Dataset Information

NAD+ auxotrophy is bacteriocidal for the tubercle bacilli.

ABSTRACT: The human tubercle bacillus Mycobacterium tuberculosis can synthesize NAD(+) using the de novo biosynthesis pathway or the salvage pathway. The salvage pathway of the bovine tubercle bacillus Mycobacterium bovis was reported defective due to a mutation in the nicotinamidase PncA. This defect prevents nicotinic acid secretion, which is the basis for the niacin test that clinically distinguishes M. bovis from M. tuberculosis. Surprisingly, we found that the NAD(+)de novo biosynthesis pathway (nadABC) can be deleted from M. bovis, demonstrating a functioning salvage pathway. M. bovisDeltanadABC fails to grow in mice, whereas M. tuberculosisDeltanadABC grows normally in mice, suggesting that M. tuberculosis can acquire nicotinamide from its host. The introduction of M. tuberculosis pncA into M. bovisDeltanadABC is sufficient to fully restore growth in a mouse, proving that the functional salvage pathway enables nicotinamide acquisition by the tubercle bacilli. This study demonstrates that NAD(+) starvation is a cidal event in the tubercle bacilli and confirms that enzymes common to the de novo and salvage pathways may be good drug targets.

SUBMITTER: Vilcheze C

PROVIDER: S-EPMC2945688 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

NAD+ auxotrophy is bacteriocidal for the tubercle bacilli.

Vilchèze Catherine C Weinrick Brian B Wong Ka-Wing KW Chen Bing B Jacobs William R WR

Molecular microbiology 20100228 2

The human tubercle bacillus Mycobacterium tuberculosis can synthesize NAD(+) using the de novo biosynthesis pathway or the salvage pathway. The salvage pathway of the bovine tubercle bacillus Mycobacterium bovis was reported defective due to a mutation in the nicotinamidase PncA. This defect prevents nicotinic acid secretion, which is the basis for the niacin test that clinically distinguishes M. bovis from M. tuberculosis. Surprisingly, we found that the NAD(+)de novo biosynthesis pathway (nadA ...[more]

PMID: 20199601

Similar Datasets

Project description:Eusocial bees (such as honey bees and bumble bees) harbor core gut microbiomes that are transmitted through social interaction between nestmates. Carpenter bees are not eusocial; however, recent microbiome analyses found that Xylocopa species harbor distinctive core gut microbiomes. In this study, we analyzed the gut microbiomes of three Xylocopa species in Japan between 2016 and 2021 by V1 to V2 region-based 16S rDNA amplicon sequencing, and 14 candidate novel species were detected based on the full-length 16S rRNA gene sequences. All Xylocopa species harbor core gut microbiomes consisting of primarily lactic acid bacteria (LAB) that were phylogenetically distant from known species. Although they were difficult to cultivate, two LAB species from two different Xylocopa species were isolated by supplementing bacterial culture supernatants. Both genomes exhibited an average LAB genome size with a large set of genes for carbohydrate utilization but lacked genes to synthesize an essential coenzyme NAD, which is unique among known insect symbionts. Our findings of phylogenetically distinct core LAB of NAD auxotrophy reflected the evolution of Xylocopa-restricted bacteria retention and maintenance through vertical transmission of microbes during solitary life. We propose five candidate novel species belonging to the families Lactobacillaceae and Bifidobacteriaceae, including a novel genus, and their potential functions in carbohydrate utilization. IMPORTANCE Recent investigations found unique microbiomes in carpenter bees, but the description of individual microbes, including isolation and genomics, remains largely unknown. Here, we found that the Japanese Xylocopa species also harbor core gut microbiomes. Although most of them were difficult to isolate a pure colony, we successfully isolated several strains. We performed whole-genome sequencing of the isolated candidate novel species and found that the two Lactobacillaceae strains belonging to the Xylocopa-specific novel LAB clade lack the genes for synthesizing NAD, a coenzyme central to metabolism in all living organisms. Here, we propose a novel genus for the two LAB species based on very low 16S rRNA gene sequence similarities and genotypic characters.

Dataset Information

NAD+ auxotrophy is bacteriocidal for the tubercle bacilli.

Publications

NAD+ auxotrophy is bacteriocidal for the tubercle bacilli.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets