Disease relevance of Vancomycin Resistance

• The development of vancomycin resistance in a patient with methicillin-resistant Staphylococcus aureus infection [1].
• Phosphinate analogs of D-, D-dipeptides: slow-binding inhibition and proteolysis protection of VanX, a D-, D-dipeptidase required for vancomycin resistance in Enterococcus faecium [2].
• Emergence of vancomycin resistance in the genus Streptococcus: characterization of a vanB transferable determinant in Streptococcus bovis [3].
• We also show that the growth defect can be partially restored by expression of the d-alanyl-d-alanine-forming Ddl ligase from Lactococcus lactis, or by supplementation with various d-2-hydroxy acids but not d-2-amino acids, leading to variable vancomycin resistance levels [4].
• Exemplifying these trends are methicillin-resistance in Staphylococcus aureus, vancomycin-resistance in coagulase-negative staphylococci, relative resistance to penicillin among pneumococci, aminoglycoside-resistance in viridans streptococci, and resistance to both beta-lactams and aminoglycosides in enterococci [5].

High impact information on Vancomycin Resistance

• VanX is a zinc-dependent D-alanyl-D-alanine dipeptidase that is a critical component in a system that mediates transposon-based vancomycin resistance in enterococci [6].
• These enzymes are the target of the pentasaccharide antibiotic moenomycin as well as the proposed target of certain glycopeptides that overcome vancomycin resistance [7].
• The molecular basis of vancomycin resistance in clinically relevant Enterococci: crystal structure of D-alanyl-D-lactate ligase (VanA) [8].
• D-Ala-D-Ala ligases from glycopeptide antibiotic-producing organisms are highly homologous to the enterococcal vancomycin-resistance ligases VanA and VanB [9].
• The overall genetic strategy described here may also be useful for studying interactions of other components of the vancomycin resistance and P1 signal transduction pathways, other two-component regulatory systems, and other interacting proteins [10].

Chemical compound and disease context of Vancomycin Resistance

• BACKGROUND: The restriction of vancomycin hydrochloride use is recommended as a measure to decrease the emergence of vancomycin resistance in gram-positive organisms; however, vancomycin also is the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) infections [11].
• We assessed the ability of gene transfer to reverse vancomycin resistance in class A (VanA) glycopeptide-resistant Enterococcus faecalis [12].
• Geographic distribution of a large mobile element that transfers ampicillin and vancomycin resistance between Enterococcus faecium strains [13].
• Campylobacter blood agar with clindamycin incubated in 6% CO2 served as a medium to both screen for vancomycin resistance and select for presumptive enterococci [14].
• Impact of sigB mutation on Staphylococcus aureus oxacillin and vancomycin resistance varies with parental background and method of assessment [15].

Biological context of Vancomycin Resistance

• Multicopy plasmids pAT80 (vanR vanS vanH vanA vanX) and pAT382 (vanR vanS vanH vanA vanX vanY) conferred similar levels of vancomycin resistance to JH2-2 [16].
• Enterococcus faecalis strain WCH9 displays a moderate level of resistance to vancomycin (MIC = 16 microgram/ml) and full susceptibility to teicoplanin but is negative by PCR analysis using primers specific for all known enterococcal vancomycin resistance genotypes (vanA, vanB, vanC, vanD, and vanE) [17].
• In 2002, the first two clinical isolates of vancomycin-resistant Staphylococcus aureus (VRSA) containing vanA were recovered in Michigan and Pennsylvania. Tn1546, a mobile genetic element that encodes high-level vancomycin resistance in enterococci, was present in both isolates [18].
• In vivo emergence of subpopulations expressing teicoplanin or vancomycin resistance phenotypes in a glycopeptide-susceptible, methicillin-resistant strain of Staphylococcus aureus [19].
• Thirty-six VanB glycopeptide-resistant Enterococcus faecium isolates were collected from patients in five different hospitals in Taiwan. The vancomycin resistance genes were amplified by the long vanB PCR, which amplifies the 6,373-bp vanB gene cluster including the vanR(B2), vanS(B2), vanY(B2), vanW(B2), vanH(B2), vanB2, and vanX(B2) genes [20].

Anatomical context of Vancomycin Resistance

• Of 115 methicillin-resistant Staphylococcus strains collected from sputum specimens, 34 strains reduced susceptibility to vancomycin, 9 of which emerged as heterogeneous vancomycin-resistant strains (hetero-VRS), with various degrees of vancomycin resistance at a frequency of 10(-6) or higher [21].
• Membranes isolated from vancomycin-resistant ciprofloxacin-resistant cultures grown with vancomycin and ciprofloxacin at < or = 8 mg/L (0.125 x MIC) expressed a 39.5-kDa membrane protein involved in the expression of vancomycin resistance, but the protein was not detected in membranes from cultures grown in ciprofloxacin 16 mg/L [22].
• CONCLUSIONS: Structural differences at subsite 2 of the D-alanine-D-lactate ligase help explain a substrate specificity shift (D-alanine to D-lactate) leading to remodeled cell wall peptidoglycan and vancomycin resistance in Gram-positive pathogens [23].

Associations of Vancomycin Resistance with chemical compounds

• Whereas major advances have been made in our understanding of methicillin and vancomycin resistance mechanisms, we still need to identify the sources and reservoirs of the genetic determinants of resistance and to discover how they disseminate in the environment [24].
• Antibiotic resistances among the infections included high-level gentamicin resistance (26%), ampicillin resistance (10%), and vancomycin resistance (8%) [25].
• These combined observations reflect the relationship which seems to exist between the new D-lactate peptidoglycan precursor, synthesized when the vancomycin resistance is expressed, and the affinity of the different PBPs for this precursor [26].
• In terms of resistance (highest concentration of antibiotic permitting growth), the levels of vancomycin resistance of six strains ranged from 0.2 to 1.0 microgram/ml, and the level of erythromycin resistance of these strains was 0.02 or 0.05 micrograms/ml [27].
• The results indicate that mecA--the genetic determinant of oxacillin resistance--while essential for oxacillin resistance, is not involved with the expression of vancomycin resistance [28].

Gene context of Vancomycin Resistance

• One of the predicted mobile elements is a previously unknown vanB vancomycin-resistance conjugative transposon [29].
• Although resistance in these strains is not the result of the transfer of enterococcal vancomycin resistance genes (vanA or vanB), the clonal dissemination of MRSA strains with vancomycin-resistant subpopulations is obviously undesirable [30].
• Cloning of the gyrB gene of BM4405 restored vancomycin resistance to BM4405-1 [31].
• Complementation of these two GISA strains with a functional tcaA allele reduced their levels of teicoplanin and vancomycin resistance five- to eightfold and twofold, respectively [32].
• Mutation of sigB caused a decrease in vancomycin resistance in two laboratory derived glycopeptide-intermediate S. aureus strains [15].

Analytical, diagnostic and therapeutic context of Vancomycin Resistance

• It has been concluded that bacteriocin-producing E. faecium strains lacking hemolytic activity and not carrying cytolysin nor vancomycin resistance genes may be useful as starter cultures, cocultures, or probiotics [33].
• To locate the determinant for high vancomycin resistance, the electrophoresis profile was further analyzed by Southern blot using the digoxigenin (DIG)-labeled vanA gene probe [34].

References