽

Growth Characteristics ◽

Mycobacterial Antigen ◽

Serological Response ◽

Necrosis Factor Alpha ◽

Activation Markers ◽

Bcg Vaccination

ABSTRACT Prior exposure of a vaccinee to certain species of environmental mycobacteria can prime the immune system against common mycobacterial antigens, which can in turn reduce the subsequent efficacy of live attenuated mycobacterial vaccines (such as Mycobacterium bovis BCG), in both human and livestock vaccination programs. In this study, two strains of Mycobacterium avium, both isolated from New Zealand livestock, were investigated to determine their growth characteristics and effects on the immune system in murine models. Markedly different effects on the immune system were observed; an IS901-negative strain (WAg 207) induced significant up-regulation of cell surface activation markers (major histocompatibility complex II, CD80, and CD86) on in vitro-derived dendritic cells and induced the release of proinflammatory monokines (interleukin-1β [IL-1β], IL-6, and tumor necrosis factor alpha) in dendritic cell-macrophage cocultures following direct in vitro contact of cells with bacteria. In contrast, an IS901-positive strain (WAg 206) had none of these effects. When mice were exposed to M. avium via oral infection prior to BCG parenteral immunization, both strains were shown to be capable of decreasing subsequent antigen-stimulated gamma interferon secretion by splenic lymphocytes, although this effect was more significant for strain WAg 206. Both strains also induced a mycobacterial antigen-specific serological response in M. avium-sensitized and BCG-immunized mice; this response was greater in WAg 206-sensitized mice, and there was a predominance of immunoglobulin G1 antibody. The down-regulation of IFN-γ responses and the up-regulation of antibody responses are characteristic of a switch to a type 2 immune response. The different results may be linked to the inherent growth characteristics of the two strains, since WAg 206 was shown to grow slowly in murine macrophages in vitro and to cause a persistent systemic infection following infection in vivo, while WAg 207 grew fast and did not persist in mice. The implications of these findings for BCG vaccination protocols are discussed.

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