Antibiotic Resistance due to Reduced Uptake

The introduction of antibiotic therapy for the treatment of bacterial infections has led to a greatly increased human life span compared to that in the pre-antibiotic era. However, a disturbing trend has also been noted in that, within a very short period of time following the introduction of a new antibiotic, resistance to that antibiotic begins to emerge, a factor that is becoming increasingly meaningful as the discovery of new antibiotics wanes [1–3]. There are a number of mechanisms by which a bacterium may become resistant to a particular antibiotic. Generally these include, but are not limited to, modification of the drug to render it inactive, modification of the drug target, such that it is incapable of interacting with the drug and decreased uptake of the antibiotic into the cell, due to reduced transport and/or increased efflux. Recent functional genomic studies have also implied that antibiotics may have more complex mechanisms of action than first thought and we are beginning to appreciate that in addition to the mutation of primary targets, subtle mutations in secondary targets are likely to be influential [4, 5]. Moreover, a growing body of evidence suggests that the temporary changes in susceptibility associated with the phenomenon of adaptive resistance may also be important for the global rise in bacterial resistance to antimicrobial compounds [6]. This chapter will focus on the contribution of a decreased antibiotic uptake to an increase in antibacterial resistance.