V..I 3 1 ;i No. 3 
mi:dii:ai. in rr.i.i.u ; kn<;e — i.i.cu.kf y kt al. 
lli.il this sli.iinl extrusive homology (Lis'. 2). The two 
plasmids were apparently not self-transfer 'aide to oth- 
er enterococci but could be introduced by transforma- 
tion into S. sunlit is. Resistance to glycoprptidcs was 
inducible in the original strains and in the transfor- 
mants by subinhibitory concentrations of vancomycin 
and tcicoplauin (Table 2). 
The bioihemieal mechanism of resistance to vanco- 
mycin and tcicoplanin in E. Jatcium B.M H47 and 
HMH52 is unknown. Enzymic modification of the 
drugs may occur; however, inactivation of the anti- 
biotics was not detected by microbiologic techniques. 
Alteration of the target site — i.c. , the D-alunyl-D- 
alanine terminus ol A’-aeetylinuramyl-penlapeptide 35 
— impel meability to the drugs, and a bypass mecha- 
nism are under investigation. 
There was no cross resistance between the glyco- 
peptide and lipopeptidc antibiotics in the strains we 
studied. The activity of LY 146032 was not affected by 
plasmid-mediated resistance to high levels of vanco- 
mycin and tcicoplanin, and a plasmid-cured deriva- 
tive of an LY 146032 -resistant mutant was susceptible 
to both antibiotics (Table 2). This dissociated resist- 
ance may be the result of a difference in the mecha- 
nism of action of the two groups of antibiotics. 30 The 
lack of cross resistance between glycopeptidcs and 
lipopcplidcs is clinically important because of the 
limited alternative therapeutic options against such 
strains as BM4147 and B.M4I52, which arc resistant 
to many antibiotics (Table 3). The fact that we were 
able to obtain one-step mutants resistant to LY 146032 
from strains resistant to glycopeptide but not from 
susceptible cells is cause for concern. The reason for 
this apparent facilitation of the emergence of resistant 
mutants remains obscure. 
Resistance to gly copcptides is rare in gram-positive 
cocci. The stepwise changes in the susceptibility to 
vancomycin of S. haemofjlicus 7 do not favor a plasmid- 
mediated process. This contrasts with the characteris- 
tics of the clinical isolates described here, and it would 
be interesting to determine the genetic basis of the 
resistance to vancomycin in the strains of E. farcium 
and E.faecr.'.is recently responsible for an outbreak of 
infections." In any case, enterococci can no longer be 
considered to be uniformly susceptible to glycopeptide 
antibiotics. 
W’c arc indebted to L. Dcvriesc for help in identification of bacte- 
ria and to R Williamson for determination of penicillin-binding 
protein patterns. 
AW aJd.J in proof: Since submission of this paper, we have ob- 
tained conjugal transfer of plasmid p I P8 1 7 to another E. /atrium 
strain. 
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Recombinant DNA Research, Volume 13 
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