Structures of the Class D Carbapenemases OXA-23 and OXA-146: Mechanistic Basis of Activity against Carbapenems, Extended-Spectrum Cephalosporins, and Aztreonam

Kaitany, Kip Chumba J.; Klinger, Neil V.; June, Cynthia M.; Ramey, Maddison E.; Bonomo, Robert A.; Powers, R.A.; Leonard, David A.

doi:10.1128/aac.00762-13

Cited by 75 publications

(125 citation statements)

References 45 publications

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“…Despite the relatively low turnover rates for carbapenems displayed by these enzymes, it appears that they counter this through the presence of a "hydrophobic bridge" across the top of the active site, formed by phenylalanine 110 and methionine 221 (35), as the presence of a corresponding bridge in OXA-40 has been shown to be responsible for tight binding of the carbapenems (38,39). Recently, it was demonstrated that OXA-146 has an expanded hydrolytic spectrum that includes ceftazidime, which is not hydrolyzed by the other class D OXA-type carbapenemases, while retaining its activity against the carbapenems (35). This is the first observation of an OXA-type carbapenemase with ESBL properties, which may prove to be problematic in the future.…”

Section: Oxa-23-like ␤-Lactamasesmentioning

confidence: 99%

“…The discovery of several bla OXA-23-like genes (bla , bla , bla , bla , bla , and bla OXA-134 ) on the chromosome of Acinetobacter radioresistens isolates indicates that this species is the likely natural source of this enzyme group (30)(31)(32). Comparison of the GC con- (34)(35)(36). The kinetic properties determined vary considerably between studies, even for the same enzyme, making it difficult to make valid comparisons.…”

Section: Oxa-23-like ␤-Lactamasesmentioning

confidence: 99%

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OXA β-Lactamases

2014

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SUMMARY The OXA β-lactamases were among the earliest β-lactamases detected; however, these molecular class D β-lactamases were originally relatively rare and always plasmid mediated. They had a substrate profile limited to the penicillins, but some became able to confer resistance to cephalosporins. From the 1980s onwards, isolates of Acinetobacter baumannii that were resistant to the carbapenems emerged, manifested by plasmid-encoded β-lactamases (OXA-23, OXA-40, and OXA-58) categorized as OXA enzymes because of their sequence similarity to earlier OXA β-lactamases. It was soon found that every A. baumannii strain possessed a chromosomally encoded OXA β-lactamase (OXA-51-like), some of which could confer resistance to carbapenems when the genetic environment around the gene promoted its expression. Similarly, Acinetobacter species closely related to A. baumannii also possessed their own chromosomally encoded OXA β-lactamases; some could be transferred to A. baumannii , and they formed the basis of transferable carbapenem resistance in this species. In some cases, the carbapenem-resistant OXA β-lactamases (OXA-48) have migrated into the Enterobacteriaceae and are becoming a significant cause of carbapenem resistance. The emergence of OXA enzymes that can confer resistance to carbapenems, particularly in A. baumannii , has transformed these β-lactamases from a minor hindrance into a major problem set to demote the clinical efficacy of the carbapenems.

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Section: Oxa-23-like ␤-Lactamasesmentioning

confidence: 99%

Section: Oxa-23-like ␤-Lactamasesmentioning

confidence: 99%

OXA β-Lactamases

2014

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“…This pathogen has many kinds of innate and acquired mechanisms for antibiotic resistance such as change of target site, over production of efflux pumps, low permeability of outer membrane, and inactivation of enzymes like β-lactamases (4). (6). These enzymes are classified into four main OXA subfamilies: OXA-23-like, OXA-24/40-like, OXA-58-like, and OXA-51-like that the latest one is chromosomally located in all A. baumannii strains.…”

Section: Introductionmentioning

confidence: 99%

Identification and Isolation of Insertion Sequences, in Carbapenem Resistant Clinical Isolates of Acinetobacter baumannii from Tehran Hospitals

Owrang

Fallah²,

Irani

et al. 2017

Jundishapur J Microbiol

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Background: Identification of real agents inducing antibiotic resistance in Acinetobacter baumannii can help us control and prevent the infections and reduce the mortality rates caused by this microorganism. Objectives: The purpose of this study was to identify the insertion elements that can play important roles in antibiotic resistance in A. baumannii.Methods: A total of 105 A. baumannii isolates from clinical samples were tested for their susceptibility to different antibiotics using disc diffusion test (DDT). Then, the isolates were evaluated for the presence of blaOXA genes along with IS elements by polymerase chain reaction (PCR). Results: PCR analysis showed that ISAba1 was present in all the isolates while 92.36% of the isolates were positive for ISAba2. All the strains of A. baumannii possessed a blaOXA-51-like gene but blaOXA-58-like gene was absent in all of them. About 64.76% of the isolates were positive for blaOXA-24-like gene and 98.09% were positive for blaOXA-23-like gene. All of the isolates were pandrug resistant A. baumannii and the lowest resistance rates were observed toward minocycline and amikacin (93.33% in both) and trimethoprim/sulfamethoxazole (92.38%). Conclusions:The high prevalence rates of ISAba1 and ISAba2 among A. baumannii isolates can explain the rapid dissemination of resistance genes. Thus, finding the accessory genes such as IS elements, which can affect antibiotic resistance, should be more considered.

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“…The amino acid sequences of OXA-23 were aligned using CLUSTALW as implemented in MEGA 6 [11]. As shown in the alignment results (Figure 1), four mutations of OXA-23 were detected.…”

mentioning

confidence: 99%

“…ZZAB31, OXA-49 and OXA-146 were distributed into one cluster, since they all had the same added residue (A220). Positive selection using blaOXA-23 sequences files was identified by Hyphy selection test [11], but no specific position was positively selected.…”

mentioning

confidence: 99%