Old drug, new findings: colistin resistance and dependence of Acinetobacter baumannii

Ko, Kwan Soo; Choi, Younghoon; Lee, Ji-Young

doi:10.23838/pfm.2017.00184

Cited by 22 publications

(18 citation statements)

References 77 publications

(92 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The colonies that survived in colistin-containing media showed different amino acid substitutions, even from the same isolate. Only two amino acid alterations (P170L and S17R in PmrB) have been reported in previous studies [25], but others including mutations in LpxACD were newly identified in this study. Although it is required to investigate if the mutations would be associated with colistin resistance, diverse colistin-resistant subpopulations of the original isolates may have been present prior to the start of experiments.…”

Section: Discussionmentioning

confidence: 47%

“…Acinetobacter baumannii is a catalase-positive, gram-negative, and opportunistic pathogen responsible for life-threatening infectious disease conditions including pneumonia, sepsis, and meningitis [ 1 ]. Treating A. baumannii infections is challenging due to the remarkable ability of this pathogen to acquire antibiotic resistance [ 2 ]. A. baumannii has also been listed among Priority 1 pathogens for which new antibiotics are urgently needed by World Health Organization (WHO) in 2017 [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Two types of colistin heteroresistance in Acinetobacter baumannii isolates

Hong

Kim

2020

Emerging Microbes & Infections

Self Cite

View full text Add to dashboard Cite

In this study, we investigated the colistin heteroresistance patterns in Acinetobacter baumannii isolates. To identify colistin heteroresistance, population analysis profiling was performed for six in vitro colistin-susceptible A. baumannii isolates. Survival rates with and without prior exposure to colistin (at concentrations between 0 and 32 mg/L) were measured in media with and without colistin. Amino acid substitutions were also detected in colonies that survived in media with 4 mg/L colistin without further antibiotic treatment in six A. baumannii isolates. A stability test was also performed to investigate whether colistin resistance is maintained without antibiotic treatment. Although only three isolates showed typical colistin heteroresistance pattern, colistin-resistant populations were identified even without prior exposure to colistin in all A. baumannii isolates. Nearly all colonies of typical colistin-heteroresistant isolates (Type I heteroresistance) that survived after exposure to high colistin concentrations were found to be colistinresistant, whereas no resistant colonies were identified in the other isolates (Type II heteroresistance). Stability tests showed that most of the surviving populations in media with 4 mg/L colistin without further antibiotic exposure failed to preserve resistance to colistin. Colistin-resistant populations also showed either no change in amino acid sequences, or diverse amino acid substitutions. We identified two types of colistin heteroresistance in A. baumannii isolates. Because Type I colistin-heteroresistant A. baumannii isolates could not be eradicated in vitro by high concentrations of colistin, differentiating two colistin heteroresistance types would be important for the treatment of A. baumannii infections using colistin.

show abstract

Section: Discussionmentioning

confidence: 47%

Section: Introductionmentioning

confidence: 99%

Two types of colistin heteroresistance in Acinetobacter baumannii isolates

Hong

Kim

2020

Emerging Microbes & Infections

Self Cite

View full text Add to dashboard Cite

show abstract

“…The main mechanism of colistin resistance in A. baumannii is the modification of lipopolysaccharide (LPS) by mutations in PmrA/PmrB two-component system (Ko et al 2017). These mutations cause upregulation of the pmr-CAB operon, which results in the synthesis and addition of positively charged phosphoethanolamine to the LPS.…”

Section: Discussionmentioning

confidence: 99%

Colistin heteroresistance in carbapenem-resistant Acinetobacter baumannii clinical isolates from a Thai university hospital

Thet

Lunha

Srisrattakarn

et al. 2020

World J Microbiol Biotechnol

View full text Add to dashboard Cite

Colistin is the last resort for the treatment of infections with carbapenem-resistant (CR) Gram-negative bacteria particularly Acinetobacter baumannii (CRAB). Currently, both colistin-resistant and-heteroresistant A. baumannii isolates have been reported globally. We therefore investigated the colistin heteroresistance rate in 75 non-duplicate colistin-susceptible CRAB clinical isolates from a Thai university collected in 2016. Minimum inhibitory concentrations (MICs) of colistin for all isolates were determined by broth microdilution method and carbapenemase genes were detected by PCR methods. All isolates were genotyped by ERIC-PCR method and screened for colistin heteroresistance by modified population analysis profile (PAP) method. The colistin MIC range for the 75 isolates was 0.5-2 µg/mL, with MIC 50 and MIC 90 of 1 and 2 µg/mL, respectively. Thirty-three isolates (44%) were considered colistin-heteroresistant with subpopulations growing at 3-8 μg/mL of colistin. After three daily passages of the subpopulations on antibiotic-free medium, their colistin MICs ranged from 4 to > 32 µg/mL, with MIC 50 and MIC 90 of 32 and > 32 µg/mL, respectively. Eight different ERIC-PCR profiles were obtained among the 33 isolates and all carried bla OXA-23-like. The high rate of colistin heteroresistance in the CRAB isolates highlights the possibility of treatment failure of CRAB infections by colistin due to the selection of colistin-resistant subpopulations.

show abstract

“…Colistin-susceptible A. baumannii strains may develop dependence after exposure to colistin in vitro [ 12 , 13 , 14 ]. Colistin dependence is not rare, as many as 32.9% of colistin-susceptible isolates were able to do so [ 14 ], most of them were otherwise multidrug-resistant and able to cause infection in mice [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Colistin Dependence in Extensively Drug-Resistant Acinetobacter baumannii Strain Is Associated with ISAjo2 and ISAba13 Insertions and Multiple Cellular Responses

Chamoun

Welander

Martis

et al. 2021

IJMS

View full text Add to dashboard Cite

The nosocomial opportunistic Gram-negative bacterial pathogen Acinetobacter baumannii is resistant to multiple antimicrobial agents and an emerging global health problem. The polymyxin antibiotic colistin, targeting the negatively charged lipid A component of the lipopolysaccharide on the bacterial cell surface, is often considered as the last-resort treatment, but resistance to colistin is unfortunately increasing worldwide. Notably, colistin-susceptible A. baumannii can also develop a colistin dependence after exposure to this drug in vitro. Colistin dependence might represent a stepping stone to resistance also in vivo. However, the mechanisms are far from clear. To address this issue, we combined proteogenomics, high-resolution microscopy, and lipid profiling to characterize and compare A. baumannii colistin-susceptible clinical isolate (Ab-S) of to its colistin-dependent subpopulation (Ab-D) obtained after subsequent passages in moderate colistin concentrations. Incidentally, in the colistin-dependent subpopulation the lpxA gene was disrupted by insertion of ISAjo2, the lipid A biosynthesis terminated, and Ab-D cells displayed a lipooligosaccharide (LOS)-deficient phenotype. Moreover, both mlaD and pldA genes were perturbed by insertions of ISAjo2 and ISAba13, and LOS-deficient bacteria displayed a capsule with decreased thickness as well as other surface imperfections. The major changes in relative protein abundance levels were detected in type 6 secretion system (T6SS) components, the resistance-nodulation-division (RND)-type efflux pumps, and in proteins involved in maintenance of outer membrane asymmetry. These findings suggest that colistin dependence in A. baumannii involves an ensemble of mechanisms seen in resistance development and accompanied by complex cellular events related to insertional sequences (ISs)-triggered LOS-deficiency. To our knowledge, this is the first study demonstrating the involvement of ISAjo2 and ISAba13 IS elements in the modulation of the lipid A biosynthesis and associated development of dependence on colistin.

show abstract

Old drug, new findings: colistin resistance and dependence of Acinetobacter baumannii

Cited by 22 publications

References 77 publications

Two types of colistin heteroresistance in Acinetobacter baumannii isolates

Two types of colistin heteroresistance in Acinetobacter baumannii isolates

Colistin heteroresistance in carbapenem-resistant Acinetobacter baumannii clinical isolates from a Thai university hospital

Colistin Dependence in Extensively Drug-Resistant Acinetobacter baumannii Strain Is Associated with ISAjo2 and ISAba13 Insertions and Multiple Cellular Responses

Contact Info

Product

Resources

About