Cell Wall-Affecting Antibiotics Induce Expression of a Novel Gene, drp35, in Staphylococcus aureus

Murakami, Hiroyuki; Matsumaru, Hiroyuki; Kanamori, Mutsumi; Hayashi, Hideo; Ohta, Toshiko

doi:10.1006/bbrc.1999.1388

Cited by 24 publications

(27 citation statements)

References 21 publications

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“…It has been postulated that this pathway acts as an ATP source in small colony variants lacking a functional respiratory chain (10,24), an idea that is supported by the fact that respiration is severely downregulated in uninduced RN4220spacmvaS, RN4220spacmvaA, and RN4220spacmvaK. Finally, further confirming that downregulation of the mevalonate pathway has a significant effect on cell wall biosynthesis, drp35, a stress lactonase shown to be upregulated in response to beta-lactams, bacitracin, vancomycin, and fosfomycin (17,18), was upregulated between 6 and 10-fold in all 3 downregulated mutants (see Table S2 in the supplemental material, p. 5). Mutant specific changes.…”

Section: Resultsmentioning

confidence: 78%

The Mevalonate Pathway ofStaphylococcus aureus

Balibar¹,

Shen²,

Tao³

2009

J Bacteriol

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Isoprenoids are a class of ubiquitous organic molecules synthesized from the five-carbon starter unit isopentenyl pyrophosphate (IPP). Comprising more than 30,000 known natural products, isoprenoids serve various important biological functions in many organisms. In bacteria, undecaprenyl pyrophosphate is absolutely required for the formation of cell wall peptidoglycan and other cell surface structures, while ubiquinones and menaquinones, both containing an essential prenyl moiety, are key electron carriers in respiratory energy generation. There is scant knowledge on the nature and regulation of bacterial isoprenoid pathways. In order to explore the cellular responses to perturbations in the mevalonate pathway, responsible for producing the isoprenoid precursor IPP in many gram-positive bacteria and eukaryotes, we constructed three strains of Staphylococcus aureus in which each of the mevalonate pathway genes is regulated by an IPTG (isopropyl-␤-D-thiogalactopyranoside)-inducible promoter. We used DNA microarrays to profile the transcriptional effects of downregulating the components of the mevalonate pathway in S. aureus and demonstrate that decreased expression of the mevalonate pathway leads to widespread downregulation of primary metabolism genes, an upregulation in virulence factors and cell wall biosynthetic determinants, and surprisingly little compensatory expression in other isoprenoid biosynthetic genes. We subsequently correlate these transcriptional changes with downstream metabolic consequences.

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Section: Resultsmentioning

confidence: 78%

The Mevalonate Pathway ofStaphylococcus aureus

Balibar¹,

Shen²,

Tao³

2009

J Bacteriol

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“…These observations may indicate existence of a novel sub-MIC effect of ␤-lactam antibiotics, inducing activation of cell wall synthesis of S. aureus. It has been demonstrated recently that ␤-lactams can induce expression of certain cell wall synthesis-associated genes, such as pbp2, in S. aureus (17). Recently, we have also found that ␤-lactams induce increased transcription of a response regulator gene, vraR, which is considered to be at least partially responsible for the increased vancomycin resistance in Mu3 (16).…”

mentioning

confidence: 72%

Combination Effect of Vancomycin and β-Lactams against a Staphylococcus aureus Strain, Mu3, with Heterogeneous Resistance to Vancomycin

Aritaka

Hanaki

Cui

et al. 2001

Antimicrob Agents Chemother

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We tested the combined activity of vancomycin and seven ␤-lactam antibiotics against Staphylococcus aureus clinical strain Mu3, which displays heterogeneous resistance to vancomycin. When combined with vancomycin, four of the seven tested ␤-lactams exhibited an additive effect at or near their MICs, while all showed an antagonistic effect at lower, sub-MIC levels. This study implicated the unpredictable nature of combination therapy of ␤-lactams and vancomycin against S. aureus with reduced susceptibility to vancomycin.

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“…Related to the cell envelope, classified under Cellular Processes, are ftsW, divIB, ftsZ, and SA0555 and SA0551, encoding cell division proteins. Also classified in this category are bacA (encoding bacitracin resistance protein) and drp35, previously shown to be inducible by cell wall-active antibiotics (43,66). Another prominent category into which cell wall stress stimulon member genes fall is Protein Fate, which includes chaperones and proteases (31,63).…”

Section: Fig 2 Daptomycin Gics For S Aureus Strains N315 (A) and Kmentioning

confidence: 99%

Transcriptional Profiling Reveals that Daptomycin Induces the Staphylococcus aureus Cell Wall Stress Stimulon and Genes Responsive to Membrane Depolarization

Muthaiyan

Silverman

Jayaswal

et al. 2008

Antimicrob Agents Chemother

193

176

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Cell Wall-Affecting Antibiotics Induce Expression of a Novel Gene, drp35, in Staphylococcus aureus

Cited by 24 publications

References 21 publications

The Mevalonate Pathway ofStaphylococcus aureus

The Mevalonate Pathway ofStaphylococcus aureus

Combination Effect of Vancomycin and β-Lactams against a Staphylococcus aureus Strain, Mu3, with Heterogeneous Resistance to Vancomycin

Transcriptional Profiling Reveals that Daptomycin Induces the Staphylococcus aureus Cell Wall Stress Stimulon and Genes Responsive to Membrane Depolarization

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