<i>In Vitro</i>
            Studies Indicate a High Resistance Potential for the Lantibiotic Nisin in Staphylococcus aureus and Define a Genetic Basis for Nisin Resistance

Blake, Katy L.; Randall, Chris; O’Neill, Alex J.

doi:10.1128/aac.01077-10

Cited by 70 publications

(89 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We present evidence here that NsaRS fulfils a similar function in S. aureus, responding to cell envelope damage mediated by a variety of antimicrobial agents. A recent study demonstrated that development of spontaneous resistance to nisin in S. aureus is primarily mediated by NsaS (Blake et al, 2011). Nisin is a polycyclic antibacterial peptide produced by Lactococcus lactis and is particularly effective against other Gram-positive bacteria.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, others have shown the importance of NsaS in the development of resistance to nisin (Blake et al, 2011). Finally, a previous study revealed that an nsaS mutant had a fourfold increase in sensitivity to bacitracin (Matsuo et al, 2010).…”

Section: Nsars Regulates Transcription Of the Downstream Transporter mentioning

confidence: 99%

“…GraRS has been described as being important in the resistance of S. aureus to antimicrobial peptides by a variety of mechanisms which remodel the cell wall (Herbert et al, 2007;Li et al, 2007). Reference to NsaRS has only recently appeared in the literature, where it was demonstrated to be important for nisin resistance in S. aureus (Blake et al, 2011). In this study we present a characterization of the NsaRS system and reveal that, as with other IM-HK TCSs, it responds to disruption of the cell envelope and redirects gene expression to mediate resistance.…”

Section: Introductionmentioning

confidence: 99%

“…This is mediated by a variety of processes, including remodelling of cell architecture, and detoxification via transport systems (Mascher, 2006). In S. aureus there are two members of this latter family, the relatively wellstudied GraRS, and the recently named NsaRS (Blake et al, 2011). GraRS has been described as being important in the resistance of S. aureus to antimicrobial peptides by a variety of mechanisms which remodel the cell wall (Herbert et al, 2007;Li et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

NsaRS is a cell-envelope-stress-sensing two-component system of Staphylococcus aureus

et al. 2011

View full text Add to dashboard Cite

Staphylococcus aureus possesses 16 two-component systems (TCSs), two of which (GraRS and NsaRS) belong to the intramembrane-sensing histidine kinase (IM-HK) family, which is conserved within the firmicutes. NsaRS has recently been documented as being important for nisin resistance in S. aureus. In this study, we present a characterization of NsaRS and reveal that, as with other IM-HK TCSs, it responds to disruptions in the cell envelope. Analysis using a lacZ reporter-gene fusion demonstrated that nsaRS expression is upregulated by a variety of cell-envelope-damaging antibiotics, including phosphomycin, ampicillin, nisin, gramicidin, carbonyl cyanide m-chlorophenylhydrazone and penicillin G. Additionally, we reveal that NsaRS regulates a downstream transporter NsaAB during nisin-induced stress. NsaS mutants also display a 200-fold decreased ability to develop resistance to the cell-wall-targeting antibiotic bacitracin. Microarray analysis reveals that the transcription of 245 genes is altered in an nsaS mutant, with the vast majority being downregulated. Included within this list are genes involved in transport, drug resistance, cell envelope synthesis, transcriptional regulation, amino acid metabolism and virulence. Using inductively coupled plasma-MS we observed a decrease in intracellular divalent metal ions in an nsaS mutant when grown under low abundance conditions. Characterization of cells using electron microscopy reveals that nsaS mutants have alterations in cell envelope structure. Finally, a variety of virulence-related phenotypes are impaired in nsaS mutants, including biofilm formation, resistance to killing by human macrophages and survival in whole human blood. Thus, NsaRS is important in sensing cell damage in S. aureus and functions to reprogram gene expression to modify cell envelope architecture, facilitating adaptation and survival.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Nsars Regulates Transcription Of the Downstream Transporter mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

NsaRS is a cell-envelope-stress-sensing two-component system of Staphylococcus aureus

et al. 2011

View full text Add to dashboard Cite

show abstract

“…1). Interestingly, more than one TCS reported that the BceRSAB system was related to susceptibility to nisin, [15][16][17][18] an antimicrobial peptide of the lantibiotic family that is produced by a number of strains of Lactococcus lactis subsp. Lactis.…”

confidence: 99%

Role of two-component systems in the resistance ofStaphylococcus aureusto antibacterial agents

Kawada‐Matsuo

Yoshida²,

Nakamura³

et al. 2011

Virulence

View full text Add to dashboard Cite

Bacterial Stress Responses as Determinants of Antimicrobial Resistance

and

Poole

2016

Stress and Environmental Regulation of Gene Expression and Adaptation in Bacteria

View full text Add to dashboard Cite

In Vitro Studies Indicate a High Resistance Potential for the Lantibiotic Nisin in Staphylococcus aureus and Define a Genetic Basis for Nisin Resistance

Cited by 70 publications

References 50 publications

NsaRS is a cell-envelope-stress-sensing two-component system of Staphylococcus aureus

NsaRS is a cell-envelope-stress-sensing two-component system of Staphylococcus aureus

Role of two-component systems in the resistance ofStaphylococcus aureusto antibacterial agents

Bacterial Stress Responses as Determinants of Antimicrobial Resistance

Contact Info

Product

Resources

About