Dr. Angeles Zorreguieta
Instituto Fundación Leloir
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Antibiotic resistance
Drug resistant bacteria are commonly isolated from healthy persons as well as from patients with community-acquired infections in developing countries (2). Furthermore isolation of multiresistant strains from intrahospitalary infections have become the norm rather than the exception (5). This is due to a number of factors that include but are not limited to the high incidence of infectious disease, excessive clinical use of antibiotics (a problem also in industrialized countries), and their misuse by the public (in many developing countries antibiotics can be purchased without prescription). The problem is serious because as antibiotic resistance is making existing treatments less effective, development of new antibiotics is slowing down (1).
We are working to characterize mechanisms of dissemination of genes coding for antibiotic resistance and to develop strategies to extend the life of existing antibiotics.
A number of diseases that disproportionately affect some populations are known to weaken the immune system increasing the susceptibility to bacterial infections. The rise of antibiotic resistance complicates their treatment.
Dissemination of genes coding for antibiotic resistance: we have recently characterized an integron that harbors clinically relevant resistance genes such as blaCTX-M -2, which codes for CTX-M-2, an extended-spectrum beta-lactamase from the growing family enzymes that preferentially hydrolyze cefotaxime over ceftazidime; and aac(6’)-Ib, a gene encoding resistance to several important aminoglycoside antibiotics. This integron has been found associated to transposition genes making it potentially mobile (4).
Extending the life of antibiotics: development of inhibitors of enzymes that degrade antibiotics has been very useful to extend the life of these drugs. For example, clavulanic acid, a beta-lactamase inhibitor produced from Streptomyces clavuligerus, extends the activity of certain beta-lactam antibiotics against bacteria which owe their resistance to the production of beta-lactamases (3). We are developing strategies to interfere with expression of enzymes that confer resistance to non-beta-lactam antibiotics.
1. 2005. Shadow epidemics - The growing menace of drug resistance. Alliance for the Prudent Use of Antibiotics.
2. Kunin, C. M. 1993. Resistance to antimicrobial drugs - a worldwide calamity. Ann Intern Med 118:557-561.
3. Paterson, D. L., and R. A. Bonomo. 2005. Extended-spectrum beta-lactamases: a clinical update. Clin Microbiol Rev 18:657-86.
4. Soler Bistue, A. J., F. A. Martin, A. Petroni, D. Faccone, M. Galas, M. E. Tolmasky, and A. Zorreguieta. 2006. Vibrio cholerae InV117, a Class 1 Integron Harboring aac(6')-Ib and blaCTX-M-2, Is Linked to Transposition Genes. Antimicrob Agents Chemother 50:1903-7.
5. Woloj, M., M. E. Tolmasky, M. C. Roberts, and J. H. Crosa. 1986. Plasmid-encoded amikacin resistance in multiresistant strains of Klebsiella pneumoniae isolated from neonates with meningitis. Antimicrob Agents Chemother 29:315-9.
