Characterization of transposon Tn1528, which confers amikacin resistance by synthesis of aminoglycoside 3'-O-phosphotransferase type VI

Lambert, Thierry; Gerbaud, Guy; Courvalin, Patrice

doi:10.1128/aac.38.4.702

Cited by 19 publications

(13 citation statements)

References 32 publications

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“…APH(3=) is the most widespread phosphotransferase group among clinical pathogens, but the variant APH(3=)-VI was described in only a few Enterobacteriaceae and Acinetobacter species isolates (30)(31)(32). The APH(3=)-VI variants usually confer resistance to most aminoglycosides, including kanamycin, amikacin, neomycin, paromomycin, ribostamycin, butirosin, and isepamicin (33).…”

Section: Discussionmentioning

confidence: 99%

Characterization of BKC-1 Class A Carbapenemase from Klebsiella pneumoniae Clinical Isolates in Brazil

Nicoletti

Marcondes

Martins

et al. 2015

Antimicrob Agents Chemother

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Three Klebsiella pneumoniae clinical isolates demonstrating carbapenem resistance were recovered from different patients hospitalized at two medical centers in São Paulo, Brazil. Resistance to all ␤-lactams, quinolones, and some aminoglycosides was observed for these isolates that were susceptible to polymyxin B. Carbapenem hydrolysis, which was inhibited by clavulanic acid, was observed for all K. pneumoniae isolates that belonged to the same pulsed-field gel electrophoresis (PFGE) type and a novel sequence type (ST), ST1781 (clonal complex 442 [CC442]). A 10-kb nonconjugative incompatibility group Q (IncQ) plasmid, denominated p60136, was transferred to Escherichia coli strain TOP10 cells by electroporation. The full sequencing of p60136 showed that it was composed of a mobilization system, ISKpn23, the phosphotransferase aph3A-VI, and a 941-bp open reading frame (ORF) that codified a 313-amino acid protein. This ORF was named bla BKC-1 . Brazilian Klebsiella carbapenemase-1 (BKC-1) showed a pI of 6.0 and possessed the highest identity (63%) with a ␤-lactamase of Sinorhizobium meliloti, an environmental bacterium. Hydrolysis studies demonstrated that purified BKC-1 not only hydrolyzed carbapenems but also penicillins, cephalosporins, and monobactams. However, the carbapenems were less efficiently hydrolyzed due to their very low k cat values (0.0016 to 0.031 s ؊1 ). In fact, oxacillin was the best substrate for BKC-1 (k cat /K m , 53,522.6 mM ؊1 s ؊1 ). Here, we report a new class A carbapenemase, confirming the diversity and rapid evolution of ␤-lactamases in K. pneumoniae clinical isolates.

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Section: Discussionmentioning

confidence: 99%

Characterization of BKC-1 Class A Carbapenemase from Klebsiella pneumoniae Clinical Isolates in Brazil

Nicoletti

Marcondes

Martins

et al. 2015

Antimicrob Agents Chemother

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“…A recent report (144) of plasmid-encoded amikacin resistance in clinical strains of P. aeruginosa may also reflect mobilization of an aac(6Ј) gene on, e.g., a transposon or integron. In one report, too, the aph(3Ј)-VIa gene of the highly amikacin-resistant strain being studied was present on a transposon (82). As with other aminoglycoside-modifying enzymes, genes for ANT enzymes can be integron associated, particularly the aadAencoded ANT(3Љ) (9) enzyme that inactivates streptomycin and spectinomycin and that is commonplace on class 1 integrons (72,73,109,143,151,162); but they can also be encoded by aadB, i.e., ANT(2Љ)-I (18) and, possibly, ANT(4Ј)-IIb (132).…”

Section: Modifying Enzymesmentioning

confidence: 99%

“…HpaA activation of these genes is stimulated by 4-HPA, suggesting that the phosphotransferase may, in fact, play an intended role in metabolism and only fortuitously provides resistance to aminoglycosides. APH(3Ј) enzymes that provide resistance to other aminoglycosides have also been described in P. aeruginosa and include APH(3Ј)-VI (amikacin and isepamicin) (74,82,99,156) and APH(2Љ) (gentamicin and tobramycin) (74). ANTs.…”

Section: Modifying Enzymesmentioning

confidence: 99%

Aminoglycoside Resistance inPseudomonas aeruginosa

Poole

2005

Antimicrob Agents Chemother

411

322

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“…As in other bacterial species, multidrug resistance can be achieved by two mechanisms: (i) horizontal transfer of genetic information and (ii) mutation of endogenous genes. Acquired resistance determinants that are carried by plasmids (18,28), transposons (23,29), and integrons (33,43) have been described for Acinetobacter spp. Determination of the genomic sequence of several A. baumannii strains has improved our knowledge of the ways in which A. baumannii can develop antibiotic resistance (1,21,38,45).…”

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confidence: 99%

Screening and Quantification of the Expression of Antibiotic Resistance Genes in Acinetobacter baumannii with a Microarray

Coyne

Guigon²,

Courvalin

et al. 2010

Antimicrob Agents Chemother

112

113

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An oligonucleotide-based DNA microarray was developed to evaluate expression of genes for efflux pumps in Acinetobacter baumannii and to detect acquired antibiotic resistance determinants. The microarray contained probes for 205 genes, including those for 47 efflux systems, 55 resistance determinants, and 35 housekeeping genes. The microarray was validated by comparative analysis of mutants overexpressing or deficient in the pumps relative to the parental strain. The performance of the microarray was also evaluated using in vitro single-step mutants obtained on various antibiotics. Overexpression, confirmed by quantitative reverse transcriptase PCR, of RND efflux pumps AdeABC, due to a G30D substitution in AdeS in a multidrug-resistant (MDR) strain obtained on gentamicin, and AdeIJK, in two mutants obtained on cefotaxime or tetracycline, was detected. A new efflux pump, AdeFGH, was found to be overexpressed in a mutant obtained on chloramphenicol. Study of MDR clinical isolates, including the AYE strain, whose entire sequence has been determined, indicated overexpression of AdeABC and of the chromosomally encoded cephalosporinase as well as the presence of several acquired resistance genes. The overexpressed and acquired determinants detected by the microarray could account for nearly the entire MDR phenotype of the isolates. The microarray is potentially useful for detection of resistance in A. baumannii and should allow detection of new efflux systems associated with antibiotic resistance.Multidrug-resistant (MDR) strains of Acinetobacter baumannii have emerged in recent decades. This opportunistic pathogen is responsible for severe infections, particularly hospital-acquired pneumonia and bloodstream, urinary tract, and wound infections, and has become of worldwide concern (13). As in other bacterial species, multidrug resistance can be achieved by two mechanisms: (i) horizontal transfer of genetic information and (ii) mutation of endogenous genes. Acquired resistance determinants that are carried by plasmids (18, 28), transposons (23,29), and integrons (33, 43) have been described for Acinetobacter spp. Determination of the genomic sequence of several A. baumannii strains has improved our knowledge of the ways in which A. baumannii can develop antibiotic resistance (1,21,38,45). An 86-kb resistance island, AbaR1, found in strain AYE, contains as many as 25 antibiotic and 20 antiseptic and heavy metal resistance genes (16). Variants of this island are integrated at the same chromosomal locus in a significantly high proportion of MDR strains (37). In addition to these acquired resistance genetic elements, alterations in endogenous functions are involved in resistance, such as overexpression of chromosomally encoded ␤-lactamases ADC and OXA-51-like; loss of porins CarO and Omp33-36 contributing to carbapenem resistance; mutation in the GyrA and ParC fluoroquinolone targets; and overexpression of efflux systems (13).Efflux systems are components of the bacterial membrane that are thought to play a role in homeost...

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Characterization of transposon Tn1528, which confers amikacin resistance by synthesis of aminoglycoside 3'-O-phosphotransferase type VI

Cited by 19 publications

References 32 publications

Characterization of BKC-1 Class A Carbapenemase from Klebsiella pneumoniae Clinical Isolates in Brazil

Characterization of BKC-1 Class A Carbapenemase from Klebsiella pneumoniae Clinical Isolates in Brazil

Aminoglycoside Resistance inPseudomonas aeruginosa

Screening and Quantification of the Expression of Antibiotic Resistance Genes in Acinetobacter baumannii with a Microarray

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