Emergence of a ST248Pasteur-ST1068Oxford Carbapenem Resistance Acinetobacter pittii Clinical Isolate in China, Co-Harboring OXA-58 and OXA-500 Carbapenemases.
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ABSTRACT:
SUBMITTER: Tian C
PROVIDER: S-EPMC10474855 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
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Emergence of a ST248<sub>Pasteur</sub>-ST1068<sub>Oxford</sub> Carbapenem Resistance <i>Acinetobacter pittii</i> Clinical Isolate in China, Co-Harboring OXA-58 and OXA-500 Carbapenemases.
Tian Chongmei C Song Jianqin J Huang Delian D Wang Siwei S Zhao Yaping Y Fu Liping L Fan Xueyu X Ma Tianhong T Bai Yongfeng Y
Infection and drug resistance 20230829
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Project description:BackgroundCarbapenem-Resistant Enterobacterales (CRE) has been categorized as pathogens of critical priority by World Health organization (WHO) as they pose significant threat to global public health. Carbapenemase production considered as the principal resistance mechanism against carbapenems and with the recent surge and expansion of carbapenemases and its variants among clinically significant bacteria in India, the present study reports expansion blaOXA-78 and blaOXA-58 of in CRE of clinical origin.MethodsBacterial isolates were collected from a tertiary referral hospital and identified through VITEK® 2 Compact automated System (Biomerieux, France). Rapidec® Carba NP (Biomerieux, France) was used to investigate carbapenemase production followed by antibiotic susceptibility testing through Kirby-Bauer Disc Diffusion method and agar dilution method. Class D carbapenemase genes were targeted through PCR assay followed by investigation of horizontal transmission of blaOXA-58 and blaOXA-78. Whole genome sequencing was carried out using Illumina platform to investigate the genetic context of blaOXA-58 and blaOXA-78 genes and further characterization of the CRE isolates.ResultsThe carbapenem-resistant Escherichia coli (BJD_EC456) and Serratia marcescens (BJD_SM81) received during the study from the tertiary referral hospital were isolated from sputum and blood samples respectively. PCR assay followed by whole genome sequencing revealed that the isolates co-harbor blaOXA-58 and blaOXA-78, a variant of blaOXA-51. Horizontal transfer of blaOXA-58 and blaOXA-78 genes were unsuccessful as these genes were located on the chromosome of the study isolates. Transposon Tn6080 was linked to blaOXA-78 in the upstream region while the insertion sequences ISAba26 and ISCfr1 were identified in the upstream and downstream region of blaOXA-58 gene respectively. In addition, both the isolates were co-harboring multiple antibiotic resistance genes conferring clinical resistance towards beta-lactams, aminoglycosides, fluroquinolones, sulphonamides, tetracyclines. BJD_EC180 belonged to ST2437 while BJD_SM81 was of an unknown sequence type. The nucleotide sequences of blaOXA-78 (OQ533021) and blaOXA-58 (OQ533022) have been deposited in GenBank.ConclusionsThe study provides a local epidemiological information regarding carbapenem resistance aided by transposon and insertion sequences associated blaOXA-78 and blaOXA-58 genes associated and warrants continuous monitoring to prevent their further dissemination into carbapenem non-susceptible strains thereby contributing to carbapenem resistance burden which is currently a global concern.
| S-EPMC10486080 | biostudies-literature
Project description:ObjectiveTo characterize one KL38-OCL6-ST220 carbapenem-resistant Acinetobacter pittii strain, co-producing chromosomal NDM-1 and OXA-820 carbapenemases.MethodsA. pittii TCM strain was isolated from a bloodstream infection (BSI). Antimicrobial susceptibility tests were conducted via disc diffusion and broth microdilution. Stability experiments of bla NDM-1 and bla OXA-820 carbapenemase genes were further performed. Whole-genome sequencing (WGS) was performed on the Illumina and Oxford Nanopore platforms. Multilocus sequence typing (MLST) was analyzed based on the Pasteur and Oxford schemes. Resistance genes, virulence factors, and insertion sequences (ISs) were identified with ABRicate based on ResFinder 4.0, virulence factor database (VFDB), and ISfinder. Capsular polysaccharide (KL), lipooligosaccharide outer core (OCL), and plasmid reconstruction were tested using Kaptive and PLACNETw. PHASTER was used to predict prophage regions. A comparative genomics analysis of all ST220 A. pittii strains from the public database was carried out. Point mutations, average nucleotide identity (ANI), DNA-DNA hybridization (DDH) distances, and pan-genome analysis were performed.ResultsA. pittii TCM was ST220Pas and ST1818Oxf with KL38 and OCL6, respectively. It was resistant to imipenem, meropenem, and ciprofloxacin but still susceptible to amikacin, colistin, and tigecycline. WGS revealed that A. pittii TCM contained one circular chromosome and four plasmids. The Tn125 composite transposon, including bla NDM-1, was located in the chromosome with 3-bp target site duplications (TSDs). Many virulence factors and the bla OXA-820 carbapenemase gene were also identified. The stability assays revealed that bla NDM-1 and bla OXA-820 were stabilized by passage in an antibiotic-free medium. Moreover, 12 prophage regions were identified in the chromosome. Phylogenetic analysis showed that there are 11 ST220 A. pittii strains, and one collected from Anhui, China was closely related. All ST220 A. pittii strains presented high ANI and DDH values; they ranged from 99.85% to 100% for ANI and from 97.4% to 99.9% for DDH. Pan-genome analysis revealed 3,200 core genes, 0 soft core genes, 1,571 shell genes, and 933 cloud genes among the 11 ST220 A. pittii strains.ConclusionsThe coexistence of chromosomal NDM-1 and OXA-820 carbapenemases in A. pittii presents a huge challenge in healthcare settings. Increased surveillance of this species in hospital and community settings is urgently needed.
| S-EPMC9411868 | biostudies-literature
Project description:The basis of the beta-lactam resistance of 39 multidrug-resistant Acinetobacter baumannii isolates recovered from hospitalized patients was studied. These isolates were collected from 2001 to 2005 at the Sahloul Hospital in Sousse, Tunisia. They belonged to two distinct clones. One clone that grouped 19 isolates produced a carbapenem-hydrolyzing oxacillinase, OXA-97, that differed from OXA-58 by a single amino acid substitution and conferred the same beta-lactam resistance profile as OXA-58. The bla(OXA-97) gene was located on plasmids that varied in size in 18 isolates and was chromosomally located in a single isolate. Cloning and sequencing identified genetic structures surrounding the bla(OXA-97) gene similar to those reported to be adjacent to the bla(OXA-58) gene. In addition, the novel ISAba8 element (which is of the IS21 family) was identified. This is the first report of the nosocomial spread of carbapenemase producers in A. baumannii isolates in Africa.
| S-EPMC2346634 | biostudies-literature
Project description: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 log2 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 two-fold higher carbapenem MIC and a 1.65 ± 0.25 log2 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. Our results indicate that carbapenem-non-resistant Acinetobacter spp. strains carrying bla OXA genes have the potential to develop carbapenem resistance and need to be further investigated and monitored to prevent treatment failure due to the development of resistance.
| S-EPMC7296048 | biostudies-literature
Project description:ObjectivesAcinetobacter pittii has become an emerging opportunistic noscomial pathogen worldwide with multi-drug resistance. In the present study, an A. pittii strain was isolated from bronchoalveolar lavage fluid sample harboring both OXA-58 and NDM-1carbapenemase producing genes. The mechanisms of carbapenem resistance of the A. pittii strain was investigated.Materials and methodsCarbapenemase producing genes were examined by PCR and DNA sequencing. S1-PFGE was used to localize carbapenemase encoding genes. Filter mating and electrotransformation were used to investigate the transferability of such carbapenemase encoding genes between different strains. Genetic surroundings of bla OXA-58 and bla NDM-1 genes were detected as well.ResultsThe A. pittii strain, carrying both OXA-58 and NDM-1 carbapenemase encoding genes, was resistant to all β-lactam antibiotics, while suscepitible to ciprofloxacin, levofloxacin, tobramycin, cotrimoxazole and tigecycline. Southern blot hybridization for the bla OXA-58 and bla NDM-1 gene indicated that the two genes locate in the same plasmid with molecular weight of 310.1-336.5kb. Bla OXA-58 was located in an ISAba3-bla OXA-58-ISAba3-like structure, and the blaNDM-1 gene cluster was embedded in an ISAba125-aphA6- bla NDM-1 -ble MBL -ΔtrpF-dsbC-cutA structure sequentially.ConclusionIn the present study, it is first reported an A. pittii clincal strain in China, co-harboring OXA-58 and NDM-1 carbapenemase producing genes residing on a same plasmid. In hospital and community settings, it is of great significance and urgence to increase the surveillance of these kinds of organisms.
| S-EPMC6437464 | biostudies-literature
Project description: Not available
| S-EPMC6535544 | biostudies-literature
Project description:This study aimed at the characterization of carbapenem-resistant Klebsiella pneumoniae isolates focusing on typing of the blaOXA-48-like genes. Additionally, the correlation between the resistance pattern and biofilm formation capacity of the carbapenem-resistant K. pneumoniae isolates was studied. The collected isolates were assessed for their antimicrobial resistance and carbapenemases production by a modified Hodge test and inhibitor-based tests. The carbapenemases encoding genes (blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA-48-like) were detected by PCR. Isolates harboring blaOXA-48-like genes were genotyped by Enterobacterial Repetitive Intergenic Consensus-Polymerase Chain Reaction (ERIC-PCR) and plasmid profile analysis. The discriminatory power of the three typing methods (antibiogram, ERIC-PCR, and plasmid profile analysis) was compared by calculation of Simpson's Diversity Index (SDI). The transferability of blaOXA-48 gene was tested by chemical transformation. The biofilm formation capacity and the prevalence of the genes encoding the fimbrial adhesins (fimH-1 and mrkD) were investigated. The isolates showed remarkable resistance to β-lactams and non-β-lactams antimicrobials. The coexistence of the investigated carbapenemases encoding genes was prevalent except for only 15 isolates. The plasmid profile analysis had the highest discriminatory power (SDI = 0.98) in comparison with ERIC-PCR (SDI = 0.89) and antibiogram (SDI = 0.78). The transferability of blaOXA-48 gene was unsuccessful. All isolates were biofilm formers with the absence of a significant correlation between the biofilm formation capacity and resistance profile. The genes fimH-1 and mrkD were prevalent among the isolates. The prevalence of carbapenemases encoding genes, especially blaOXA-48-like genes in Egyptian healthcare settings, is worrisome and necessitates further strict dissemination control measures.
| S-EPMC7760040 | biostudies-literature
Project description:OXA-58 is a recently described carbapenemase from Acinetobacter spp. in Europe. We examined earlier worldwide Acinetobacter collections and found bla(OXA-58) in 30 carbapenem-nonsusceptible isolates, including several isolates collected in Argentina and Kuwait in 1995 and 1996 and in a British outbreak strain from 2000. Most isolates (28 of 30) also had bla(OXA-51). We conclude that bla(OXA-58) is geographically widespread and has occurred in Acinetobacter spp. for over 10 years.
| S-EPMC1366923 | biostudies-literature
Project description:In Enterobacterales, the most common carbapenemases are Ambler's class A (KPC-like), class B (NDM-, VIM- or IMP-like) or class D (OXA-48-like) enzymes. This study describes the characterization of twenty-four OXA-23 or OXA-58 producing-Proteus mirabilis isolates recovered from human and veterinary samples from France and Belgium. Twenty-two P. mirabilis isolates producing either OXA-23 (n = 21) or OXA-58 (n = 1), collected between 2013 and 2018, as well as 2 reference strains isolated in 1996 and 2015 were fully sequenced. Phylogenetic analysis revealed that 22 of the 24 isolates, including the isolate from 1996, belonged to a single lineage that has disseminated in humans and animals over a long period of time. The blaOXA-23 gene was located on the chromosome and was part of a composite transposon, Tn6703, bracketed by two copies of IS15∆II. Sequencing using Pacbio long read technology of OXA-23-producing P. mirabilis VAC allowed the assembly of a 55.5-kb structure encompassing the blaOXA-23 gene in that isolate. By contrast to the blaOXA-23 genes, the blaOXA-58 gene of P. mirabilis CNR20130297 was identified on a 6-kb plasmid. The acquisition of the blaOXA-58 gene on this plasmid involved XerC-XerD recombinases. Our results suggest that a major clone of OXA-23-producing P. mirabilis is circulating in France and Belgium since 1996.
| S-EPMC7280188 | biostudies-literature
Project description:With the wide use of carbapenems, carbapenem-resistant Enterobacterales have been increasingly reported worldwide. In this study, one blaOXA-181-positive Pseudocitrobacter faecalis strain was isolated from the blood culture of a patient with a bloodstream infection in China, which was its first clinical report outside Pakistan. Species identification of P. faecalis was initially performed using MALDI-TOF/MS and further confirmed by 16S rRNA gene and housekeeping gene sequencing. The antimicrobial susceptibility testing was determined through the broth microdilution method, and their clonal relationship was analyzed by pulsed-field gel electrophoresis. To study the transmission and genetic structure of the blaOXA-181 gene, a transformation test and whole-genome sequencing (WGS) were performed. The results of the antimicrobial susceptibility testing indicated this P. faecalis was resistant to carbapenems, quinolones, and commonly used β-lactam/β-lactamase inhibitor combinations. Through WGS and transformation experiments, blaOXA-181 and qnrS1 genes causing antibiotic resistance were located on a 55,148-bp length IncX3 type plasmid with a truncated ColKp3 replicon gene. As a rare species of Enterobacterales, P. faecalis was clinically reported in China for the first time, and the blaOXA-181 gene it carried was located on a globally disseminated IncX3 plasmid. The spread of such bacteria and antibiotic resistance requires more clinical attention.
| S-EPMC9220048 | biostudies-literature