Global Assessment of Mycobacterium avium subsp.
            <i>hominissuis</i>
            Genetic Requirement for Growth and Virulence

Dragset, Marte Singsås; Ioerger, Thomas R.; Loevenich, Maja; Haug, Markus; Sivakumar, Niruja; Marstad, Anne; Cardona, Père-Joan; Klinkenberg, Geir; Rubín, Eric J.; Steigedal, Magnus; Flo, Trude Helen

doi:10.1128/msystems.00402-19

Cited by 24 publications

(32 citation statements)

References 77 publications

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“…Overall, even the most divergent of Map strains had a SNP density of only 0.284 SNPs per 1 kb. This compared to 10 SNPs per 1 kb between Mah 104 and MAH11 (Dragset et al, 2019). This analysis confirms that single nucleotide variants are more abundant in Mah than other M. avium subspecies (Uchiya et al, 2017).…”

Section: Snps Among M Avium Subspeciessupporting

confidence: 70%

“…To be included in this study, all genome assemblies had to be complete, closed, and annotated using PGAP with a RefSeq accession number. These criteria excluded one complete genome, the Mah strain MAH11, which did not have a RefSeq accession when this study was conceived and has recently been published (Dragset et al, 2019). Therefore, a total of 13 Map genomes and 15 non-Map RefSeq genomes were analyzed (Tables 1, 2).…”

Section: Refseq Genomes Using Pgap Annotation Reveals Additional Genesmentioning

confidence: 99%

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Genetic Diversity Among Mycobacterium avium Subspecies Revealed by Analysis of Complete Genome Sequences

et al. 2020

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Section: Snps Among M Avium Subspeciessupporting

confidence: 70%

Section: Refseq Genomes Using Pgap Annotation Reveals Additional Genesmentioning

confidence: 99%

Genetic Diversity Among Mycobacterium avium Subspecies Revealed by Analysis of Complete Genome Sequences

et al. 2020

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“…A recent study has sequenced a highly transformable virulent MAH approving novel genes that are essential for infection establishment; from these genes some involve in the growth and others in the virulence of the bacteria (39). katG and pfkA were of these genes that encodes for catalase peroxidase and phosphofructokinase; respectively which were down-and up-regulated in the stationary phase in our proteomic analysis; respectively.…”

Section: Discussionmentioning

confidence: 92%

Differential Protein Expression in Exponential and Stationary Growth Phases of Mycobacterium avium subsp. hominissuis 104

Enany

Ato

Matsumoto

2020

Preprint

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Background:Mycobacterium avium complex (MAC) is the most common non-tuberculous mycobacteria (NTM) causing different types of pulmonary diseases. Although, genomic and transcriptomic analysis of Mycobacterium avium 104 (M. avium 104) have extensively done, little is known about the proteomics of M. avium 104. Methods:We utilized the proteomics technology to analyze the changes in the whole proteome of M. avium 104 during exponential and stationary growth phases. Results:We found 12 dys-regulated proteins; the up-regulated protein hits in the stationary phase were involved in aminopeptidase, choline dehydrogenase, oxidoreductase, and ATP binding, while, the down-regulated proteins in the stationary phase were acetyl-CoA acetyltransferase, universal stress protein, catalase peroxidase, and elongation factor (Tu). The differently expressed proteins between exponential and stationary phases were implicated in metabolism and stress response pointing to the functional adaptation of the cells to the environment. Conclusion:Proteomic analysis in different growth phases could participate in understanding the course of infection, the mechanisms of virulence, the means of survival, and the possible targets for treatment.

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“…During the review of this manuscript, a study by Dragset et al 25 was published describing, in part, the characterization of essential genes of a different strain of MAH using transposon mutagenesis. Interestingly, they observed transposon insertions in 36813 of 55516 TA sites on the chromosome (66.3%) whereas we observed insertions in 47790 of 57588 TA sites (83%).…”

Section: Discussionmentioning

confidence: 99%

“…The higher fraction of occupied TA sites in our study also may reflect our use of a more permissive growth medium (7H11 vs 7H10 agar). Finally, the two studies also utilized different strains of MAH (MAC109 vs MAH 11), which we expect to be a minor factor given their close genetic similarity 25 .…”

Section: Discussionmentioning

confidence: 99%

Identifying the essential genes of Mycobacterium avium subsp. hominissuis with Tn-Seq using a rank-based filter procedure

Matern

Jenquin

Bader

et al. 2020

Sci Rep

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Mycobacterium avium subsp. hominissuis (MAH) is increasingly recognized as a significant cause of morbidity, particularly in elderly patients or those with immune deficiency or underlying lung impairment. Disease due to MAH is particularly difficult to treat, often requiring years of antibiotic therapy. Identification of genes essential for MAH growth may lead to novel strategies for improving curative therapy. Here we have generated saturating genome-wide transposon mutant pools in a strain of MAH (MAC109) and developed a novel computational technique for classifying annotated genomic features based on the in vitro effect of transposon mutagenesis. Our findings may help guide future genetic and biochemical studies of MAH pathogenesis and aid in the identification of new drugs to improve the treatment of these serious infections. The genus Mycobacterium contains a variety of difficult-to-treat pathogens frequently associated with pulmonary disease. One of these pathogens, Mycobacterium avium subsp. hominissuis (MAH), is an opportunistic pathogen associated with significant morbidity in the elderly and in patients with underlying lung disease 1,2 , as well as increased mortality in patients with AIDS 3. Similar to other mycobacteria, MAH is often difficult to treat effectively with existing antibiotic combinations. Current antibiotic regimens require a median of 5 months to convert the sputum to a culture-negative state 4 , with current guidelines recommending treatment for at least 1 year after sputum culture conversion 5. Furthermore, a large fraction of patients fail to convert after 1 year of therapy 4. Patients could greatly benefit from more potent and abbreviated therapies. Transposon sequencing (e.g., TraDIS 6 , Tn-Seq. 7 , INseq. 8) has been used extensively to profile haploid genomes and identify gene disruptions that affect bacterial growth under various conditions. Of potential interest in drug development are those drug targets which profoundly disrupt growth on nutrient-rich media (i.e., "essential" genes). In the current study, we have successfully generated genome-wide transposon mutant pools in MAH strain 109 (MAC109). This strain, which was originally isolated from the blood of an AIDS patient, has been characterized extensively in previous studies 9-13 and is known to infect mice and macrophages 11. We have utilized the transposon mutant pools we generated to identify genes critical for MAH growth in vitro with the goal of informing future research in MAH pathogenesis and drug development. In order to make gene essentiality predictions, we developed a new statistical approach for calling genes based on ranking the read counts from each mutant and applied this to new Tn-Seq data. We report our predictions of the essential genes of MAH and compare these with the predicted set of essential genes in the closely related human pathogen, Mycobacterium tuberculosis (Mtb). Results Constructing genome-wide transposon mutant pools in Mycobacterium avium subsp. hominissuis. To identify a suitable strain of ...

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Global Assessment of Mycobacterium avium subsp. hominissuis Genetic Requirement for Growth and Virulence

Cited by 24 publications

References 77 publications

Genetic Diversity Among Mycobacterium avium Subspecies Revealed by Analysis of Complete Genome Sequences

Genetic Diversity Among Mycobacterium avium Subspecies Revealed by Analysis of Complete Genome Sequences

Differential Protein Expression in Exponential and Stationary Growth Phases of Mycobacterium avium subsp. hominissuis 104

Identifying the essential genes of Mycobacterium avium subsp. hominissuis with Tn-Seq using a rank-based filter procedure

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