TABLE 3.

Phenotypic characteristics of clinical and laboratory-induced hVISA and VISA strains compared to related vancomycin-susceptible S. aureus strainsa

Isolate studiedPhenotype (vancomycin MIC [μg/ml])Isolate descriptionPhenotypic feature(s) of hVISA or VISA isolate compared to VSSAReference(s)
MRSA COLVSSAVRSA (VM50) induced from MRSA COL by vancomycin selective pressureGradual alterations in cell wall with increasing resistance; removed vancomycin from broth (vancomycin absorbed into cell wall); reduced growth rate; reduced X linking of cell wall PG; inactivated PBP4; reduced methicillin MIC due to inactivation of mecA; delayed access of vancomycin to active site in division septum245, 315, 317, 319, 320, 322
VM (VM50)VRSA (100)
VM3hVISA/VISA
VM6hVISA/VISA
VM12hVISA/VISA
VM25hVISA/VISA
523VSSALaboratory-induced VISA and VRSA strains; 523teico induced by teicoplanin (teicoplanin MIC of 128 μg per ml)Slower growth, smaller colony size; increased lysostaphin resistance; decreased coagulase activity; increased cell diam; increased cell wall thickness; forms clumps in liquid culture; changes in PG X linking; increased production of PBPs; reduced Triton X-induced autolysis31, 62, 108, 215
523ahVISA/VISA (3)
523cVISA (4)
523kVISA (8)
523teicoVISA (4)
1714VSSA
1714sVRSA (32)
1725VSSA
1725wVISA (16)
Mu3hVISA (2-4)First reported hVISA and VISA strainsvanA, vanB, and vanC1 to vanC3 negative; increased production of PBP2 and PBP2′; activated cell wall synthesis; increased glutamate-containing muropeptides; correlation between cell wall thickness and vancomycin resistance; Mu50 reduced resistance after 15 days of serial passage; reduced whole-cell autolytic activity; vancomycin clogging of cell wall with anomalous diffusion29, 56, 58, 59, 108, 109, 362
Mu50VISA (8)
Mu50ωVSSA/hVISAMu50ω isolated 1 year later from same patient as Mu50
SA137/93AVISA (8)Germany; SA137/93A clinical isolate; other spontaneous mutants with increased and decreased resistancesIncreased cell wall thickness; reduced beta-lactam resistance; increased cell wall X linking in SA137/93G267
SA137/93GVISA (12)
SA137/93G1VSSA
JKD6000VSSA (2)Paired isolates from 5 patients with persistent MRSA infections and vancomycin treatment failurevanA, vanB, and vanC1 to vanC3 negative; thickened cell wall; reduced agr activity; reduced autolytic activity (4/5); reduced in vitro biofilm formation121
JKD6001VISA (4)
JKD6004VSSA (1)
JKD6005hVISA (2)
JKD6009VSSA (1)
JKD6008VISA (4)
JKD6021VSSA (1)
JKD6023VISA (4)
JKD6052VSSA (1)
JKD6051hVISA (2)
PC-1hVISA (2)Paired isolates from patient with vancomycin treatment failureReduced vancomycin concn in broth culture of PC-3, recovered from staphylococcal cell wall; cell wall thickening; reduced resistance after 15 days of serial passage; no increase in glutamate-containing muropeptides; reduced Triton X-induced autolysis29, 31, 32, 58, 284, 316
PC-3VISA (8)
BB225VSSA (1)Series of laboratory-induced VISA strainsNo change in oxacillin MIC; increased cell wall thickness (with vancomycin); increased doubling time; reduced lysostaphin susceptibility of whole cells but increased susceptibility of purified cell walls; reduced autolytic activity in part due to lower activity of VISA autolysin extracts; reduced alt expression; removed vancomycin from broth culture; no mutS mutations58, 160, 221, 250
BB225V3VISA (4)
BB270VSSA (1)
BB270V15VISA (12)
13136pmVSSA (1)
13136pmV5VISA (4)
13136pm+VSSA (1.5)
13136pm+V20VISA (16)
SH108VSSA (2)
SH108V5VISA (6)
BB399VSSA (2)
BB399V12VISA (12)
BB568VSSA (1)
BB568V15VISA (12)
COLVSSA (2)
COLV10VISA (8)
Others
MIVISA (6)Michigan VISA isolate, July 1997, CAPD-associated peritonitisReduced resistance after 15 days of serial passage; cell wall thickening; increased extracellular matrix; increased glutamate-containing muropeptides; reduced Triton X-induced autolysis29, 31, 32, 58, 326
NJVISA (5)New Jersey VISA isolate, August 1997, bacteremiaReduced resistance after 15 days of serial passage; cell wall thickening; increased extracellular matrix; increased glutamate-containing muropeptides; reduced Triton X-induced autolysis29, 31, 32, 58, 326
IL-AhVISAVISA emerged from hVISA during 13 days of persistent bacteremiaCell wall thickening; no increase in glutamate-containing muropeptides; increased cell wall thickness; reduced lysostaphin susceptibility; reduced Triton X-induced autolysis; increased cell wall X linking; reduced Triton X-induced autolysis30-32, 58
IL-FVISA (8)
AMC11094VISA (8)South Korea, clinical isolateCell wall thickening58, 158
99/3759-VVISA (8)Scotland, UKCell wall thickening58
99/3700-WVISA (8)
LIM-1VSSA (2)France; isolated from patient with persistent infection and failed teicoplanin therapy; all blood culture isolates except LIM-3 (purulent discharge)Cell wall thickening; vanA, vanB, and vanC1 to vanC3 negative58, 258
LIM-2VISA (8)
LIM-3VISA
LIM-4VISA
28160VISA (8)South AfricaCell wall thickening58, 79
JH1VSSA (1)Baltimore, MD; series of blood culture isolates from patient with endocarditis who failed vancomycin therapy; JH14, valve isolateCell wall thickening; decreased wall X linking; reduced PBP4; decreased cell wall turnover and autolysis; changes in wall teichoic acids; delayed access of vancomycin to active site in division septum245, 314, 318
JH2VISA (4)
JH3VISA (4)
JH5VISA (6)
JH6VISA (8)
JH9VISA (8)
JH14VISA (8)
BR1VISA (8)Clinical isolates from BrazilCell wall thickening; vanA, vanB, and vanC1 to vanC3 negative58, 235
BR2VISA (8)
BR3VISA (8)
BR4VISA (8)
BR5VISA (8)
98141VISA (8)France, clinical isolateCell wall thickening49, 58
SF1VSSA (1)San Francisco, CA, paired clinical isolates; endocarditis, failed vancomycin therapySignificant reduction in efficacy of vancomycin against SF2 in rabbit endocarditis model213
SF2hVISA (2)
MRGR3VSSA (1), TSSA (0.5)Teicoplanin-resistant subclones emerged in rat model of foreign-body infection without antibiotic exposure; stable clones selected on teicoplanin-containing medium (14-4 and 17-2); 14-4rev, spontaneous revertantUnstable resistance in rat model without antibiotic exposure; increased fibronectin-mediated adherence; reduced autolytic activity; reduced extracellular hydrolase activity; reduced agr268, 269, 367
14-4VISA (4; teicoplanin, 16)
14-4revVSSA (1)
17-2VISA (4; teicoplanin, 16)
RN6607VSSA (1)RN strains laboratory inducedReduced agr activity in VISA and hVISA; reduced in vitro bactericidal activity of vancomycin in agr-null vs parent strains; agr-null increased propensity for hVISA; reduced agr activity associated with reduced autolysis and resistance to tPMP294, 295
RN6607VhVISA (2)A5937 and A5940 clinical isolate pair
RN9120VSSA (1)
RN9120VhVISA (2)
RN9120V-GISAVISA (8)
A5937VSSA (2)
A5940VISA (4)
SA113TSSA (teicoplanin, 3)In vitro-derived strains, teicoplanin selectedSlower growth; thickened cell wall; increased N-acetylglucosamine incorporation; reduced fitness in resistant strain201
NM18Teicoplanin MIC, 16
NM30Teicoplanin MIC, 48
NM67Teicoplanin MIC, 64 (vancomycin, 24)
Hershey MCSeries of isolates from one patientReduced muropeptide cross-linking; reduced O-acetylation of muramic acid151
1VSSA
3VSSA
10VISA (daptomycin resistant)
25VISA
  • a Note that some laboratory-induced isolates had MICs of vancomycin in the resistant range despite the absence of the vanA operon. CAPD, continuous ambulatory peritoneal dialysis; tPMP, thrombin-induced platelet microbicidal protein; TSSA, teicoplanin-sensitive S. aureus.