Synopses

Multiple-Drug Resistant Enterococci:  The Nature of the Problem and an Agenda for the Future

Mark M. Huycke,*† Daniel F. Sahm,‡ and Michael S. Gilmore†
*University of Oklahoma Health Sciences Center, Oklahoma, USA; †Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA; and ‡MLR Pharmaceutical Services, Inc., Reston, Virginia, USA

Back to article Figure 1. Epidemiology of enterococcal infection based on 15,203 susceptibility results obtained by The Surveillance Network (TSN) Database-USA, 1995 to Sep 1, 1997. The increase in total numbers between 1995 and 1996 represents additional reporting centers coming on line. Numbers for 1997 represent total collected for the partial year to Sep 1, 1997.

Back to article Figure 2. Virulence traits and their association with enterococcal species.

Back to article Figure 3. Cytolysin favors the appearance of circulating enterococci. In this experiment, 107 CFU of E. faecalis, either cytolytic FA2-2(pAM714) (60) or noncytolytic FA2-2(pAM771) (64), were intraperitoneally injected (45) into groups of five BalbC mice. Viable bacteria in liver, spleen, and the bloodstream were enumerated 48 hrs following injection, and significance assessed by Student's t-test. (P. Coburn, L.E. Hancock, and M.S. Gilmore, in preparation).

Back to article Figure 4. Cytolysin is expressed and processed through a complex maturation pathway (64). The cytolysin precursors, CylLL and CylLS, are ribosomally synthesized. The putative modification protein, CylM, is required for the expression of CylLL and CylLS in an activatable form, and the secreted forms, CylLL and CylLS were recently shown to possess the amino acid lanthionine as the result of posttranslational modification (64). CylLL and CylLS both are secreted by CylB (65), which is accompanied by an initial proteolytic trimming event (64) converting each to CylLL' and CylLS', respectively. Once secreted, CylLL' and CylLS' are both functionally inactive until six amino acids are removed from each amino terminus. This final step in maturation is catalyzed by CylA (64), a subtilisin-type serine protease. Since this final catalytic event is essential, occurs extracellularly, and is catalyzed by a class of enzyme for which a substantial body of structural information exists, it represents an ideal therapeutic target. As shown in Figure 3, inhibition of cytolysin by mutation (or potentially by therapeutic intervention) results in a reduction by several orders of magnitude in the number of circulating organisms.

Top of Page  | Current Issue  |  Upcoming Issue  |  Past Issue  |  Search   |  Home

NCID Home
CDC Home

Emerging Infectious Diseases
National Center for Infectious Diseases
Centers for Disease Control and Prevention
Atlanta, GA

URL: http://www.cdc.gov/ncidod/EID/vol4no2/huyckeg.htm