Introductory Chapter: Pseudomonas aeruginosa - Toward Omnipresence

Antibiotics are extensively used worldwide for treating predominantly gram-negative bacterial infections and also for treating certain gram-positive infections. While the precise mechanism of their bactericidal action is yet to be unraveled, aminoglycosides, for example, act by binding to the RNA component of ribosomes, leading to both mistranslation and ultimate inhibition of protein synthesis. The widespread use of other major classes of antibiotics has resulted in the emergence of resistant bacteria by expediting the course of its evolution [1, 2]. The emergence of resistance to antibiotics is of special concern in the treatment of infections, particularly of systemic nature, by gram-negative organisms narrowing down the options for antibiotic alternatives. The resistance mechanisms displayed by the bacteria can be classified into the following: (a) reduced uptake, (b) increased efflux, (c) enzymatic modification of drug, and (d) drug target modification. Whereas resistance to streptomycin, the first widely used aminoglycoside, is predominantly through mutations in drug targets (mostly in the ribosomal protein rpsL and also in rRNA), resistance to other aminoglycosides appears to utilize a variety of mechanisms. The question arises, whether antibiotic action facilitates the emergence of resistant mutants. For certain other classes of antibiotics that induce the bacterial SOS response either by direct DNA damage (e.g., ciprofloxacin) or through indirect means (e.g., ampicillin), it has been shown that the action of the antibiotic itself plays a significant role in the emergence of mutations that confer resistance. One such mechanism, mistranslation due to defects in the translation apparatus, can promote hypermutagenesis in a phenomenon called translational stressinduced mutagenesis (TSM) raising the possibility that aminoglycoside exposure, by promoting mistranslation, could also elevate mutagenesis. According to the current understanding, TSM is mediated by a low-level mistranslational corruption of the replicative DNA polymerase leading to episodic hypermutagenesis. Exposure of wildtype bacterial cells to sublethal concentrations of an antibiotic increases mutagenic translesion DNA synthesis in vivo, and exposure of certain mutants also increases spontaneous mutagenesis. Exposure of wild-type Pseudomonas aeruginosa PAO1 cells to sublethal concentrations of tobramycin and amikacin, two aminoglycoside antibiotics commonly used to treat P. aeruginosa infections, can elevate spontaneous mutagenesis leading to complications in treating cystic fibrosis patients [3].