Promoters of Colistin Resistance in <i>Acinetobacter baumannii</i> Infections

Nurtop, Elif; Bilman, Fulya Bayındır; Menekşe, Şirin; Azap, Özlem Kurt; Gönen, Mehmet; Ergönül, Önder; Can, Füsun

doi:10.1089/mdr.2018.0396

Cited by 29 publications

(49 citation statements)

References 25 publications

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“…A point mutation (K117P) in the lpxD gene matched with mutations detected previously by Nurtop et al [41], who showed a synergistic interaction between an IpxD mutation and mutations in pmrCAB, also proved in our clinical colistin-resistant MS34Col-R strain, although this IpxD mutation in the induced colistin-resistant A. baumannii strain MS64Col-R was the only mutation identified, nevertheless strongly associated with colistin resistance. This point mutation leads to a disruption of polymerization that affects the resulting enzyme binding affinity and consequently causes a modification in LPS [10,42].…”

Section: Discussionsupporting

confidence: 87%

Acquisition of Colistin Resistance Links Cell Membrane Thickness Alteration with a Point Mutation in the lpxD Gene in Acinetobacter baumannii

et al. 2020

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Acinetobacter baumannii is one of the most common causes of nosocomial infections in intensive care units. Its ability to acquire diverse mechanisms of resistance limits the therapeutic choices for its treatment. This especially concerns colistin, which has been reused recently as a last-resort drug against A. baumannii. Here, we explored the impact of gaining colistin resistance on the susceptibility of A. baumannii to other antibiotics and linked colistin resistance acquisition to a gene mutation in A. baumannii. The susceptibility of 95 A. baumannii isolates revealed that 89 isolates were multi-drug resistance (MDR), and nine isolates were resistant to colistin. Subsequently, three isolates, i.e., MS48, MS50, and MS64, exhibited different resistance patterns when colistin resistance was induced and gained resistance to almost all tested antibiotics. Upon TEM examination, morphological alterations were reported for all induced isolates and a colistin-resistant clinical isolate (MS34Col-R) compared to the parental sensitive strains. Finally, genetic alterations in PmrB and LpxACD were assessed, and a point mutation in LpxD was identified in the MS64Col-R and MS34Col-R mutants, corresponding to Lys117Glu substitution in the lipid-binding domain. Our findings shed light on the implications of using colistin in the treatment of A. baumannii, especially at sub-minimum inhibitory concentrations concentrations, since cross-resistance to other classes of antibiotics may emerge, beside the rapid acquisition of resistance against colistin itself due to distinct genetic events.

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Section: Discussionsupporting

confidence: 87%

Acquisition of Colistin Resistance Links Cell Membrane Thickness Alteration with a Point Mutation in the lpxD Gene in Acinetobacter baumannii

et al. 2020

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“…In this study, clinical isolates of CR-ColRAB and CR-ColSAB were characterized for multiple colistin resistance mechanisms. Mutation analysis in lpxACD identified three nonsynonymous mutations; Q4K, V63I and E117K within lpxD in both CR-ColRAB and CR-ColSAB which concurs with previous studies [26,27]. Recent studies report that mutations in pmrB as the major contributor for colistin resistance in A. baumannii [24,26,28,29].The current study identified a non-synonymous mutation, A138T in pmrB while previous studies report other amino-acid substitutions together with A138T which is contrary to the current study [24,26,29].…”

Section: Discussionsupporting

confidence: 89%

“…It is not subject to copyright under 17 USC The copyright holder for this preprint this version posted January 7, 2021. ; https://doi.org/10.1101/2021.01.07.425695 doi: bioRxiv preprint study, both CR-ColRAB and CR-ColSAB has lpxD mutation, E117K in combination with A138T-A444V mutation in pmrB. This observation indicates that mutations in lpxD alone and pmrB alone may not be sufficient to induce colistin resistance and support the presence of synergistic activity of mutations within these genes in promoting colistin resistance [26].…”

Section: Discussionmentioning

confidence: 94%

Colistin resistance inAcinetobacter baumanniiis driven by multiple genomic traits: Evaluating the role of ISAba1-driveneptAoverexpression among Indian isolates

Vijayakumar

Jacob

Vasudevan

et al. 2021

Preprint

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Colistin resistance in Acinetobacter baumannii is mediated by multiple mechanisms. Recently, mutations within pmrAB two component system and overexpression of eptA due to upstream insertion of ISAba1 play a major role.To characterize colistin resistance mechanisms among the clinical isolates of A. baumannii in India. A total of 224 clinical isolates of A. baumannii collected from 2016 to 2019 were included in this study. Mutations within lipid A biosynthesis and pmrAB genes were characterized by Whole Genome Shotgun sequencing. Twenty eight complete genomes were further characterized for insertional inactivation of lpx genes and the association of ISAba1-eptA using hybrid assembly approach. Non-sysnonymous mutations like M12I in pmrA, A138T and A444V in pmrB and E117K in lpxD were identified. Four of the five colistin resistant A.baumannii isolates had insertion of ISAba1 upstream eptA. No mcr genes were identified.Overall, the present study highlights the diversity of colistin resistance mechanisms in A. baumannii. ISAba1-driven eptA overexpression could be responsible for colistin resistance among Indian isolates of colistin resistant A. baumannii.

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“…According to our data, things are getting worse in Guangzhou, more than 80% of A. baumannii isolates showed resistance to imipenem and meropenem, and only tigecycline and polymyxin remained effective. However, tigecycline and polymyxin resistance A. baumannii has been reported and the resistance rate kept rising [24][25][26][27]. Therefore, monitoring and controlling the spread of A. baumannii is urgent.…”

Section: Discussionmentioning

confidence: 99%

A New OXA-66-harboring Acinetobacter Baumannii Sub-Clonal Complex 195 is Spreading Widely in Guangzhou, China, A Multicenter Study

Yu-jun

Huang

Wang

et al. 2020

Preprint

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Objectives The clonal spread of Acinetobacter baumannii (A. baumannii) is an emerging problem. We analyzed the molecular epidemiology of A. baumannii isolated from 5 teaching hospitals in Guangzhou, China. Methods 138 A. baumannii isolates were collected. Multilocus sequence typing (MLST) was used to assess the genetic relationships among the isolates. The blaOXA-51-like gene was amplified and then sequenced. Results Most of the isolates (55.8%, 77/138) were obtained from intensive care units (ICUs). The respiratory system was the most common site where A. baumannii was found (72.5%, 100/138). A. baumannii remained susceptible to polymyxin and tigecycline, but the susceptibility to other antimicrobial agents was below 30%. We used MLST to group the A. baumannii isolates into 8 existing sequence types (STs) and 17 new STs. With the predicted founder ST195 (accounted for 35.5% of all isolates, 49/138), Clonal complex (CC) 195 was the most prevalent and widely spread STs in the hospital environment. All ST195 isolates harbored OXA-66 according to the blaOXA-51-like gene sequencing. But each hospital had its unique epidemiological feature. Conclusions OXA-66 gene harboring CC195 was the most epidemic STs in Guangzhou, China. Health care facilities should develop their own management strategy.

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Promoters of Colistin Resistance in Acinetobacter baumannii Infections

Cited by 29 publications

References 25 publications

Acquisition of Colistin Resistance Links Cell Membrane Thickness Alteration with a Point Mutation in the lpxD Gene in Acinetobacter baumannii

Acquisition of Colistin Resistance Links Cell Membrane Thickness Alteration with a Point Mutation in the lpxD Gene in Acinetobacter baumannii

Colistin resistance inAcinetobacter baumanniiis driven by multiple genomic traits: Evaluating the role of ISAba1-driveneptAoverexpression among Indian isolates

A New OXA-66-harboring Acinetobacter Baumannii Sub-Clonal Complex 195 is Spreading Widely in Guangzhou, China, A Multicenter Study

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