Inhibition of
            <i>aac(6′)-Ib</i>
            -mediated amikacin resistance by nuclease-resistant external guide sequences in bacteria

Bistue, Alfonso J. C. Soler; Martín, Fernando A.; Vozza, Nicolás; Ha, Hongphuc; Joaquín, Jonathan C.; Zorreguieta, Ángeles; Tolmasky, Marcelo E.

doi:10.1073/pnas.0906529106

Cited by 63 publications

(66 citation statements)

References 32 publications

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“…A similar strategy could be applied to inactivate antibiotic resistance genes (156). Antisense strategies directed toward specific resistance genes (such as aac(6Ј)-Ib) have been successfully applied to reduce AbR (amikacin resistance) (125). Recently, small interfering RNAs have also been considered "therapeutic targets" for gene silencing (23,120), a concept of potential application to AbR.…”

Section: Promiscuity Inhibitors (I) Inhibitors Of Interbacterial Dismentioning

confidence: 99%

Ecology and Evolution as Targets: the Need for Novel Eco-Evo Drugs and Strategies To Fight Antibiotic Resistance

Baquero

Coque

Cruz

2011

Antimicrob Agents Chemother

167

133

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In recent years, the explosive spread of antibiotic resistance determinants among pathogenic, commensal, and environmental bacteria has reached a global dimension. Classical measures trying to contain or slow locally the progress of antibiotic resistance in patients on the basis of better antibiotic prescribing policies have clearly become insufficient at the global level. Urgent measures are needed to directly confront the processes influencing antibiotic resistance pollution in the microbiosphere. Recent interdisciplinary research indicates that new eco-evo drugs and strategies, which take ecology and evolution into account, have a promising role in resistance prevention, decontamination, and the eventual restoration of antibiotic susceptibility. This minireview summarizes what is known and what should be further investigated to find drugs and strategies aiming to counteract the "four P's," penetration, promiscuity, plasticity, and persistence of rapidly spreading bacterial clones, mobile genetic elements, or resistance genes. The term "drug" is used in this eco-evo perspective as a tool to fight resistance that is able to prevent, cure, or decrease potential damage caused by antibiotic resistance, not necessarily only at the individual level (the patient) but also at the ecological and evolutionary levels. This view offers a wealth of research opportunities for science and technology and also represents a large adaptive challenge for regulatory agencies and public health officers. Eco-evo drugs and interventions constitute a new avenue for research that might influence not only antibiotic resistance but the maintenance of a healthy interaction between humans and microbial systems in a rapidly changing biosphere.

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Section: Promiscuity Inhibitors (I) Inhibitors Of Interbacterial Dismentioning

confidence: 99%

Ecology and Evolution as Targets: the Need for Novel Eco-Evo Drugs and Strategies To Fight Antibiotic Resistance

Baquero

Coque

Cruz

2011

Antimicrob Agents Chemother

167

133

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“…These results indicate that after appropriate conditions are found, this strain could potentially be used as a model for technologies, such as antisense gene silencing, which require internalization of oligonucleotides or oligonucleotide analogs. A recent antisense study has been published using a hyperpermeable E. coli strain that was able to take up LNA/DNA oligomers (18).…”

Section: Case Reportmentioning

confidence: 99%

Naturally Competent Acinetobacter baumannii Clinical Isolate as a Convenient Model for Genetic Studies

et al. 2010

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Acinetobacter baumannii A118 was isolated from a patient's blood culture. It is susceptible to several antibiotics, is naturally competent, and supports replication and stable maintenance of four plasmid replicons. A. baumannii A118 took up a fluorophore-labeled oligonucleotide analog. These characteristics make this isolate a convenient model for genetic studies. CASE REPORTAcinetobacter baumannii A118 was isolated from a blood culture of a patient admitted to an intensive care unit in a hospital in Buenos Aires, Argentina. The isolate was identified at the species level using several criteria: (i) the biochemical scheme described by Bouvet and Grimont (1); (ii) amplified ribosomal DNA restriction analysis (ARDRA) (12,22); the restriction pattern obtained with CfoI, AluI, and MboI, which is 111, characteristic for A. baumannii (http://users.ugent.be /ϳmvaneech/ARDRA/Acinetobacter.html) (Fig. 1A); (iii) amplification and sequencing of the 16S rRNA; (iv) amplification of the rpoB gene; and (v) identification and sequencing of bla OXA-51-like, a carbapenemase gene intrinsic to A. baumannii (12,21). A. baumannii A118 lacks the integrase genes intI1, intI2, and intI3 and includes the competence genes comA, comM, and pilC, as determined by PCR amplification and DNA sequencing. Determination of antibiotic susceptibilities using the agar dilution method according to the CLSI guidelines (2) indicated that A. baumannii A118 is susceptible to ceftazidime, cefepime, piperacillin, minocycline, amikacin (Amk), gentamicin, trimethoprim-sulfamethoxazole, and ciprofloxacin. Although there is no CLSI guideline for using kanamycin (Kan) on A. baumannii, we determined the MIC, 1.5 g/ml, because this antibiotic is widely used as a selective drug in laboratory experiments.Bacteria of the genus Acinetobacter have been shown to be naturally competent (4). However, while data on natural competence of A. baylyi abound, studies of natural competence, as well as stability of plasmid replicons that could be used as potential cloning vehicles for researching A. baumannii, are scarce (13). Here we determined the competency of the A. baumannii A118 isolate and the stability of several plasmid replicons, some of them widely used as genetic tools. The plasmids pJHCMW1 (16), pMET1 (17), pAADA1KN, pAADB, and pVK102 (9) (Table 1) were used in transformation and stability assays. Plasmid DNA was isolated using the QIAfilter midi kit (Qiagen). Plasmid stability assays were carried out for 40 generations, as described previously (20). Briefly, plasmid-containing cells in late log phase were diluted 10 Ϫ6 -fold in fresh nonselective medium (LB broth) and incubated at 37°C until the culture reached the same optical density (20 generations). This culture was again diluted, and the procedure was repeated to reach 40 generations. These cultures were diluted and spread on selective and nonselective plates to determine the percentage of plasmid-containing cells. The case of pAADA1KN is discussed below. Experiments were done twice; plasmid DNA was prepared f...

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“…Other modified oligoribonucleotides that are relatively insensitive to degradative nucleases have also been developed recently (Soler Bistue et al 2009). When the basic peptide, (RXR) 4 XB, is linked to one end of a PMO, the hybrid molecule (called a PPMO) can permeate several bacterium (Mellbye et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Morpholino oligonucleotides do not participate perfectly in standard Watson-Crick complexes with RNA

Xiao

Wesolowski

Izadjoo³

et al. 2010

RNA

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RNase P from E. coli will cleave a RNA at a site designated in a complex with an external guide sequence (EGS). The location of the site is determined by the Watson-Crick complementary sequence that can be formed between the RNA and the EGS. Morpholino oligonucleotides (PMOs) that have the same base sequences as any particular EGS will not direct cleavage by RNase P of the target RNA at the expected site in three mRNAs. Instead, cleavage occurs at a secondary site that does not correspond exactly to the expected Watson-Crick sequence in the PMO. This cleavage in the mRNA for a drug resistance gene, CAT mRNA, is at least second order in the concentration of the PMOs, but the mechanism is not understood yet and might be more complicated than a simple second-order reaction. EGSs and PMOs inhibit the reactions of each other effectively in a competitive fashion. A basic peptide attached to the PMO (PPMO) is more effective because of its binding properties to the mRNA as a substrate. However, a PMO is just as efficient as a PPMO on a mRNA that is mutated so that the canonical W-C site has been altered. The altered mRNA is not recognizable by effective extensive W-C pairing to an EGS or PMO. The complex of a PMO on a mutated mRNA as a substrate shows that the dimensions of the modified oligonucleotide cannot be the same as a naked piece of single-stranded RNA.

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Inhibition of aac(6′)-Ib -mediated amikacin resistance by nuclease-resistant external guide sequences in bacteria

Cited by 63 publications

References 32 publications

Ecology and Evolution as Targets: the Need for Novel Eco-Evo Drugs and Strategies To Fight Antibiotic Resistance

Ecology and Evolution as Targets: the Need for Novel Eco-Evo Drugs and Strategies To Fight Antibiotic Resistance

Naturally Competent Acinetobacter baumannii Clinical Isolate as a Convenient Model for Genetic Studies

Morpholino oligonucleotides do not participate perfectly in standard Watson-Crick complexes with RNA

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