Identification and Characterization of Type II Toxin–Antitoxin Systems in the Opportunistic Pathogen<i>Acinetobacter Baumannii</i>

Sužiedėlienė, Edita; and, Milda Jurėnaitė; Armalytė, Julija

doi:10.1002/9781119004813.ch41

Cited by 4 publications

(4 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Toxin-antitoxin modules are known plasmid stabilization factors in bacteria ( Engelberg-Kulka and Glaser, 1999 ; Hernández-Arriaga et al, 2015 ) and their presence on plasmids conferring resistance to clinically important antibiotics may contribute to the persistence and spread of antibiotic resistant strains. We have previously shown that higBA2 Ab module is widely spread among A. baumannii plasmids ( Povilonis et al, 2013 ; Sužiedėlienė et al, 2016 ), therefore we were interested whether it provides stabilization function for cognate plasmid carrying resistance genes, found in clinical A. baumannii isolates. For this purpose plasmid pAB120, which originally carries two copies of bla OXA-72 gene conferring resistance to carbapenems (meropenem and imipenem) was purified from clinical A. baumannii strain K60 and higBA2 Ab locus was deleted (Supplementary Figure S1 ).…”

Section: Resultsmentioning

confidence: 99%

“…The higBA Ab locus, with a few exceptions, is found so far on the A. baumannii plasmids, which frequently harbor antibiotic resistance genes coding for carbapenemases OXA-72, OXA-23, and OXA-58 ( Sužiedėlienė et al, 2016 ). We found that 67 out of 307 (21.8%) Acinetobacter sp.…”

Section: Discussionmentioning

confidence: 99%

“…We have recently shown that type II HigBA TA system is one of the most prevalent plasmid-borne TA systems in A. baumannii isolates of clinical origin. It is encoded by the higBA Ab operon, where higB Ab toxin gene (357 bp) precedes higA Ab antitoxin (303 bp) ( Jurenaite et al, 2013 ; Sužiedėlienė et al, 2016 ). higBA Ab locus was also found to be encoded by the newly observed ubiquitous A. baumannii 11 kb plasmid pAB120.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The higBA Toxin-Antitoxin Module From the Opportunistic Pathogen Acinetobacter baumannii – Regulation, Activity, and Evolution

et al. 2018

Self Cite

View full text Add to dashboard Cite

Acinetobacter baumannii is one of the major causes of hard to treat multidrug-resistant hospital infections. A. baumannii features contributing to its spread and persistence in clinical environment are only beginning to be explored. Bacterial toxin-antitoxin (TA) systems are genetic loci shown to be involved in plasmid maintenance and proposed to function as components of stress response networks. Here we present a thorough characterization of type II system of A. baumannii, which is the most ubiquitous TA module present in A. baumannii plasmids. higBA of A. baumannii is a reverse TA (the toxin gene is the first in the operon) and shows little homology to other TA systems of RelE superfamily. It is represented by two variants, which both are functional albeit exhibit strong difference in sequence conservation. The higBA2 operon is found on ubiquitous 11 Kb pAB120 plasmid, conferring carbapenem resistance to clinical A. baumannii isolates and represents a higBA variant that can be found with multiple sequence variations. We show here that higBA2 is capable to confer maintenance of unstable plasmid in Acinetobacter species. HigB2 toxin functions as a ribonuclease and its activity is neutralized by HigA2 antitoxin through formation of an unusually large heterooligomeric complex. Based on the in vivo expression analysis of gfp reporter gene we propose that HigA2 antitoxin and HigBA2 protein complex bind the higBA2 promoter region to downregulate its transcription. We also demonstrate that higBA2 is a stress responsive locus, whose transcription changes in conditions encountered by A. baumannii in clinical environment and within the host. We show elevated expression of higBA2 during stationary phase, under iron deficiency and downregulated expression after antibiotic (rifampicin) treatment.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The higBA Toxin-Antitoxin Module From the Opportunistic Pathogen Acinetobacter baumannii – Regulation, Activity, and Evolution

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…The presence of these modules on plasmids not only ensures the persistence of the plasmids within a cell line but may also play a role in bacterial virulence (Lobato-Márquez et al, 2016). TA modules been previously described in A. baumannii plasmids; therefore, we searched for the presence of these modules in our 173 plasmids (Jurenaite et al, 2013;Sužiedėlienė et al, 2016;Armalytė et al, 2018). We determined that 108 of them have TA modules belonging to nine different classes.…”

Section: Toxin-antitoxin Modulesmentioning

confidence: 99%

Structure and Evolution of Acinetobacter baumannii Plasmids

et al. 2020

View full text Add to dashboard Cite

Acinetobacter baumannii is an emergent bacterial pathogen that provokes many types of infections in hospitals around the world. The genome of this organism consists of a chromosome and plasmids. These plasmids vary over a wide size range and many of them have been linked to the acquisition of antibiotic-resistance genes. Our bioinformatic analyses indicate that A. baumannii plasmids belong to a small number of plasmid lineages. The general structure of these lineages seems to be very stable and consists not only of genes involved in plasmid maintenance functions but of gene sets encoding poorly characterized proteins, not obviously linked to survival in the hospital setting, and opening the possibility that they improve the parasitic properties of plasmids. An analysis of genes involved in replication, suggests that members of the same plasmid lineage are part of the same plasmid incompatibility group. The same analysis showed the necessity of classifying the Rep proteins in ten new groups, under the scheme proposed by Bertini et al. (2010). Also, we show that some plasmid lineages have the potential capacity to replicate in many bacterial genera including those embracing human pathogen species, while others seem to replicate only within the limits of the Acinetobacter genus. Moreover, some plasmid lineages are widely distributed along the A. baumannii phylogenetic tree. Despite this, a number of them lack genes involved in conjugation or mobilization functions. Interestingly, only 34.6% of the plasmids analyzed here possess antibiotic resistance genes and most of them belong to fourteen plasmid lineages of the twenty one described here. Gene flux between plasmid lineages appears primarily limited to transposable elements, which sometimes carry antibiotic resistance genes. In most plasmid lineages transposable elements and antibiotic resistance genes are secondary acquisitions. Finally, broad host-range plasmids appear to have played a crucial role.

show abstract