Glimpse into the genome sequence of a multidrug-resistant Acinetobacter pittii ST950 clinical isolate carrying the blaOXA-72 and blaOXA-533 genes in China

Ruan, Zhi; Chen, Yan; Wang, Jianfeng

doi:10.1590/0074-02760170019

Cited by 2 publications

(1 citation statement)

References 21 publications

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“…This recombination system is exploited by mobile DNA elements to integrate into the host genome (Midonet and Barre, 2014). A similar genetic context was also reported for other A. pittii isolates, in which the resistance gene was flanked by XerC/XerD-like recombinase sites (Cayo et al, 2014;Ruan et al, 2017;Brasiliense et al, 2019). This suggests that A. pittii may be an important source of resistance genes and contribute to their dissemination among species.…”

Section: Discussionsupporting

confidence: 59%

Phenotypic Variation and Carbapenem Resistance Potential in OXA-499-Producing Acinetobacter pittii

Zhang

Han

et al. 2020

Front. Microbiol.

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Acinetobacter pittii is increasingly recognized as a clinically important species. Here, we identified a carbapenem-non-resistant A. pittii clinical isolate, A1254, harboring bla OXA−499 , bla OXA−826 , and bla ADC−221. The bla OXA−499 genetic environment in A1254 was identical to that of another OXA-499-producing, but carbapenem-resistant, A. pittii isolate, YMC2010/8/T346, indicating the existence of phenotypic variation among OXA-499-producing A. pittii strains. Under imipenem-selective pressure, the A1254 isolate developed resistance to carbapenems in 60 generations. Two carbapenem-resistant mutants (CAB009 and CAB010) with mutations in the bla OXA−499 promoter region were isolated from two independently evolved populations (CAB001 and CAB004). The CAB009 mutant, with a mutation at position −14 (A to G), exhibited a four-fold higher carbapenem minimum inhibitory concentration (MIC) and a 4.53 ± 0.19 log 2 fold change higher expression level of bla OXA−499 than the ancestor strain, A1254. The other mutant, CAB010, with a mutation at position −42 (G to A), showed a twofold higher carbapenem MIC and a 1.65 ± 0.25 log 2 fold change higher bla OXA−499 expression level than the ancestor strain. The bla OXA−499 gene and its promoter region were amplified from the wild-type strain and two mutant isolates and then individually cloned into the pYMAb2-Hyg r vector and expressed in Acinetobacter baumannii ATCC 17978, A. pittii LMG 1035, and A. pittii A1254. All the transformed strains were resistant to carbapenem, irrespective of whether they harbored the initial or an evolved promoter sequence, and transformed strains expressing the promoter from the most resistant mutant, CAB009, showed the highest carbapenem MICs, with values of 32-64 µg/ml for imipenem and 128 µg/ml for meropenem. RNA sequencing was performed to confirm the contribution of bla OXA−499 to the development of carbapenem resistance. Although the CAB009 and CAB010 transcriptional patterns were different, bla OXA−499 was the only differentially expressed gene shared by the two mutants.

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Section: Discussionsupporting

confidence: 59%

Phenotypic Variation and Carbapenem Resistance Potential in OXA-499-Producing Acinetobacter pittii

Zhang

Han

et al. 2020

Front. Microbiol.

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Characterization of the novel OXA-213-like β-lactamase OXA-822 from Acinetobacter calcoaceticus

Tietgen

Leukert

Sommer

et al. 2020

Journal of Antimicrobial Chemotherapy

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Objectives This study analysed the novel carbapenem-hydrolysing class D β-lactamase OXA-822 identified in the clinical Acinetobacter calcoaceticus isolate AC_2117. Methods WGS was employed for identification of β-lactamases. Micro-broth dilution was used for evaluation of antibiotic susceptibility of AC_2117 and transformants containing blaOXA-822. After heterologous purification of OXA-822, OXA-359 and OXA-213, enzyme kinetics were determined using spectrometry. The effect of OXA-822 upon meropenem treatment was analysed in the Galleria mellonella in vivo infection model. Results OXA-822 is a member of the intrinsic OXA-213-like family found in A. calcoaceticus and Acinetobacter pittii. Amino acid sequence similarity to the nearest related OXA-359 was 97%. Production of OXA-822, OXA-359 and OXA-213 in Acinetobacter baumannii ATCC® 19606T resulted in elevated MICs for carbapenems (up to 16-fold). Penicillinase activity of the purified OXA-822 revealed high KM values, in the millimolar range, combined with high turnover numbers. OXA-822 showed the highest affinity to carbapenems, but affinity to imipenem was ∼10-fold lower compared with other carbapenems. Molecular modelling revealed that imipenem does not interact with a negatively charged side chain of OXA-822, as doripenem does, leading to the lower affinity. Presence of OXA-822 decreased survival of infected Galleria mellonella larvae after treatment with meropenem. Only 52.7% ± 7.7% of the larvae survived after 24 h compared with 90.9% ± 3.7% survival in the control group. Conclusions The novel OXA-822 from a clinical A. calcoaceticus isolate displayed penicillinase and carbapenemase activity in vitro, elevated MICs in different species and decreased carbapenem susceptibility in A. baumannii in vivo.

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Glimpse into the genome sequence of a multidrug-resistant Acinetobacter pittii ST950 clinical isolate carrying the blaOXA-72 and blaOXA-533 genes in China

Cited by 2 publications

References 21 publications

Phenotypic Variation and Carbapenem Resistance Potential in OXA-499-Producing Acinetobacter pittii

Phenotypic Variation and Carbapenem Resistance Potential in OXA-499-Producing Acinetobacter pittii

Characterization of the novel OXA-213-like β-lactamase OXA-822 from Acinetobacter calcoaceticus

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