Molecular Cloning and Functional Analysis of a Novel Tetracycline Resistance Determinant,
 tet
 (V), from
 Mycobacterium smegmatis

Rossi, Edda De; Blokpoel, Marian C. J.; Cantoni, Rita; Branzoni, Manuela; Riccardi, Giovanna; Young, Douglas; Smet, K. A. L. De; Ciferri, Orio

doi:10.1128/aac.42.8.1931

Cited by 61 publications

(35 citation statements)

References 52 publications

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“…The gene tet (V) encoding a tetracycline efflux pump (19) was found in 73% soil isolates and 37% clinical isolates, including species where it has not been reported previously, i.e. , M. septicum , M. litorale , M. alvei , M. peregrinum , M. goodii , M. arupense and M. neoaurum .…”

Section: Discussionmentioning

confidence: 93%

Tetracycline Resistance and Presence of Tetracycline Resistance Determinants tet(V) and tap in Rapidly Growing Mycobacteria from Agricultural Soils and Clinical Isolates

et al. 2012

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Rapidly growing mycobacteria (RGM) inhabit soil and water but certain strains represent a health risk for human and animals. Both clinical and soil RGM may be under selection pressure for resistance to tetracycline (TET) antibiotics, since tetracyclines are administrated to humans and farm animals, and TET residues enter soil through manuring; however, resistance to TET and the presence of TET-resistance genes have been assessed only in clinical isolates. We were therefore interested in comparing soil and clinical RGM in terms of TET resistance and the presence of TET-resistance genes. We used 44 RGM from grasslands with different exposure to animal manure, and 38 clinical RGM from Czech hospitals. There was no difference between the clinical and soil isolates in TET resistance, with >50% resistant isolates in both groups. otr(A), otr(B), tet(K), tet(L) or tet(M) were not detected in any soil or clinical isolate. In contrast, most isolates harbored tet(V) and tap, both encoding mycobacterial efflux pumps, including species where these genes have never been evidenced before. The phylogeny of tet(V) correlated with isolates’ BOX-PCR profiles, suggesting that this gene evolved along with mycobacterial genomes as a part of the intrinsic resistome. In certain cases, tet(V) and/or tap were found in TET-sensitive isolates, or inversely, were not found in resistant strains. Concluding, intrinsic efflux pumps may be more important for TET resistance than horizontally transferred genes in both soil and clinical RGM. Their simple presence, however, does not attest to resistance, and therefore their diversity, function and expression merit further research.

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Section: Discussionmentioning

confidence: 93%

Tetracycline Resistance and Presence of Tetracycline Resistance Determinants tet(V) and tap in Rapidly Growing Mycobacteria from Agricultural Soils and Clinical Isolates

et al. 2012

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“…28 Overexpression of tet(V) , which has been previously characterized as a tetracycline efflux membrane transport protein, conferred an 8-fold increase in MIC to SKI-356313 (Figure 4C). 29 …”

Section: Results and Discussionmentioning

confidence: 99%

Novel Imidazoline Antimicrobial Scaffold That Inhibits DNA Replication with Activity against Mycobacteria and Drug Resistant Gram-Positive Cocci

Harris

Fay²,

Yan³

et al. 2014

ACS Chem. Biol.

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Bacterial antimicrobial resistance is an escalating public health threat, yet the current antimicrobial pipeline remains alarmingly depleted, making the development of new antimicrobials an urgent need. Here, we identify a novel, potent, imidazoline antimicrobial compound, SKI-356313, with bactericidal activity against Mycobacterium tuberculosis and Gram-positive cocci, including vancomycin-resistant Enterococcus faecium (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). SKI-356313 is active in murine models of Streptococcus pneumoniae and MRSA infection and is potently bactericidal for both replicating and nonreplicating M. tuberculosis. Using a combination of genetics, whole genome sequencing, and a novel target ID approach using real time imaging of core macromolecular biosynthesis, we show that SKI-356313 inhibits DNA replication and displaces the replisome from the bacterial nucleoid. These results identify a new antimicrobial scaffold with a novel mechanism of action and potential therapeutic utility against nonreplicating M. tuberculosis and antibiotic resistant Gram-positive cocci.

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“…The first mycobacterial macrolide resistance gene to be reported was mmr (also called emrE = Rv3065 [6]) belonging to the SMR family of multidrug efflux proteins. This M. tuberculosis gene confers resistance to several drugs, including erythromycin, when expressed on a multicopy vector in M. smegmatis [112]. [112], in M. avium and also in M. smegmatis, although with a weaker similarity.…”

Section: Macrolide Resistance Determinants In Mycobacteriamentioning

confidence: 98%

“…This M. tuberculosis gene confers resistance to several drugs, including erythromycin, when expressed on a multicopy vector in M. smegmatis [112]. [112], in M. avium and also in M. smegmatis, although with a weaker similarity. Nothing is known about the expression of mmr or its homologues, but their presence in macrolide sensitive strains is not in favor of a determinant role of these genes in macrolide resistance.…”

Section: Macrolide Resistance Determinants In Mycobacteriamentioning

confidence: 98%

Macrolide Resistance in Mycobacteria

Doucet‐Populaire¹,

Buriánková²,

Weiser³

et al. 2005

MCRO

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The genus Mycobacterium contains two of the most important human pathogens, Mycobacterium tuberculosis and Mycobacterium leprae, the etiological agents of tuberculosis and leprosy, respectively. Other mycobacteria are mostly saprophytic organisms, living in soil and water, but some of them can cause opportunistic infections. The increasing incidence of tuberculosis as well as infections with non-tuberculous mycobacteria (NTM) in immuno-compromised patients has renewed interest in molecular mechanisms of drug resistance in these pathogens. Mycobacteria show a high degree of intrinsic resistance to most common antibiotics. For instance, species from the M. tuberculosis complex (MTC) are intrinsically resistant to macrolides. Nevertheless, some semi-synthetic macrolides as clarithromycin, azithromycin and most recently the ketolides, are active against NTM and widely used for infection treatment. However, shortly after the introduction of these new drugs, resistant strains appeared due to mutations affecting the macrolide target, the ribosome. The mycobacterial cell wall is considered to be a major factor in promoting the natural resistance of mycobacteria to various antibiotics. However, recent data show that specific macrolide resistance determinants (erm genes) are present in some species.This mini-review summarizes the current knowledge on the natural and acquired macrolide resistance in mycobacteria, gives an overview of potential mechanisms implicated in the intrinsic resistance and of macrolide resistance determinants in mycobacteria.

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Molecular Cloning and Functional Analysis of a Novel Tetracycline Resistance Determinant, tet (V), from Mycobacterium smegmatis

Cited by 61 publications

References 52 publications

Tetracycline Resistance and Presence of Tetracycline Resistance Determinants <i>tet</i>(V) and <i>tap</i> in Rapidly Growing Mycobacteria from Agricultural Soils and Clinical Isolates

Tetracycline Resistance and Presence of Tetracycline Resistance Determinants <i>tet</i>(V) and <i>tap</i> in Rapidly Growing Mycobacteria from Agricultural Soils and Clinical Isolates

Novel Imidazoline Antimicrobial Scaffold That Inhibits DNA Replication with Activity against Mycobacteria and Drug Resistant Gram-Positive Cocci

Macrolide Resistance in Mycobacteria

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