Cell Wall Thickening Is a Common Feature of Vancomycin Resistance in
            <i>Staphylococcus aureus</i>

Cui, Longzhu; Ma, Xiaoxue; Sato, Kunitada; Okuma, Keiko; Tenover, Fred C.; Mamizuka, Elsa Masae; Gemmell, C. G.; Kim, Mina; Ploy, Marie-Cécile; Solh, Névine El; Ferraz, Vivian; Hiramatsu, Kazumasa

doi:10.1128/jcm.41.1.5-14.2003

Cited by 424 publications

(386 citation statements)

References 32 publications

Supporting

Mentioning

367

Contrasting

Unclassified

Order By: Relevance

“…A single colony of each strain was grown in broth with increasing levels of vancomycin (0. 5,1,2,4,8,12,16,20,24,28, and 32 g/ml; Sigma Aldrich, St. Louis, MO) until a thick culture (optical density at 600 nm [OD 600 ] Ͼ 1.0) grew (up to 48 h). The strains were then streaked onto BHI agar with the same concentration of vancomycin as that in their most recent growth broth to confirm their stability and resistance level.…”

Section: Methodsmentioning

confidence: 99%

“…Another mechanism of vancomycin resistance involves alterations in the cell wall structure, presumably as a result of mutations. This type of resistance is thought to be mediated by a thickened, poorly cross-linked cell wall that contains sufficient D-Ala-D-Ala targets in the periphery that bind to vancomycin, preventing the drug from accessing more lethal targets at the interior of the cell wall, where cell wall synthesis occurs (15)(16)(17).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Spontaneous Deletion of the Methicillin Resistance Determinant, mecA , Partially Compensates for the Fitness Cost Associated with High-Level Vancomycin Resistance in Staphylococcus aureus

Noto¹,

Fox²,

Archer

2008

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Treatment of infections caused byStaphylococcus aureus is often confounded by the bacterium's ability to develop resistance to chemotherapeutic agents. Methicillin-resistant S. aureus (MRSA) arises through the acquisition of staphylococcal chromosomal cassette mec (SCCmec), a genomic island containing the methicillin resistance determinant, mecA. In contrast, resistance to vancomycin can result from exposure to the drug, a mechanism that is not dependent upon a gene acquisition event. Here we describe three MRSA strains that became resistant to vancomycin during passage in the presence of increasing concentrations of the drug. In each case two derivative strains were isolated, one that had lost mecA and one that retained mecA during passage. Strain 5836VR lost mecA by the site-specific chromosomal excision of SCCmec, while the other two strains (strains 3130VR and VP32) deleted portions of their SCCmec elements in a manner that appeared to involve IS431. Conversion to vancomycin resistance caused a decrease in the growth rate that was partially compensated for by the deletion of mecA. In mixed-culture competition experiments, vancomycin-resistant strains that lacked mecA readily outcompeted their mecA-containing counterparts, suggesting that the loss of mecA during conversion to vancomycin resistance was advantageous to the organism.

show abstract

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Spontaneous Deletion of the Methicillin Resistance Determinant, mecA , Partially Compensates for the Fitness Cost Associated with High-Level Vancomycin Resistance in Staphylococcus aureus

Noto¹,

Fox²,

Archer

2008

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Most studies that have attempted to ascertain the adaptive changes occurring during the transition to growth in the presence of vancomycin have focused on alterations in cell wall synthesis and morphology (8,11,21,27), autolysis (11,28,35), and global transcriptional changes (7,18,19,34). These studies have led to a model of vancomycin resistance in which decreased cell wall turnover and autolysis result in increased cell wall thickness and resistance to vancomycin.…”

mentioning

confidence: 99%

Vancomycin-Intermediate Staphylococcus aureus Strains Have Impaired Acetate Catabolism: Implications for Polysaccharide Intercellular Adhesin Synthesis and Autolysis

Nelson

Rice

Slater

et al. 2007

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The most common mechanism by which Staphylococcus aureus gains resistance to vancomycin is by adapting its physiology and metabolism to permit growth in the presence of vancomycin. Several studies have examined the adaptive changes occurring during the transition to vancomycin-intermediate resistance, leading to a model of vancomycin resistance in which decreased cell wall turnover and autolysis result in increased cell wall thickness and resistance to vancomycin. In the present study, we identified metabolic changes common to vancomycin-intermediate S. aureus (VISA) strains by assessing the metabolic and growth characteristics of two VISA strains (vancomycin MICs of 8 g/ml) and two isogenic derivative strains with vancomycin MICs of 32 g/ml. Interestingly, we observed the parental strains had impaired catabolism of nonpreferred carbon sources (i.e., acetate), and this impairment became more pronounced as vancomycin resistance increased. To determine if acetate catabolism impairment is common to VISA strains, we assessed the ability of VISA and vancomycin-sensitive S. aureus (VSSA) clinical isolates to catabolize acetate. As expected, a significantly greater percentage of VISA strains (71%) had impaired acetate catabolism relative to VSSA (8%). This is an important observation because staphylococcal acetate catabolism is implicated in growth yield and antibiotic tolerance and in regulating cell death and polysaccharide intercellular adhesin synthesis.

show abstract

“…Este hallazgo fundamental no se limita a la cepa Mu50. Cui et al (36) midieron por microscopía electrónica el grosor de la pared celular de 16 cepas VISA recuperadas en siete países diferentes, obteniendo una media de 31,3 nm (desviación estándar 2,62) y las compararon con 7 cepas susceptibles VSSA (vancomycinsusceptible S. aureus) cuyo grosor medio fue de 23,99 nm (desviación estándar 2,04). Además, encontraron una correlación significativa (r = 0,908, p < 0,001) entre la CIM para vancomicina y el grosor de la pared.…”

Section: Resistencia Intermedia a Vancomicina: Cepas Visaunclassified

“…También es destacable la pérdida del gen mutS, que codifica una proteína reparadora del ADN. Estudios anteriores han mostrado que la pérdida de la función de este gen conduce a un fenotipo de hipermutación (100 veces más mutaciones espontáneas comparadas con las cepas mutS+), asociado al desarrollo de resistencia a antibióticos y a una disminución de la adaptabilidad evolutiva (fitness, en la literatura inglesa) (49), lo cual puede explicar los mayores tiempos de generación reportados para la cepa Mu50 en comparación con cepas VSSA (36).…”

Section: Estudios Genómicos En S Aureus Mu50unclassified

Staphylococcus aureus resistente a vancomicina.

Rodríguez¹,

Vesga

2005

biomedica

View full text Add to dashboard Cite

Objetivo. Revisar la evolución y mecanismos moleculares de la resistencia de Staphylococcus aureus a vancomicina. Fuente de los datos. Se consultó la base de datos MEDLINE y se seleccionaron artículos tipo reportes de caso, estudios bioquímicos, de microscopía electrónica y biología molecular pertinentes. Síntesis. Después de casi 40 años de eficacia ininterrumpida de la vancomicina, en 1997 se reportaron los primeros casos de fracaso terapéutico debido a cepas de Staphylococcus aureus con resistencia intermedia, denominadas VISA (concentración inhibitoria mínima, CIM, 8 a 16 µg/ml), así como a cepas con resistencia heterogénea hVISA (CIM global = 4 µg/ml, pero con subpoblaciones VISA), en las cuales la resistencia está mediada por engrosamiento de la pared celular y disminución de su entrecruzamiento, lo que afecta la llegada del antibiótico al blanco principal, los monómeros del peptidoglicano en la membrana plasmática. En 2002 se aisló la primera de las 3 cepas reportadas hasta la fecha con resistencia total al antibiótico, denominadas VRSA (CIM>32 µg/ml), en las que se encontró el transposón Tn1546 proveniente de Enterococcus spp, responsable del reemplazo de la terminación D-Ala-D-Ala por D-Ala-Dlactato en los precursores de la pared celular con pérdida de la afinidad por el glicopéptido. Conclusiones. La resistencia a vancomicina es una realidad en S. aureus, mediada en el caso de VISA por alteraciones en la pared celular que atrapan el antibiótico antes de llegar al sitio de acción, y en el caso de VRSA, por transferencia desde Enterococcus spp. de genes que llevan a la modificación del blanco molecular.Palabras clave: Staphylococcus aureus, peptidoglicano, biosíntesis, antibióticos glicopéptidos, vancomicina, resistencia microbiana a drogas, resistencia a vancomicina. Vancomycin-resistant Staphylococcus aureusThe evolution and molecular mechanisms of vancomycin resistance in Staphylococcus aureus were reviewed. Case reports and research studies on biochemestry, electron microscopy and molecular biology of Staphylococcus aureus were selected from Medline database and summarized in the following review. After almost 40 years of successful treatment of S. aureus with vancomycin, several cases of clinical failures have been reported (since 1997). S. aureus strains have appeared with intermediate susceptibility (MIC 8-16 µg/ml), as well as strains with heterogeneous resistance (global MIC ≤ 4 µg/ml), but with subpopulations of intermediate susceptibility. In these cases, resistance is mediated by cell wall thickening with reduced cross linking. This traps the antibiotic before it reaches its major target, the murein monomers in the cell membrane. In 2002, a total vancomycin resistant strain (MIC ≥ 32 µg/ml) was reported with vanA genes from Enterococcus spp. These genes induce the change of D-Ala-D-Ala terminus for D-Ala-D-lactate in the cell wall precursors, leading to loss of affinity for glycopeptides. Vancomycin resistance in S. aureus has appeared; it is mediated by cell wall modifications that trap the ...

show abstract

Cell Wall Thickening Is a Common Feature of Vancomycin Resistance in Staphylococcus aureus

Cited by 424 publications

References 32 publications

Spontaneous Deletion of the Methicillin Resistance Determinant, mecA , Partially Compensates for the Fitness Cost Associated with High-Level Vancomycin Resistance in Staphylococcus aureus

Spontaneous Deletion of the Methicillin Resistance Determinant, mecA , Partially Compensates for the Fitness Cost Associated with High-Level Vancomycin Resistance in Staphylococcus aureus

Vancomycin-Intermediate Staphylococcus aureus Strains Have Impaired Acetate Catabolism: Implications for Polysaccharide Intercellular Adhesin Synthesis and Autolysis

Staphylococcus aureus resistente a vancomicina.

Contact Info

Product

Resources

About