resistencia

RESEARCH

In 1984, Carlos Amabile started exploring the effects of ascorbic acid on penicillin-resistance plasmids of Staphylococcus aureus, the so-called golden staph. We found that vitamin C, at very high concentrations --difficult to attain in human blood, even after a large vitamin intake-- can eliminate some of these plasmids or, at least, inhibit their expression, making the carrier cells slightly more sensitive to antibiotics. Carlos Amabile, Ma. Elena Wah and Rosa Ma. Piña have reported the results of this work in two papers, a book chapter, two abstracts in local congresses, and an abstract in an international congress report. In addition, this work led to a new project on the elimination of resistance plasmids initiated by Fabrizio Delissalde. A group of substances sharing the genotoxic profile of ascorbate was selected from a database. Acrolein, the first compound tested, showed effects similar to those of ascorbate when applied to staphylococcal resistant strains.
Between 1990 and 1995, we developed --in collaboration with Marina Chicurel, then at Harvard University-- a theoretical model of the role of bacterial plasmids in evolution and the spread of genes, including antibiotic resistance genes. Since then, other groups have tested several predictions from this model. A review paper in Cell, a research paper in an international journal, and an article in American Scientist, were the outcome of this project. In 1995, we initiated a collaboration with Anne Summers at the University of Georgia to study the association of antibiotic- and mercury resistance in uropathogenic bacteria. Results from this project, partially financed by the International Academy of Oral Medicine and Toxicology, were published in the proceedings of a local congress (co-authors: Pilar Rendon, Irene Fernandez and Carlos Amabile), and in a book chapter. The study of mercury resistance is still a major area of research in the lab.
After publishing a mini-review for Antimicrobial Agents and Chemotherapy in 1997, and with partial financial support from the NIH, we started a collaboration with Abigail Salyers at the University of Illinois to establish a network for monitoring antibiotic resistance in commensal bacteria, for ROAR-APUA (Reservoirs of Antibiotic Resistance, of the Alliance for the Prudent Use of Antibiotics). We assessed the resistance of oral commensal streptococci isolated from healthy Cubans and Mexicans who were not taking antibiotics. Results were published in FEMS Microbiology Letters. Javier Diaz, Alejandro Carbajal and Carlos Amabile are co-authors of this study.
	In 1999, at the Congress of the European Society for Evolutionary Biology, we presented results from sequence analyses of a bi-functional enzyme conferring resistance to nearly all aminoglycoside antibiotics. The enzyme seems to have been "assembled" in staphylococci, and then being spread by enterococci plasmids. Javier Diaz and Alejandro Carbajal performed the analyses, which included the development of a new algorithm to assess the origins of horizontally-mobilized genes.
Starting in the year 2000, Fabrizio Delissalde explored the relationship between the ability to form biofilms, and the presence of "canonical" resistance determinants among hospital strains of Pseudomonas aeruginosa. It is well known that organisms living in a biofilm are more resistant to antibiotics than "planktonic" cells, and several research teams are investigating the underlying mechanisms. But there is little knowledge regarding the relationship between biofilms and the presence of resistance genes: Initial results were published in the International Journal of Antimicrobial Agents, in 2004.

In collaboration with Irma Rosas and Valeria Souza, at the National University of Mexico, and the bioinformatics work of Javier Díaz, we started a project to know the origin and stability of integrons in Escherichia coli. Integrons are genetic elements that allow the integration and expression of other elements, known as cassettes, many of which bear antibiotic resistance genes. Integrons are common among clinical isolates, but rather rare in environmental ones. The results of this work that combines “wet” lab and in silico processes, was published in 2008 in Microbiology. Previous work with Irma Rosas’ team, on the resistance of bacterial isolates from urban dust at Mexico City, was published in the International Journal of Hygiene and Environmental Health, and was the key for a chapter in the Encyclopedia of Environmental Health, in preparation by Elsevier.

Along with José Luis Arredondo, at the National Institute of Paedriatrics, we developed several projects aimed to really know how big the resistance problem is in Mexico. Starting with a survey of respiratory tract pathogens, we then moved to bacteria causing infection in the urinary tract. Among these, we found a high prevalence of resistance toward the most common drugs used to treat these infections, but not towards nitrofurantoin, an antimicrobial compound that has been used for more than 50 years. We also explored the resistance of yeasts and moulds towards amphotericin B and several triazole drugs. Results from these projects have been published in the Journal of Infection in Developing Countries.

Joining the efforts of Irma Rosas and her team, and of José Luis Arredondo, we did some research on the prevalence of fluoroquinolone resistance in clinical and environmental E. coli isolates. We found that urinary isolates –but not enteric ones- have a high resistance prevalence, and that this is usually of a high level (tens to hundreds of micrograms per mililiter); on the other hand, isolates from a urban lake (Xochimilco) have lower prevalence of resistance, and this is of barely above the “breakpoint” used clinically. These suggest that there is an environmental selective pressure that favours low-level fluoroquinolone resistance. These results were published in the Journal of Applied Microbiology.

Along with research, a number of publications for general readership magazines and review books have been published in these years, including two pieces on antibiotic resistance for American Scientist, and 5 books published by Landes, Horizon and Springer.