Transcriptional Signature following Inhibition of Early-Stage Cell Wall Biosynthesis in
            <i>Staphylococcus aureus</i>

O’Neill, Alex J.; Lindsay, Jodi A.; Gould, Katherine A.; Hinds, Jason; Chopra, Ian

doi:10.1128/aac.01309-08

Cited by 12 publications

(14 citation statements)

References 17 publications

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“…Exposure to cell wall-active antibiotics is known to induce cell wall stress controlled by the two-component system VraSR; thereby, transcription of cell wallrelated genes, such as murZ, murI, pbp2, and sgtB, is induced (3,4), and increasing amounts of the proteins Ddl, FemA, Cap5M, and MurZ were confirmed (9,41). Regarding the strongly enhanced MurZ level, an unrestricted flux of PG precursors from UDPGlcNAc-enolpyruvate to UPD-MurNAc-pentapeptide is assumed (41,51), promoting PG biosynthesis to circumvent cell wall damage. In this study, the boosted PG synthesis led to a drastic accumulation of soluble PG precursors that was accompanied by a complete rearrangement of the metabolome.…”

Section: Resultsmentioning

confidence: 99%

Impact of Antibiotics with Various Target Sites on the Metabolome of Staphylococcus aureus

Dörries

Schlueter

Lalk

2014

Antimicrob Agents Chemother

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In this study, global intra-and extracellular metabolic profiles were exploited to investigate the impact of antibiotic compounds with different cellular targets on the metabolome of Staphylococcus aureus HG001. Primary metabolism was largely covered, yet uncommon staphylococcal metabolites were detected in the cytosol of S. aureus, including sedoheptulose-1,7-bisphosphate and the UDP-MurNAc-pentapeptide with an alanine-seryl residue. By comparing the metabolic profiles of unstressed and stressed staphylococcal cells in a time-dependent manner, we found far-ranging effects within the metabolome. For each antibiotic compound, accumulation as well as depletion of metabolites was detected, often comprising whole biosynthetic pathways, such as central carbon and amino acid metabolism and peptidoglycan, purine, and pyrimidine synthesis. Ciprofloxacin altered the pool of (deoxy)nucleotides as well as peptidoglycan precursors, thus linking stalled DNA and cell wall synthesis. Erythromycin tended to increase the amounts of intermediates of the pentose phosphate pathway and lysine. Fosfomycin inhibited the first enzymatic step of peptidoglycan synthesis, which was followed by decreased levels of peptidoglycan precursors but enhanced levels of substrates such as UDP-GlcNAc and alanine-alanine. In contrast, vancomycin and ampicillin inhibited the last stage of peptidoglycan construction on the outer cell surface. As a result, the amounts of UDP-MurNAc-peptides drastically increased, resulting in morphological alterations in the septal region and in an overall decrease in central metabolite levels. Moreover, each antibiotic affected intracellular levels of tricarboxylic acid cycle intermediates.

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Section: Resultsmentioning

confidence: 99%

Impact of Antibiotics with Various Target Sites on the Metabolome of Staphylococcus aureus

Dörries

Schlueter

Lalk

2014

Antimicrob Agents Chemother

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“…Although the function of Mur proteins in the antimicrobial stress response of Listeria has not been described in the literature, Mur is the target of antibiotics in Staphylococcus aureus (25).…”

Section: Discussionmentioning

confidence: 99%

Stress Response and Adaptation of Listeria monocytogenes 08-5923 Exposed to a Sublethal Dose of Carnocyclin A

Liu

Basu

Miller

et al. 2014

Appl Environ Microbiol

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Carnocyclin A (CCLA) is an antimicrobial peptide produced by Carnobacterium maltaromaticum ATCC PTA-5313, which can be used to control the growth of Listeria monocytogenes in ready-to-eat meat products. The aim of this research was to elucidate the cellular responses of L. monocytogenes 08-5923 exposed to a sublethal dose of CCLA. Microarray, quantitative reverse transcription-PCR, tandem mass spectrometry, and electron microscopy were used to investigate the alteration in gene expression, protein production, and morphological changes in cells of Listeria following treatment with CCLA. The genes involved in metabolism (baiE, trn, and pykA), cell wall synthesis (murZ and dacB2), and cell division (clpE and divIVA) were upregulated following a 15-min exposure to CCLA as a result of stress responses. Genes involved in cell division, cell wall synthesis, flagellar synthesis, and metabolism were downregulated after 4 h as a result of adaptation. Analysis of total soluble proteins confirmed the downregulation of pykA and gnd after 4 h of exposure to CCLA. The absence of flagella was observed in L. monocytogenes following 30 h of exposure to CCLA. A sublethal dose of CCLA induced adaptation in L. monocytogenes 08-5923 by inhibition of expression of genes and proteins critical for synthesis of cell wall structures and maintaining metabolic functions. Both the mannose-and cellobiose-specific phosphotransferase systems could be targets for CCLA.

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“…aureus Newbond 305, a strain belonging to ST115 and associated to bovine mastitis, by genomic and proteomic comparison with the reference strain RF122. Gene expression analysis by microarray techniques has provided, also, information about global transcript changes [24, 25] or molecular basis of virulence [26] in Staph. aureus .…”

Section: Introductionmentioning

confidence: 99%

Genomic and transcriptomic comparison between Staphylococcus aureus strains associated with high and low within herd prevalence of intra-mammary infection

et al. 2017

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Background Staphylococcus aureus (Staph. aureus) is one of the major pathogens causing mastitis in dairy ruminants worldwide. The chronic nature of Staph. aureus infection enhances the contagiousness risk and diffusion in herds. In order to identify the factors involved in intra-mammary infection (IMI) and diffusion in dairy cows, we investigated the molecular characteristics of two groups of Staph. aureus strains belonging to ST8 and ST398, differing in clinical properties, through comparison of whole genome and whole transcriptome sequencing.ResultsThe two groups of strains, one originated from high IMI prevalence herds and the other from low IMI prevalence herds, present a peculiar set of genes and polymorphisms related to phenotypic features, such as bacterial invasion of mammary epithelial cells and host adaptation. Transcriptomic analysis supports the high propensity of ST8 strain to chronicity of infection and to a higher potential cytotoxicity.ConclusionsOur data are consistent with the invasiveness and host adaptation feature for the strains GTB/ST8 associated to high within-herd prevalence of mastitis. Variation in genes coding for surface exposed proteins and those associated to virulence and defence could constitute good targets for further research.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-017-0931-8) contains supplementary material, which is available to authorized users.

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Transcriptional Signature following Inhibition of Early-Stage Cell Wall Biosynthesis in Staphylococcus aureus

Cited by 12 publications

References 17 publications

Impact of Antibiotics with Various Target Sites on the Metabolome of Staphylococcus aureus

Impact of Antibiotics with Various Target Sites on the Metabolome of Staphylococcus aureus

Stress Response and Adaptation of Listeria monocytogenes 08-5923 Exposed to a Sublethal Dose of Carnocyclin A

Genomic and transcriptomic comparison between Staphylococcus aureus strains associated with high and low within herd prevalence of intra-mammary infection

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