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

Armalytė, Julija; Jurėnas, Dukas; Krasauskas, Renatas; Čepauskas, Albinas; Sužiedėlienė, Edita

doi:10.3389/fmicb.2018.00732

Cited by 23 publications

(15 citation statements)

References 68 publications

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“…pAB-MAL-2 detected in this study was slightly different from that in previous reports (26). The plasmid was additionally positive for a TA system showing 60% similarity to a recently described higBA2 Ab TA module on pAB120 (27). The higAB system found on the pAB-MAL-2 plasmid in our isolates was preceded by ISAba125.…”

Section: Discussioncontrasting

confidence: 93%

“…In order to better characterize the higAB system found on pAB-MAL-2, we compared it with a recently described plasmid, pAB120, having the higBA2 Ab TA module (27). Alignment of the TA components revealed 60.3% and 58.8% similarity to higB2 and higA of pAB120, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…The higBA2 gene detected in this study is a reverse TA, where the toxin gene is the first in the operon. HigB2 functions as an RNase capable of conferring maintenance of unstable plasmid in Acinetobacter, and it is neutralized with HigA2 antitoxin (27).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Whole-Genome-Sequence-Based Characterization of Extensively Drug-Resistant Acinetobacter baumannii Hospital Outbreak

Makke

Bitar

Salloum

et al. 2020

mSphere

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Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important opportunistic pathogen linked to a variety of nosocomial infections and hospital outbreaks worldwide. This study aimed at investigating and characterizing a CRAB outbreak at a large tertiary hospital in Lebanon. A total of 41 isolates were collected and analyzed using pulsed-field gel electrophoresis (PFGE). Whole-genome sequencing (WGS) was performed on all the isolates, and long-read PacBio sequencing was used to generate reference genomes. The multilocus sequence types (MLST), repertoire of resistance genes, and virulence factors were determined from the sequencing data. The plasmid content was analyzed both in silico and using the A. baumannii PCR-based replicon typing (AB-PBRT) method. Genome analysis initially revealed two clones, one carrying blaOXA-23 on Tn2006 (ST-1305, ST-195, and ST-218) and another carrying blaOXA-72 on pMAL-1 (ST-502 and ST-2059, a new ST), with the latter having two subclones, as revealed using the Bayesian transmission network. All isolates were extensively drug resistant (XDR). WGS analysis revealed the transmission pathways and demonstrated the diversity of CRAB isolates and mobile genetic elements in this health care setting. Outbreak detection using WGS and immediate implementation of infection control measures contribute to restraining the spread and decreasing mortality. IMPORTANCE Carbapenem-resistant Acinetobacter baumannii (CRAB) has been implicated in hospital outbreaks worldwide. Here, we present a whole-genome-based investigation of an extensively drug-resistant CRAB outbreak rapidly spreading and causing high incidences of mortality at numerous wards of a large tertiary hospital in Lebanon. This is the first study of its kind in the region. Two circulating clones were identified using a combination of molecular typing approaches, short- and long-read sequencing and Bayesian transmission network analysis. One clone carried blaOXA-23 on Tn2006 (ST-1305, ST-195, and ST-218), and another carried blaOXA-72 on a pMAL-1 plasmid (ST-502 and ST-2059, a new ST). A pMAL-2 plasmid was circulating between the two clones. The approaches implemented in this study and the obtained findings facilitate the tracking of outbreak scenarios in Lebanon and the region at large.

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Section: Discussioncontrasting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

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Whole-Genome-Sequence-Based Characterization of Extensively Drug-Resistant Acinetobacter baumannii Hospital Outbreak

Makke

Bitar

Salloum

et al. 2020

mSphere

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“…When we screened S. aureus genome, we observed the enriched profusion of the host inhibition of growth (HigBA) TA family, which is a sub-family of RelBE super-family [ 14 ]. The HigBA TA system has the unique genetic annotation in type II TA systems, i.e., the toxin gene is upstream of the antitoxin, which makes it different from the rest of type II TA families [ 21 , 22 ]. HigB is a ribonuclease in function followed by HigA antitoxin, and they can form a heterotetrameric complex.…”

Section: Resultsmentioning

confidence: 99%

Bioinformatics and Functional Assessment of Toxin-Antitoxin Systems in Staphylococcus aureus

Gul

Zhu

Sun

2018

Toxins

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Staphylococcus aureus is a nosocomial pathogen that can cause chronic to persistent infections. Among different mediators of pathogenesis, toxin-antitoxin (TA) systems are emerging as the most prominent. These systems are frequently studied in Escherichia coli and Mycobacterial species but rarely explored in S. aureus. In the present study, we thoroughly analyzed the S. aureus genome and screened all possible TA systems using the Rasta bacteria and toxin-antitoxin database. We further searched E. coli and Mycobacterial TA homologs and selected 67 TA loci as putative TA systems in S. aureus. The host inhibition of growth (HigBA) TA family was predominantly detected in S. aureus. In addition, we detected seven pathogenicity islands in the S. aureus genome that are enriched with virulence genes and contain 26 out of 67 TA systems. We ectopically expressed multiple TA genes in E. coli and S. aureus that exhibited bacteriostatic and bactericidal effects on cell growth. The type I Fst toxin created holes in the cell wall while the TxpA toxin reduced cell size and induced cell wall septation. Besides, we identified a new TA system whose antitoxin functions as a transcriptional autoregulator while the toxin functions as an inhibitor of autoregulation. Altogether, this study provides a plethora of new as well as previously known TA systems that will revitalize the research on S. aureus TA systems.

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“…However, unlike the Acinetobacter baumannii higBA2 operon (Armalyte et al, 2018), we found only the predicted operator regions of MtHigBA3. In the A. baumannii higBA2 operon, Armalyte et al found two distinct promoter regions located on the DNA: one for the complete TA system (higBA2) and the other for the higA2 antitoxin (Armalytė et al, 2018). The higBA3 promoter region, 230 bp of the MtHigB3 upstream DNA, includes two putative operator sites: a À35 box (DNA1) and a À10 box (DNA2).…”

Section: Analysis Of the Higba Operon Of M Tuberculosis And Identifimentioning

confidence: 99%

Induced DNA bending by unique dimerization of HigA antitoxin

Park

Kim

Pathak

et al. 2020

IUCrJ

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The bacterial toxin–antitoxin (TA) system regulates cell growth under various environmental stresses. Mycobacterium tuberculosis, the causative pathogen of tuberculosis (TB), has three HigBA type II TA systems with reverse gene organization, consisting of the toxin protein HigB and labile antitoxin protein HigA. Most type II TA modules are transcriptionally autoregulated by the antitoxin itself. In this report, we first present the crystal structure of the M. tuberculosis HigA3 antitoxin (MtHigA3) and MtHigA3 bound to its operator DNA complex. We also investigated the interaction between MtHigA3 and DNA using NMR spectroscopy. The MtHigA3 antitoxin structure is a homodimer that contains a structurally well conserved DNA-binding domain at the N-terminus and a dimerization domain at the C-terminus. Upon comparing the HigA homologue structures, a distinct difference was found in the C-terminal region that possesses the β-lid, and diverse orientations of two helix–turn–helix (HTH) motifs from HigA homologue dimers were observed. The structure of MtHigA3 bound to DNA reveals that the promoter DNA is bound to two HTH motifs of the MtHigA3 dimer presenting 46.5° bending, and the distance between the two HTH motifs of each MtHigA3 monomer was increased in MtHigA3 bound to DNA. The β-lid, which is found only in the tertiary structure of MtHigA3 among the HigA homologues, causes the formation of a tight dimerization network and leads to a unique arrangement for dimer formation that is related to the curvature of the bound DNA. This work could contribute to the understanding of the HigBA system of M. tuberculosis at the atomic level and may contribute to the development of new antibiotics for TB treatment.

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

Cited by 23 publications

References 68 publications

Whole-Genome-Sequence-Based Characterization of Extensively Drug-Resistant Acinetobacter baumannii Hospital Outbreak

Whole-Genome-Sequence-Based Characterization of Extensively Drug-Resistant Acinetobacter baumannii Hospital Outbreak

Bioinformatics and Functional Assessment of Toxin-Antitoxin Systems in Staphylococcus aureus

Induced DNA bending by unique dimerization of HigA antitoxin

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