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The protein synthesis inhibition of aminoglycosides does not usually produce a bactericidal

effect, let alone a rapid one as is frequently observed on susceptible Gram-negative bacilli.

Aminoglycosides competitively displace cell biofilm-associated Mg2+

and Ca2+

that link thepolysaccharides of adjacent lipopolysaccharide molecules. "The result is shedding of cell

membrane blebs, with formation of transient holes in the cell wall and disruption of the normal

permeability of the cell wall. This action alone may be sufficient to kill most susceptible Gram-negative bacteria before the aminoglycoside has a chance to reach the 30S ribosome."

The antibacterial properties of aminoglycosides were believed to result from inhibition ofbacterial protein synthesis through irreversible binding to the 30S bacterial ribosome. This

explanation, however, does not account for the potent bactericidal properties of these agents,

since other antibiotics that inhibit the synthesis of proteins (such as tetracycline) are not

bactericidal. Recent experimental studies show that the initial site of action is the outer bacterialmembrane. The cationic antibiotic molecules create fissures in the outer cell membrane, resulting

in leakage of intracellular contents and enhanced antibiotic uptake. This rapid action at the outer

membrane, it is presumed, accounts for most of the bactericidal activity. Energy is needed for

aminoglycoside uptake into the bacterial cell. Anaerobes have less energy available for thisuptake, so aminoglycosides are less active against anaerobes

Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria,

such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some Mycobacteria,

including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. The most

frequent use of aminoglycosides is empiric therapy for serious infections such as septicemia,complicated intraabdominal infections, complicated urinary tract infections, and nosocomial

respiratory tract infections. Usually, once cultures of the causal organism are grown and their

susceptibilities tested, aminoglycosides are discontinued in favor of less toxic antibiotics.[

Streptomycin was the first effective drug in the treatment of tuberculosis, though the role ofaminoglycosides such as streptomycin and amikacin has been eclipsed (because of their toxicityand inconvenient route of administration) except for multiple-drug-resistant strains.

]

Infections caused byGram-positivebacteria can also be treated with aminoglycosides, but othertypes of antibiotics are more potent and less damaging to the host. In the past, the

aminoglycosides have been used in conjunction with beta-lactam antibiotics in streptococcal

infections for their synergistic effects, in particular in endocarditis. One of the most frequentcombinations is ampicillin (a beta-lactam, or penicillin-related antibiotic) and gentamicin. Often,

hospital staff refer to this combination as "amp and gent" or more recently called "pen and gent"

for penicillin and gentamicinAminoglycosides are mostly ineffective against anaerobic bacteria,

fungi, and viruses

http://en.wikipedia.org/wiki/Aerobic_organismhttp://en.wikipedia.org/wiki/Gram-negativehttp://en.wikipedia.org/wiki/Pseudomonashttp://en.wikipedia.org/wiki/Pseudomonashttp://en.wikipedia.org/wiki/Acinetobacterhttp://en.wikipedia.org/wiki/Acinetobacterhttp://en.wikipedia.org/wiki/Enterobacterhttp://en.wikipedia.org/wiki/Enterobacterhttp://en.wikipedia.org/wiki/Mycobacteriahttp://en.wikipedia.org/wiki/Mycobacteriahttp://en.wikipedia.org/wiki/Tuberculosishttp://en.wikipedia.org/wiki/Gram-positivehttp://en.wikipedia.org/wiki/Endocarditishttp://en.wikipedia.org/wiki/Endocarditishttp://en.wikipedia.org/wiki/Gram-positivehttp://en.wikipedia.org/wiki/Tuberculosishttp://en.wikipedia.org/wiki/Mycobacteriahttp://en.wikipedia.org/wiki/Enterobacterhttp://en.wikipedia.org/wiki/Acinetobacterhttp://en.wikipedia.org/wiki/Pseudomonashttp://en.wikipedia.org/wiki/Gram-negativehttp://en.wikipedia.org/wiki/Aerobic_organism

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Nonsense suppression

The interference with DNA proofreading has been exploited to treat genetic diseases that result

from premature stop codons (leading to early termination of protein synthesis and truncatedproteins). Aminoglycosides can cause the cell to overcome the stop codons, insert a random

amino acid, and express a full-length protein.The aminoglycosidegentamicin has been used to treatcystic fibrosis (CF) cells in the laboratory

to induce them to grow full-length proteins. CF is caused by a mutation in thegene coding for

thecystic fibrosis transmembrane conductance regulator(CFTR) protein. In approximately 10%

of CF cases, the mutation in this gene causes its early termination duringtranslation,leading to

the formation of is truncated and non-functional CFTR protein. It is believed thatgentamicin

distorts the structure of the ribosome-RNA complex, leading to a mis-reading of thetermination

codon,causing theribosome to "skip" over the stop sequence and to continue with the normal

elongation and production of the CFTR protein

http://en.wikipedia.org/wiki/Stop_codonshttp://en.wikipedia.org/wiki/Gentamicinhttp://en.wikipedia.org/wiki/Cystic_fibrosishttp://en.wikipedia.org/wiki/Genehttp://en.wikipedia.org/wiki/Cystic_fibrosis_transmembrane_conductance_regulatorhttp://en.wikipedia.org/wiki/Cystic_fibrosis_transmembrane_conductance_regulatorhttp://en.wikipedia.org/wiki/Cystic_fibrosis_transmembrane_conductance_regulatorhttp://en.wikipedia.org/wiki/Translation_%28biology%29http://en.wikipedia.org/wiki/Gentamicinhttp://en.wikipedia.org/wiki/Stop_codonhttp://en.wikipedia.org/wiki/Stop_codonhttp://en.wikipedia.org/wiki/Ribosomehttp://en.wikipedia.org/wiki/Ribosomehttp://en.wikipedia.org/wiki/Stop_codonhttp://en.wikipedia.org/wiki/Stop_codonhttp://en.wikipedia.org/wiki/Gentamicinhttp://en.wikipedia.org/wiki/Translation_%28biology%29http://en.wikipedia.org/wiki/Cystic_fibrosis_transmembrane_conductance_regulatorhttp://en.wikipedia.org/wiki/Genehttp://en.wikipedia.org/wiki/Cystic_fibrosishttp://en.wikipedia.org/wiki/Gentamicinhttp://en.wikipedia.org/wiki/Stop_codons