Dataset Information

Origin of OXA-23 Variant OXA-239 from a Recently Emerged Lineage of Acinetobacter baumannii International Clone V.

ABSTRACT: Over the last few decades, carbapenemase-producing Acinetobacter baumannii has become a major cause of nosocomial infections all over the world. However, the genome identity of lineages of this species in Latin America has not been studied as much as in developed countries. Here, through a population genomics approach considering the whole genomes of 148 isolates (almost 40 from Mexico and Honduras), we describe the recent emergence of the lineage sequence type 758 (ST758), which belongs to the international clone V and has spread out to Canada, Mexico, Honduras, and Colombia. Notably, this lineage was found to coexist with other A. baumannii lineages in hospitals in Mexico and Honduras. Isolates from this lineage show considerable variation in antibiotic resistance profiles, but most of them are resistant to carbapenems. Moreover, we found a variety of acquired oxacillinase (OXA) families within this lineage and tracked the very recent inception, and subsequent horizontal transmission, of the OXA-239 carbapenemase. This work highlights the urgent need to investigate recently emerged lineages of this species in Latin America and elsewhere, as these might harbor novel antibiotic resistance genes.IMPORTANCE A. baumannii is a major cause of nosocomial infections all over the world. Although many isolates from developed countries have been studied in terms of their genome sequence, isolates from Latin America have been much less studied. In this study, using a population genomics approach considering the whole genomes of 148 isolates, we describe the recent emergence of the lineage ST758 endemic to Latin America and the inception of the OXA-239 carbapenemase. Our study highlights the urgent need to investigate recently emerged lineages of this species in Latin America and elsewhere, as these might harbor novel antibiotic resistance genes.

SUBMITTER: Grana-Miraglia L

PROVIDER: S-EPMC6952199 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Origin of OXA-23 Variant OXA-239 from a Recently Emerged Lineage of Acinetobacter baumannii International Clone V.

Graña-Miraglia Lucia L Evans Benjamin A BA López-Jácome Luis E LE Hernández-Durán Melissa M Colín-Castro Claudia Adriana CA Volkow-Fernández Patricia P Cevallos Miguel A MA Franco-Cendejas Rafael R Castillo-Ramírez Santiago S

mSphere 20200108 1

Over the last few decades, carbapenemase-producing <i>Acinetobacter baumannii</i> has become a major cause of nosocomial infections all over the world. However, the genome identity of lineages of this species in Latin America has not been studied as much as in developed countries. Here, through a population genomics approach considering the whole genomes of 148 isolates (almost 40 from Mexico and Honduras), we describe the recent emergence of the lineage sequence type 758 (ST758), which belongs ...[more]

PMID: 31915222

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Project description:Carbapenem resistant Acinetobacter baumannii (CRAB) represents one of the most challenging pathogens in clinical settings. Colistin is routinely used for treatment of infections by this pathogen, but increasing colistin resistance has been reported. We obtained 122 CRAB isolates from nine Greek hospitals between 2015 and 2017, and those colistin resistant (ColR; N = 40, 32.8%) were whole genome sequenced, also by including two colistin susceptible (ColS) isolates for comparison. All ColR isolates were characterized by a previously described mutation, PmrBA226V, which was associated with low-level colistin resistance. Some isolates were characterized by additional mutations in PmrB (E140V or L178F) or PmrA (K172I or D10N), first described here, and higher colistin minimum inhibitory concentrations (MICs), up to 64 mg/L. Mass spectrometry analysis of lipid A showed the presence of a phosphoethanolamine (pEtN) moiety on lipid A, likely resulting from the PmrA/B-induced pmrC overexpression. Interestingly, also the two ColS isolates had the same lipid A modification, suggesting that not all lipid A modifications lead to colistin resistance or that other factors could contribute to the resistance phenotype. Most of the isolates (N = 37, 92.5%) belonged to the globally distributed international clone (IC) 2 and comprised four different sequence types (STs) as defined by using the Oxford scheme (ST 425, 208, 451, and 436). Three isolates belonged to IC1 and ST1567. All the genomes harbored an intrinsic bla OXA-51 group carbapenemase gene, where bla OXA-66 and bla OXA-69 were associated with IC2 and IC1, respectively. Carbapenem resistance was due to the most commonly reported acquired carbapenemase gene bla OXA-23, with ISAba1 located upstream of the gene and likely increasing its expression. The armA gene, associated with high-level resistance to aminoglycosides, was detected in 87.5% of isolates. Collectively, these results revealed a convergent evolution of different clonal lineages toward the same colistin resistance mechanism, thus limiting the effective therapeutic options for the treatment of CRAB infections.

Project description:Purpose:A novel variant of OXA-23, named OXA-423, was identified in an Acinetobacter baumannii clinical isolate. The aim of this study was to analyse the resistance phenotype of OXA-423. Methods:The A. baumannii strain WY-0713 was isolated from an intensive care unit patient. PCR was used to detect the bla OXA-23-like genes. Amplifying, cloning and sequencing were performed for the complete bla OXA-23-like. The novel bla OXA-423 and its ancestor bla OXA-23 were cloned into the expression vector pET-28b(+), and transformed into E. coli Rosetta (DE3) for antibiotic susceptibility testing. SDS-PAGE, modified Hodge test and CarbaNP test were used for detecting the expression of OXA-423 and OXA-23. Results:PCR screening of A. baumannii WY-0713 was positive for bla OXA-23-like genes. Sequencing of the PCR product identi?ed a novel bla OXA-23-like, named bla OXA-423 which encoding OXA-423. OXA-423 differed from OXA-23 by a crucial amino acid substitution (Val128Ala). The V128A substitution was located at the conserved active-site motifs SAV of OXA-23. Antibiotic susceptibility testing performed using isogenic E. coli showed that the MICs of E. coli Rosetta (pET-OXA-423) for penicillins and carbapenems were lower (reduced MICs 4-fold to 16-fold) than that of E. coli Rosetta (pET-OXA-23). The MICs of cefotaxime, ceftazidime and aztreonam for both transformants remained the same as the acceptor strain. Moreover, OXA-423 was slightly inhibited by sulbactam, clavulanic acid and tazobactam. SDS-PAGE analysis showed that OXA-423 and OXA-23 were conspicuously expressed. Modified Hodge test and CarbaNP test were positive demonstrated both of them were functional. Conclusion:OXA-423, the first report of an amino acid substitution located at conserved active-site motifs of OXA-23, conferred lower MIC values of penicillins and carbapenems as compared with OXA-23, while without affecting the resistance pro?les of expanded-spectrum cephalosporins and aztreonam.

Dataset Information

Origin of OXA-23 Variant OXA-239 from a Recently Emerged Lineage of Acinetobacter baumannii International Clone V.

Publications

Origin of OXA-23 Variant OXA-239 from a Recently Emerged Lineage of Acinetobacter baumannii International Clone V.

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