Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Oct 13:7:1601.
doi: 10.3389/fmicb.2016.01601. eCollection 2016.

Molecular Events for Promotion of Vancomycin Resistance in Vancomycin Intermediate Staphylococcus aureus

Qiwen Hu  1 , Huagang Peng  1 , Xiancai Rao  1
Affiliations
Review

Molecular Events for Promotion of Vancomycin Resistance in Vancomycin Intermediate Staphylococcus aureus

Qiwen Hu et al. Front Microbiol. .

Abstract

Vancomycin has been used as the last resort in the clinical treatment of serious Staphylococcus aureus infections. Vancomycin-intermediate S. aureus (VISA) was discovered almost two decades ago. Aside from the vancomycin-intermediate phenotype, VISA strains from the clinic or laboratory exhibited common characteristics, such as thickened cell walls, reduced autolysis, and attenuated virulence. However, the genetic mechanisms responsible for the reduced vancomycin susceptibility in VISA are varied. The comparative genomics of vancomycin-susceptible S. aureus (VSSA)/VISA pairs showed diverse genetic mutations in VISA; only a small number of these mutations have been experimentally verified. To connect the diversified genotypes and common phenotypes in VISA, we reviewed the genetic alterations in the relative determinants, including mutations in the vraTSR, graSR, walKR, stk1/stp1, rpoB, clpP, and cmk genes. Especially, we analyzed the mechanism through which diverse mutations mediate vancomycin resistance. We propose a unified model that integrates diverse gene functions and complex biochemical processes in VISA upon the action of vancomycin.

Keywords: genetic mechanisms; genotypes; molecular events; vancomycin; vancomycin intermediate Staphylococcus aureus.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The mode of action of vancomycin in S. aureus. By binding to the C-teminal D-Ala-D-Ala residues of the pentapeptide, vancomycin inhibits the cross bridge formation between pentapeptide and pentaglycine. GlcNAc, N-acetylglucosamine; MurNAc, N-Acetylmuramic acid.
Figure 2
Figure 2
Timeline indicates the year in which an event occurred or was reported. The increased use of vancomycin in the USA, France, Italy, Germany, the United Kingdom, and the Netherlands was shown as tons of vancomycin in the y-axis, which was modified from reference Levine (2006).
Figure 3
Figure 3
Molecular events in VISA. Key regulatory proteins and cell wall synthesis processes and their enzymes related to vancomycin resistance in VISA. WTA, wall teichoic acid; LTA, lipoteichoic acid; Glc, glucose; GlcN-6-P, glucosamine-6-phosphate; GlcNAc, N-acetylglucosamine; MurNAc, N-Acetylmuramic acid; DAG, diacylglycerol.
See this image and copyright information in PMC

References

    1. Alexander E. L., Gardete S., Bar H. Y., Wells M. T., Tomasz A., Rhee K. Y. (2014). Intermediate-type vancomycin resistance (VISA) in genetically-distinct Staphylococcus aureus isolates is linked to specific, reversible metabolic alterations. PLoS ONE 9:e97137. 10.1371/journal.pone.0097137 - DOI - PMC - PubMed
    1. Antony S. J. (2014). Case series describing an outbreak of highly resistant vancomycin Staphylococcus aureus (possible VISA/VRSA) infections in orthopedic related procedures in Guatemala. Infect. Disord. Drug Targets 14, 44–48. 10.2174/1871526514666140522115220 - DOI - PubMed
    1. Atilano M. L., Pereira P. M., Yates J., Reed P., Veiga H., Pinho M. G., et al. (2010). Teichoic acids are temporal and spatial regulators of peptidoglycan cross-linking in Staphylococcus aureus. Proc. Natl. Acad. Sci. U.S.A. 107, 18991–18996. 10.1073/pnas.1004304107 - DOI - PMC - PubMed
    1. Bae T., Schneewind O. (2006). Allelic replacement in Staphylococcus aureus with inducible counter-selection. Plasmid 55, 58–63. 10.1016/j.plasmid.2005.05.005 - DOI - PubMed
    1. Belcheva A., Verma V., Golemi-Kotra D. (2009). DNA-binding activity of the vancomycin resistance associated regulator protein VraR and the role of phosphorylation in transcriptional regulation of the vraSR operon. Biochemistry 48, 5592–5601. 10.1021/bi900478b - DOI - PubMed