The from the periplasm and extruded out

The
most abundant efflux pumps in bacteria’s are MFS and RND pumps. They are found
in both gram-positive and gram-negative bacteria (Spengler
and Amaral, 2017). Comparatively, gram-negative bacteria
are more prone to resistance because of the presence of large periplasmic space
along with an outer membrane. The drug is sequestered by efflux pump directly
from the periplasm and extruded out even before they reach the cytoplasm (Mahamoud
et al., 2007).

A
nonapeptide derived from Polymyxin B was found to be effective when tested with
erythromycin-resistant Klebsiella
pneumoniae. This peptide conjugate acts by increasing the permeability of
bacterial outer membrane for hydrophobic antibiotics (Tsubery
et al., 2005). Compounds targeting proton motive force
required for the functioning of efflux pumps like verapamil and reserpine can
also be used to increase the efficacy of antibiotics. The major disadvantage of
using these compounds is that the concentration required for their effectiveness
can be neurotoxic. Even the chemically synthesized derivatives of these
compounds were ineffective due to their stability and solubility issues along
with high cost of purification and synthesis (Li et
al., 2004). Many research groups have used peptidomimetics approach
either for altering or inhibiting the function of efflux pumps. Based on this, Microcide
and Daiichi Pharmaceuticals have developed a large family of peptidomimetics
exhibiting properties of efflux pump inhibitors. 

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