Molecular Strategies of Staphylococcus aureus for Resisting Antibiotics
Susan Boyle-Vavra and Robert S Daum
from: Staphylococcus: Genetics and Physiology (Edited by: Greg A. Somerville). Caister Academic Press, U.K. (2016) Pages: 249-300.
Since there is no vaccine to prevent Staphylococcus aureus infection, clinicians must heavily rely on antibiotics to treat S. aureus infections. However, S. aureus has been able to elude every antibiotic that has been widely introduced into clinical practice. This Chapter summarizes some of the most important antibiotics that have been used in the therapy of S. aureus infection since the golden age of antibiotic discovery, starting with the introduction of penicillin in 1940s and methicillin in the 1960s. The emphasis of the chapter is placed on the variety of resistance mechanisms that S. aureus has evolved to elude antibiotics and the mobile genetic elements that allow horizontal transfer of resistance genes between strains and between species. S. aureus strains have become resistant to antibiotics by a wide variety of mechanisms. At the genetic level, resistance has occurred through acquiring point mutations in the chromosomal gene or genes encoding the antibiotic target or by horizontal gene exchange resulting in the acquisition of new genes that confer resistance. Examples of antibiotic resistance strategies that have evolved in S. aureus include: a) acquisition of spontaneous point mutations in the native target that decreases the binding of the antibiotic, b) acquisition of a gene encoding an enzyme that inactivates the antibiotic, c) acquisition of an antibiotic-insensitive target that can bypass the antibiotic's effect by replacing the function of the native target, d) acquisition of an enzyme that modifies the target thereby blocking access of the antibiotic to the target, e) expressing a protein or proteins that transport(s) a drug out of the cytoplasm (for instance via an efflux pump), thereby reducing its cytoplasmic concentration, f) acquiring mutations that alter the bacterial surface properties that, for instance, decrease the interaction of the antibiotic with the bacteria, g) ribosomal protection without target modification. Antibiotic strategies that target an essential process in bacteria place strong selective pressure that ultimately results in resistance. Strategies that potentiate reliable antibiotics or that delay resistance development could increase the lifespan and usefulness of old and new antimicrobial agents. Also, by better understanding how bacteria cause disease and death, it will be possible to design treatment strategies that ameliorate the toxic effects of the bacteria on the host rather than by directly killing the bacteria read more ...