Effect of Promoter Region Mutations and
 mgrA
 Overexpression on Transcription of
 norA
 , Which Encodes a
 Staphylococcus aureus
 Multidrug Efflux Transporter

Kaatz, Glenn W.; Thyagarajan, Rama; Seo, Susan M.

doi:10.1128/aac.49.1.161-169.2005

Cited by 79 publications

(73 citation statements)

References 43 publications

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“…MgrA contains a typical HTH DNA-binding motif and is a member of the MarR family of transcriptional regulators. Similar to CmeR, MgrA also functions as both a repressor and an activator for various genes in Staphylococcus (16,27,43). A recent DNA microarray study indicated that MgrA affects the expression of 355 genes in multiple functional categories in S. aureus (26).…”

Section: Discussionmentioning

confidence: 99%

CmeR Functions as a Pleiotropic Regulator and Is Required for Optimal Colonization of Campylobacter jejuni In Vivo

Guo¹,

Wang²,

Shi³

et al. 2008

J Bacteriol

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Section: Discussionmentioning

confidence: 99%

CmeR Functions as a Pleiotropic Regulator and Is Required for Optimal Colonization of Campylobacter jejuni In Vivo

Guo¹,

Wang²,

Shi³

et al. 2008

J Bacteriol

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“…MgrA regulates expression of genes encoding other Nor efflux pumps and virulence factors (8,20,(22)(23)(24)(32)(33)(34), but it does not affect regulation of the opp1-norD operon. Our data show that opp1-norD expression was comparable in S. aureus MW2 and MW2 mgrA mutant in both rich medium and under low free iron conditions (data not shown), suggesting that regulation of opp1-norD is independent of MgrA.…”

Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus NorD, a Putative Efflux Pump Coregulated with the Opp1 Oligopeptide Permease, Contributes Selectively to Fitness In Vivo

Ding

Lee

et al. 2012

J Bacteriol

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c Staphylococcus aureus readily infects humans, causing infections from mild superficial skin infections to lethal bacteremia and endocarditis. Transporters produced by S. aureus allow the pathogen to adapt to a variety of settings, including survival at sites of infection and in the presence of antibiotics. The native functions of many transporters are unknown, but their potential dual contribution to fitness and antimicrobial resistance highlights their importance in staphylococcal infections. Here, we show that S. aureus NorD, a newly recognized efflux pump of the major facilitator superfamily, contributes to fitness in a murine subcutaneous abscess model. In community-associated methicillin-resistant S. aureus (CA-MRSA) strain MW2, norD was selectively upregulated 36-fold at the infection site relative to growth in vitro, and the norD mutant demonstrated significant fitness impairment in abscesses, with fitness 20-to 40-fold lower than that of the parent MW2 strain. Plasmid-encoded NorD could complement the fitness defect of the MW2 norD mutant. Chromosomal norD expression is polycistronic with the upstream oligopeptide permease genes (opp1ABCDF), which encode an ABC oligopeptide transporter. Both norD and opp1 were upregulated in abscesses and iron-restricted culture medium and negatively regulated by Fur, but only NorD contributed to fitness in the murine abscess model. Staphylococcus aureus is a versatile pathogen that causes a variety of diseases from food poisoning, skin infections, and abscesses to lethal bacteremia and endocarditis (21). Its adaptability is facilitated by a range of virulence factors and by factors that contribute to its survival and fitness in multiple environments within the host (2). Among the contributors to S. aureus fitness are a range of transmembrane transporters that can mediate uptake of nutrients or export of metabolites and toxic substances, including in some cases export of antimicrobial agents causing antimicrobial resistance (5,9,15,16,26,28).We found previously that several staphylococcal efflux pumps were selectively overexpressed within the milieu of experimental subcutaneous abscesses and that these pumps not only contributed to antimicrobial resistance when overexpressed in vitro but also contributed to bacterial survival within the abscess in the absence of antimicrobial agents (12). Both NorB and Tet38, members of the major facilitator superfamily (MFS) of secondary transporters encoded on the S. aureus chromosome, contributed selectively to fitness in the abscess environment and conferred low-level resistance to fluoroquinolones and tetracycline, respectively.In order to identify other transporters that might also be important for bacterial survival in this environment, we evaluated the MFS transporter NorD. Like norB and tet38, norD expression was selectively upregulated in abscesses. Herein, we present data indicating that NorD contributes substantially to S. aureus fitness in an abscess infection model, and we identified a low-iron environment as a potential ...

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“…In addition to regulating virulence determinants, MgrA represses the expression of several efflux systems (i.e., NorA, NorB, NorC, and Tet38) that confer resistance to multiple antibiotics (111,224,225). MgrA is a member of the MarR family of regulatory proteins and, as such, has a dimerization domain and a conserved helix-turnhelix domain (28).…”

Section: Mgramentioning

confidence: 99%

At the Crossroads of Bacterial Metabolism and Virulence Factor Synthesis in Staphylococci

Somerville

Proctor

2009

Microbiol Mol Biol Rev

329

348

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SUMMARY Bacteria live in environments that are subject to rapid changes in the availability of the nutrients that are necessary to provide energy and biosynthetic intermediates for the synthesis of macromolecules. Consequently, bacterial survival depends on the ability of bacteria to regulate the expression of genes coding for enzymes required for growth in the altered environment. In pathogenic bacteria, adaptation to an altered environment often includes activating the transcription of virulence genes; hence, many virulence genes are regulated by environmental and nutritional signals. Consistent with this observation, the regulation of most, if not all, virulence determinants in staphylococci is mediated by environmental and nutritional signals. Some of these external signals can be directly transduced into a regulatory response by two-component regulators such as SrrAB; however, other external signals require transduction into intracellular signals. Many of the external environmental and nutritional signals that regulate virulence determinant expression can also alter bacterial metabolic status (e.g., iron limitation). Altering the metabolic status results in the transduction of external signals into intracellular metabolic signals that can be “sensed” by regulatory proteins (e.g., CodY, Rex, and GlnR). This review uses information derived primarily using Bacillus subtilis and Escherichia coli to articulate how gram-positive pathogens, with emphasis on Staphylococcus aureus and Staphylococcus epidermidis, regulate virulence determinant expression in response to a changing environment.

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Effect of Promoter Region Mutations and mgrA Overexpression on Transcription of norA , Which Encodes a Staphylococcus aureus Multidrug Efflux Transporter

Cited by 79 publications

References 43 publications

CmeR Functions as a Pleiotropic Regulator and Is Required for Optimal Colonization of Campylobacter jejuni In Vivo

CmeR Functions as a Pleiotropic Regulator and Is Required for Optimal Colonization of Campylobacter jejuni In Vivo

Staphylococcus aureus NorD, a Putative Efflux Pump Coregulated with the Opp1 Oligopeptide Permease, Contributes Selectively to Fitness In Vivo

At the Crossroads of Bacterial Metabolism and Virulence Factor Synthesis in Staphylococci

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