The spread of antibiotic resistances and the appearance of multiple-antibiotic-resistant pathogenic bacteria has been recognized by the WHO as a serious problem that complicates medical treatment of bacterial infections. WHO has called for urgent measures to fight against the spread of pathogenic strains that are resistant to several antibiotics. These measures concern appropriate antibiotic therapy, hospital hygiene, control of bacterial infections and the extension of existing surveillance systems to an international network in order to collect epidemiological information on antimicrobial resistance. Recent reports have also shown a marked and worrying increase of antibiotic resistance in food-poisoning bacteria due to non-rational and excessive uses of antibiotics as therapeutic agent or as growth promotor in livestock.
Another aspect of the antibiotic resistance issue is the uses of antibiotic resistance genes as selection marker in genetically modified organisms (GMOs). The main safety concern relates to the escape or transfer of the antibiotic resistance genes to sensitive bacterial strains when these GMO are introduced into the environment.
In order to help regulators or applicants to carry out risk assessment of GMO containing an antibiotic resistance gene, information is provided on the genetic determinants encoding resistance and on their clinical / environmental distribution when possible. These WEB pages also gather useful links to sites monitoring antimicrobial resistances and describing the antibiotic drugs.

ANTIBIOTIC RESISTANCE MECHANISMS

Antibiotic resistance can be categorized in three types:

1. Natural or intrinsic resistance

• Inaccessibility of the target (i.e. impermeability resistance due to the absence of an adequate transporter: aminoglycoside resistance in strict anaerobes)
• Multidrug efflux systems: i.e. AcrE in E. coli, MexB in P. aeruginosa
• Drug inactivation: i.e. AmpC cephalosporinase in Klebsiella

2. Mutational resistance

• Target site modification (i.e. Streptomycin resistance: mutations in rDNA genes (rpsL), ß-lactam resistance: change in PBPs (penicillin binding proteins))
• Reduced permeability or uptake
• Metabolic by-pass (i.e trimethoprim resistance: overproduction of DHF (dihydrofolate) reductase or thi^- mutants in S. aureus)
• Derepression of multidrug efflux systems

3. Extrachromosomal or acquired resistance (Disseminated by plasmids or transposons)

• Drug inactivation (i.e. aminoglycoside-modifying enzymes, ß-lactamases, chloramphenicol acetyltransferase)
• Efflux system (i.e. tetracycline efflux)
• Target site modification (i.e. methylation in the 23S component of the 50S ribosomal subunit: Erm methylases)
• Metabolic by-pass (i.e trimethoprim resistance: resistant DHF reductase)

DESCRIPTION OF THE RESISTANCE MECHANISMS TO

ß-lactams
Aminoglycosides
Tetracyclines

(other categories include: Macrolides-lincosamides-streptogramins, Glycopeptides, Chloramphenicol, Rifampicin, Quinolones, Sulfonamides, Trimethoprim, and Nalidixic acid)