PRINCIPAL !NVES7IGaT0R'FRC<jRAM DIRECTOR: Sandra Handwerger , M.D. 
of antibiotic resistance and potential means of cir convent ing 
these . 
In addition, Leuconostoc are of particular interest as a 
reservoir of vancomycin resistant organisms, with the 
possibility for transfer of the genetic determinants of 
resistance to other Gram positive bacteria. Recent evidence 
suggests that mic-roorganisms without significant human 
pathogenicity may act as a source of resistance determinants for 
highly pathogenic -bacteria (47). For example, homology has been 
demonstrated between the chromosome of Streptomvces erythreus 
Jwhich produces erythromycin and is intrinsically resistant to 
erythromycin) and ermD, the MLS resistance element found in 
resistant strains of Bacillus licheniformis , which in turn is. 
related to resistance determinants found in some pathogenic 
streptococci and staphylococci .. These observations have led tc_ 
the suggestion that soil bacteria may exchange genetic material 
with human pathogens, possibly via introduction of insertion 
sequences, and may spread via transpcsons to Gram positive 
pathogens (31) . 
Of greatest concern, however, in the potential role of 
Leuconostoc as "carriers” of genetic determinants encoding 
vancomycin resistance is the recent finding of these organisms 
in -the hospital environment. Leuconostoc species appear to 
reside in the gastrointestinal tract, particularly in patients 
with underlying disease, and recent evidence suggests that 
treatment with vancomycin predisposes to colonization with these 
organisms "(2,37). The gastrointestinal tract is also the site 
from which vancomycin resistant enterococci have been isolated 
(38). In the laboratory, Leuconostoc species have been shewn to 
exchange genetic material residing on plasmids or transpcsons 
with other streptococci, including S. faecalis (29,54,66). The 
possibility that Leuconostoc may exchange genetic determinants 
of antibiotic resistance with other human .gastrointestinal 
pathogens warrants further investigation because of its* 
sicnificant clinical implications .The high prevalence of MLS 
resistance today, three decades after the introduction of these 
antibiotics, demonstrates that once established in Gram positive 
pathogens, resistance determinants may spread widely across 
interspecies and intergeneric barriers. Although vancomycin has 
been used sparingly compared to other antibiotics, factors such 
as increasing methicillin resistance among S. aureus and larger 
numbers of patients at risk for nosocomial infections will 
continue to mandate its more frequent use, increasing selective 
pressure for the spread of resistance. 
C. PRELIMINARY STUDIES: 
I. Mechanism of resistance: 
Previous work by the principal investigator was aimed at 
elucidating the mechanism of resistance to beta-lactam 
antibiotics in Streptococcus pneumoniae . In this case, 
resistance appears to be due to alteration in the antibiotic 
target, i.e. the penicillin binding proteins, membrane bound 
proteins which catalyze the final steps in cell wall assemrly. 
[422] 
Recombinant DNA Research, Volume 13 
