A mechanism of carbapenem resistance due to a new insertion element (ISPa133) in Pseudomonas aeruginosa Authors Lidia Ruiz-Martínez Lidia López-Jiménez Valeria d’Ostuni, Ester Fusté Teresa Vinuesa Miguel Viñas Keywords: Pseudomonas aeruginosa, protein OprD, carbapenems, imipenem, insertion elements, antimicrobial resistance Abstract This study explored the evolutionary mechanism by which the clinical isolate PA110514 yields the imipenemresistantderivative PA116136. Both isolates were examined by PFGE and SDS-PAGE, which led to the identification of a new insertion sequence, ISPa133. This element was shown to have distinct chromosomal locations in each of the original isolatesthat appeared to explain the differences in imipenem susceptibilty. In strain PA110514, ISPa133 is located 56 nucleotides upstream of the translational start codon, which has no effect on expression of the porin OprD. However, in strain PA116136 ISPa133 it is located in front of nucleotide 696 and, by interrupting the coding region, causes a loss of OprD expression, thus conferring imipenem resistance. In vitro experiments mimicking the natural conditions of selective pressure yielded imipenem- resistant strains in which ISPa133 similarly interrupted oprD. Amechanism is proposed whereby ISPa133 acts as a mobile switch, with its position in oprD depending on the degree of selective pressure exerted by imipenem. [Int Microbiol 2011; 14(1):51-58] Author Biography Ester Fusté Downloads PDF Issue Vol. 14 No. 1 (2011) Section Research Articles License Submission of a manuscript to International Microbiology implies: that the work described has not been published before, including publication in the World Wide Web (except in the form of an Abstract or as part of a published lecture, review, or thesis); that it is not under consideration for publication elsewhere; that all the coauthors have agreed to its publication. The corresponding author signs for and accepts responsability for releasing this material and will act on behalf of any and all coauthors regarding the editorial review and publication process.If an article is accepted for publication in International Microbiology, the authors (or other copyright holder) must transfer to the journal the right–not exclusive–to reproduce and distribute the article including reprints, translations, photographic reproductions, microform, electronic form (offline, online) or any other reproductions of similar nature. Nevertheless, all article in International Microbiology will be available on the Internet to any reader at no cost. The journal allows users to freely download, copy, print, distribute, search, and link to the full text of any article, provided the authorship and source of the published article is cited. The copyright owner's consent does not include copying for new works, or resale. In these cases, the specific written permission of International Microbiology must first be obtained.Authors are requested to create a link to the published article on the journal's website. The link must be accompanied by the following text: "The original publication is available on LINK at <http://www.im.microbios.org>. Please use the appropiate URL for the article in LINK. Articles disseminated via LINK are indexed, abstracted, and referenced by many abstracting and information services, bibliographic networks, subscription agencies, library networks, and consortia.