Evolution of M. bovis BCG Vaccine: Is Niacin Production Still a Valid Biomarker?

Table 1

Characterization and comparison of different conventional biochemical and molecular tests to identify different Mycobacterium bovis (BCG) and Mycobacterium tuberculosis species.

Tests strain	M. bovis BCG P3	M. tuberculosis H37Rv	Remarks
Nitrate reduction	Negative	Positive	¥
Niacin	Positive	Positive
Catalase	Negative	Negative
hsp65-PCR	Positive	Positive
esat6-PCR	Negative	Positive
Mac-PCR	Negative	Negative
MPT64 antigen	Negative	Positive
MPT63 antigen	Positive	Positive
Binary spoligotyping	■■□■■■■■□■■■■■■□■■■■■■■■■■■■■■■■■■■■■■□□□□□	■■■■■■■■■■■■■■■■■■■□□■■■■■■■■■■■□□□□■■■■■■■
Octal number	676773777777600	777777477760771
Shared type	482	451
Lineage/sublineages	Bovis1_BCG	H37Rv
Guinea pig virulence	Non-virulent	Virulent	Ψ
	M. bovis BCG (Tokyo)	M. tuberculosis H37Ra
Nitrate reduction	Positive	Positive	[14]
Niacin	Positiv	Positive
Catalase	Negative	Positiv
	M. bovis BCG (ATCC 19274), M. bovis BCG (Biken)	M. tuberculosis H37Rv (TMC102), H37Rv (Biken), H37Ra (Biken)
Niacin test	Weakly Positive	Pos	[15]
	BCG Copenhagen, BCG Glaxo, BCG Pasteur, BCG Tice	M. tuberculosis H37Rv, M. tuberculosis H37Ra
MPB64	Negative	Positive	[15]
MPB70	Positive	Positive
16SrRNA	Positive	Positive
	BCG Tokyo, BCG Moreau, BCG Russia, BCG Sweden.  M. bovis AN5	—
MPB64	Positive	—	[16]
MPB70	Positive	—
16SrRNA	Positive	—
	M. bovis BCG (Glaxo, Pasteur, Tice)	M. tuberculosis (H37Rv)
MPB64	Negative	Positive	[16]
IS6110 copy number	1	—
	M. bovis BCG (Brazilian, Japanese, Russian, Swedish)
MPB64	Positive		[16]
IS6110 copy number	2	—
	M. bovis BCG	M. tuberculosis (classical)
Nitrate reduction	Positive	Positive	[17]
Niacin	Negative	Positive
	M. bovis BCG	M. tuberculosis (classical)
Nitrate reduction	Negative	Positive	[18]
Niacin	Negative	Positive
MPB70	Positive	Positive
Mtp40	Negative	Positiv (very occasionally)
	M. bovis BCG	M. tuberculosis
Nitrate reduction	Negative	Positive	[19]
Niacin	Negative	Positive
MPB70	Positive	Negative
Mtp40	Negative	Positive
Spoligotyping spacer 39–43	Negative	Positive
	M. bovis	M. tuberculosis
Nitrate reduction	Negative	Positive	[20]
Niacin accumulation	Negative	Positive
Presence of mtp40	Negative	Positive
Spoligotype; (characteristic features)	At least one of spacers 39–43 present	Spacers 39–43 absent
	M. bovis BCG	M. tuberculosis (H37Rv)
Binary spoligotyping	■■□□□■■■□■■■■■■□■■■■□■■■■■■■■■■■■■■■■■□□□□□	■■■■■■■■■■■■■■■■■■■□□■■■■■■■■■■■□□□□■■■■■■■	[21]
Octal number	616773677777600	777777477760771
Shared type	663	451
	BOVIS1	H37Rv
	M. bovis	M. tuberculosis
Spacers 33 to 36; (derived from BCG)	—	M. tuberculosis does not hybridize to the spacers	[22]
Spacers 39 to 43; (derived from M. tuberculosis)	M. bovis and BCG do not hybridize to the spacers	—
	M. bovis	M. tuberculosis (H37Rv)
Capilia TB-Neo	Positive	Positive	[23]
SD MPT64	Positive	Positive
TbcID	Positive	Positive
	M. bovis BCG Tokyo	M. bovis BCG Connaught
Capilia TB-Neo	Positive	Negative	[23]

Our analysis on the Indian seed-lot; personal communication with the Director of the BCG vaccine producing laboratory; very occasionally positive; Weak Positive.