Dataset Information

"Roar" of blaNDM-1 and "silence" of blaOXA-58 co-exist in Acinetobacter pittii.

ABSTRACT: Acinetobacter pittii 44551 was recovered from a patient with gout combined with tuberculosis and was found to harbor the carbapenemase genes blaNDM-1 and blaOXA-58 on two different plasmids pNDM-44551 and pOXA58-44551, respectively. pNDM-44551 displayed high self-transferability across multiple bacterial species, while pOXA58-44551 was likely co-transferable with pNDM-44551 into A. baumannii receipts. pNDM-44551 was a close variant of the previously characterized pNDM-BJ01, and the blaNDM-1 gene cluster was arranged sequentially as orfA, ISAba14, aphA6, ISAba125, blaNDM-1, bleMBL, ΔtrpF, dsbC, tnpR, and zeta. pOXA58-44551 was a repAci9-containing plasmid, and blaOXA-58 was embedded in a 372F-ISAba3-like-blaOXA-58-ISAba3 structure. The mobile genetic platforms of blaNDM-1 and blaOXA-58 herein showed some differences from their previously characterized variants. The production of NDM-1 in strain 44551 contributed the majority to its high resistance to carbapenems, while the blaOXA-58 stayed silent most likely due to the lack of an upstream promoter to drive its transcription. Increased surveillance of Acinetobacter co-harboring blaNDM-1 (active) and blaOXA-58 (either active or silent) is urgently needed.

SUBMITTER: Zhou S

PROVIDER: S-EPMC5155454 | biostudies-other | 2015 Mar

REPOSITORIES: biostudies-other

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"Roar" of blaNDM-1 and "silence" of blaOXA-58 co-exist in Acinetobacter pittii.

Zhou Shuru S Chen Xin X Meng Xiaobin X Zhang Guoxiong G Wang Jie J Zhou Dongsheng D Guo Xuemin X

Scientific reports 20150310

Acinetobacter pittii 44551 was recovered from a patient with gout combined with tuberculosis and was found to harbor the carbapenemase genes blaNDM-1 and blaOXA-58 on two different plasmids pNDM-44551 and pOXA58-44551, respectively. pNDM-44551 displayed high self-transferability across multiple bacterial species, while pOXA58-44551 was likely co-transferable with pNDM-44551 into A. baumannii receipts. pNDM-44551 was a close variant of the previously characterized pNDM-BJ01, and the blaNDM-1 gene ...[more]

PMID: 25755005

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Project description:We characterize by whole-plasmid-sequence (WPS) two-plasmid-borne bla OXA-58 obtained from Acinetobacter seifertii (Asp-1069) and A. baumannii (Acb-45063) clinical strains recovered 17?years apart from distinct Brazilian regions. Multilocus sequence type (MLST) analysis showed that the Asp-1069 and Acb-45063 strains belong to ST551 and ST15/CC15, respectively. WPS analysis demonstrated that bla OXA-58 was located in two distinct plasmids named pAs1069_a (24,672?bp/44 open reading frames [ORFs]) and pAb45063_b (19,808?bp/24 ORFs), which belong to the GR8/GR23 (repAci23) and GR4 (repAci4) incompatibility groups, respectively. The genetic environments surrounding bla OXA-58 revealed that it was flanked by two intact ISAba3 copies on pAb45063_b, which differed from pAs1069_a. In the latter, the upstream ISAba3 copy was truncated by insertion of ISAba825 element. Although Re27-specific recombination sites were found adjacent to ISAba3-bla OXA-58-ISAba3 arrangement on pAb45063_b, such structures were absent on pAs1069_a. The conserved ISAba125-araC1-lysE arrangement was disrupted by TnaphA6 harboring the aminoglycosides resistance gene aphA6 on pAs1069_a, while an IS26-bla TEM-1-aac(3)-IIa-IS26 genetic structure was found upstream from ISAba3-bla OXA-58-ISAba3 on pAb45063_b. Other two plasmids, pAb45063_a (183,767?bp/209 ORFs) and pAs1069_b (13,129?bp/14 ORFs), were also found in the OXA-58-producing Acinetobacter species strains, harboring the strA and strB genes and the sul2 gene, which confer resistance to streptomycin and sulfonamides, respectively. The plasmid-mediated virulence factors corresponding to genes tonB, spl, glmM, ppa, sulP, and map were found in both strains, as well distinct toxin-antitoxin system-encoding genes stbD and relE (pAs1069_a), brnT and brnA (pAb45063_b), and xreE (pAb45063_a). Although infrequently reported in Brazil, plasmid-borne bla OXA-58 showed a complex and diverse genetic backbone that confers stability in different Acinetobacter species that have been isolated from nosocomial settings over time.IMPORTANCE Although the bla OXA-58 gene has been infrequently described in Brazil, contrasting with other bordering South American countries, we verified the maintenance of this resistance determinant over time among carbapenem-resistant Acinetobacter species isolates, not only in nosocomial settings but also in the environment. In addition, to the best of our knowledge, this is the first study to have used WPS analysis to evaluate the genetic surroundings of bla OXA-58 in Brazil. Moreover, the A. seifertii and A. baumannii clinical strains evaluated in this study were recovered 17?years apart in hospitals located in distinct Brazilian geographic regions.

Project description:Members of the genus Acinetobacter possess distinct plasmid types which provide effective platforms for the acquisition, evolution, and dissemination of antimicrobial resistance structures. Many plasmid-borne resistance structures are bordered by short DNA sequences providing potential recognition sites for the host XerC and XerD site-specific tyrosine recombinases (XerC/D-like sites). However, whether these sites are active in recombination and how they assist the mobilization of associated resistance structures is still poorly understood. Here we characterized the plasmids carried by Acinetobacter baumannii Ab242, a multidrug-resistant clinical strain belonging to the ST104 (Oxford scheme) which produces an OXA-58 carbapenem-hydrolyzing class-D ?-lactamase (CHDL). Plasmid sequencing and characterization of replication, stability, and adaptive modules revealed the presence in Ab242 of three novel plasmids lacking self-transferability functions which were designated pAb242_9, pAb242_12, and pAb242_25, respectively. Among them, only pAb242_25 was found to carry an adaptive module encompassing an ISAba825-blaOXA-58 arrangement accompanied by a TnaphA6 transposon, the whole structure conferring simultaneous resistance to carbapenems and aminoglycosides. Ab242 plasmids harbor several XerC/D-like sites, with most sites found in pAb242_25 located in the vicinity or within the adaptive module described above. Electrotransformation of susceptible A. nosocomialis cells with Ab242 plasmids followed by imipenem selection indicated that the transforming plasmid form was a co-integrate resulting from the fusion of pAb242_25 and pAb242_12. Further characterization by cloning and sequencing studies indicated that a XerC/D site in pAb242_25 and another in pAb242_12 provided the active sister pair for the inter-molecular site-specific recombination reaction mediating the fusion of these two plasmids. Moreover, the resulting co-integrate was found also to undergo intra-molecular resolution at the new pair of XerC/D sites generated during fusion thus regenerating the original pAb242_25 and pAb242_12 plasmids. These observations provide the first evidence indicating that XerC/D-like sites in A. baumannii plasmids can provide active pairs for site-specific recombination mediating inter-molecular fusions and intra-molecular resolutions. The overall results shed light on the evolutionary dynamics of A. baumannii plasmids and the underlying mechanisms of dissemination of genetic structures responsible for carbapenem and other antibiotics resistance among the Acinetobacter clinical population.

Dataset Information

"Roar" of blaNDM-1 and "silence" of blaOXA-58 co-exist in Acinetobacter pittii.

Publications

"Roar" of blaNDM-1 and "silence" of blaOXA-58 co-exist in Acinetobacter pittii.

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