Distribution of carbapenem resistant Acinetobacter baumannii with blaADC-30 and induction of ADC-30 in response to beta-lactam antibiotics

Ingti, Birson; Upadhyay, S.K.; Hazarika, Monalisha; Khyriem, Annie Bakorlin; Paul, Deepjyoti; Bhattacharya, Prithwis; Joshi, S. R.; Bora, Debajyoti; Dhar, Debadatta; Bhattacharjee, Amitabha

doi:10.1016/j.resmic.2020.01.002

Cited by 20 publications

(20 citation statements)

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“…E. coli exhibits resistance to variable antibiotics, mainly extended-spectrum β-lactams (ESBLs) and carbapenem. ESBLs producers are isolates that are resistant to penicillins and cephalosporins [7]. They were observed either as variants of TEM and SHV or the CTX-M enzyme.…”

Section: Introductionmentioning

confidence: 99%

Genetic characterization of extended-spectrum β-Lactamase- and carbapenemase-producing Escherichia coli isolated from Egyptian hospitals and environments

et al. 2021

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Over the past decades, Escherichia coli (E. coli) have acquired extensive resistance to antibiotics; especially β- lactams. This study aimed to investigate the frequency of Extended-spectrum β-lactamase (ESBL) and carbapenemase producers among E. coli isolates and their correlation with serotypes, phylogenetic background, and pathogenicity associated islands. A total of 105 E. coli strains were isolated and subjected to antimicrobial susceptibility testing against β-lactam antibiotics. All isolates showed a high resistance profile. Resistant isolates were tested for ESBL and carbapenemase production. Fifty-three and 18 isolates were positive for ESBL and carbapenemase producers, respectively. ESBL and carbapenemase genes were detected by PCR. TEM gene was the most prevalent gene among all isolates followed by SHV and CTX-M15. In carbapenemase-producers, OXA-48 and IMP were the predominant genes. Enteropathogenic E. coli (EPEC) and Enterohemorrhagic E. coli (EHEC) were the major producers of ESBL and carbapenemase, respectively as indicated by serodiagnosis. They were further assessed for the presence of pathogenicity islands (PAIs) and phylogenetic background. The most predominant DEC PAI and ExPEC PAI were HPI and IICFT073. Most clinically ESBL-producers were group D and B2 while environmentally ones were group B1 and A. On contrary, clinically carbapenemase-producers belonged to group C and D. In conclusion, our study confirms the importance of phylogenetic group D, B2, and C origin for antibiotic resistance in E. coli. Ultimately, our findings support the fact that environmental isolates contribute to the local spread of E. coli pathogenicity in Egypt and these isolates maybe serve as reservoirs for transmission of resistance.

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Section: Introductionmentioning

confidence: 99%

Genetic characterization of extended-spectrum β-Lactamase- and carbapenemase-producing Escherichia coli isolated from Egyptian hospitals and environments

et al. 2021

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“…Several ADC variants have been described, many of which exhibit extended spectrum antibiotic resistance [48,49]. For example, ADC-30 provides resistance not only to cephalosporins, but also to carbapenems and sulbactam [50,51]. Finally, phosphoproteomic analysis revealed that dephosphorylation of ADC may lead to imipenem resistance in clinical isolates [52].…”

Section: Class Cmentioning

confidence: 99%

Acinetobacter baumannii Antibiotic Resistance Mechanisms

et al. 2021

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Acinetobacter baumannii is a Gram-negative ESKAPE microorganism that poses a threat to public health by causing severe and invasive (mostly nosocomial) infections linked with high mortality rates. During the last years, this pathogen displayed multidrug resistance (MDR), mainly due to extensive antibiotic abuse and poor stewardship. MDR isolates are associated with medical history of long hospitalization stays, presence of catheters, and mechanical ventilation, while immunocompromised and severely ill hosts predispose to invasive infections. Next-generation sequencing techniques have revolutionized diagnosis of severe A. baumannii infections, contributing to timely diagnosis and personalized therapeutic regimens according to the identification of the respective resistance genes. The aim of this review is to describe in detail all current knowledge on the genetic background of A. baumannii resistance mechanisms in humans as regards beta-lactams (penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors), aminoglycosides, tetracyclines, fluoroquinolones, macrolides, lincosamides, streptogramin antibiotics, polymyxins, and others (amphenicols, oxazolidinones, rifamycins, fosfomycin, diaminopyrimidines, sulfonamides, glycopeptide, and lipopeptide antibiotics). Mechanisms of antimicrobial resistance refer mainly to regulation of antibiotic transportation through bacterial membranes, alteration of the antibiotic target site, and enzymatic modifications resulting in antibiotic neutralization. Virulence factors that may affect antibiotic susceptibility profiles and confer drug resistance are also being discussed. Reports from cases of A. baumannii coinfection with SARS-CoV-2 during the COVID-19 pandemic in terms of resistance profiles and MDR genes have been investigated.

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“…This gram-negative bacterium is incredibly resistant to β-lactam antibiotics (i. e. penicillins, cephalosporins, carbapenems, monobactams, and others (i.e aminoglycosides, tetracyclines, fluoroquinolones, macrolides, lincosamides, streptogramin, polymyxins, amphenicols, oxazolidinones, rifamycins, fosfomycin, and diaminopyrimidine antibiotics). [3][4][5][6] A. baumannii resistance mechanisms refer mainly to the regulation of antibiotic transportation through bacterial membranes, alteration of the antibiotic target site, and enzymatic modifications resulting in antibiotic neutralization. [7] A. baumannii is one of the ESKAPE organisms (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, A. baumannii, Pseudomonas aeruginosa, and Enterobacter spp., [8] and according to the WHO report published in 2017, the ESKAPE group are multidrug-resistant pathogens for which new antibiotics are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

“…Carbapenemresistant A. baumannii is one of the critical priority pathogens that needs urgent research and development of new antibiotics. [9] While studying resistant bacteria, traditional drug discovery efforts have proven to be of limited use in replenishing our depleted arsenal of therapeutic antibiotics. [10] In addition, rapid progress in next-generation sequencing technologies has provided essential insights into drug discovery.…”

Section: Introductionmentioning

confidence: 99%

“…Several strains of A. baumannii are increasingly resistant to the most clinically available antibiotics. This gram‐negative bacterium is incredibly resistant to β‐lactam antibiotics (i. e. penicillins, cephalosporins, carbapenems, monobactams, and others (i.e aminoglycosides, tetracyclines, fluoroquinolones, macrolides, lincosamides, streptogramin, polymyxins, amphenicols, oxazolidinones, rifamycins, fosfomycin, and diaminopyrimidine antibiotics) [3–6] . A. baumannii resistance mechanisms refer mainly to the regulation of antibiotic transportation through bacterial membranes, alteration of the antibiotic target site, and enzymatic modifications resulting in antibiotic neutralization [7] .…”

Section: Introductionmentioning

confidence: 99%

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Inhibitor Assessment against the LpxC Enzyme of Antibiotic‐resistant Acinetobacter baumannii Using Virtual Screening, Dynamics Simulation, and in vitro Assays

Zoghlami

Oueslati

Basharat

et al. 2022

Molecular Informatics

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Background: Bacterial resistance is currently a significant global public health problem. Acinetobacter baumannii has been ranked in the list of the World Health Organization as the most critical and priority pathogen for which new antibiotics are urgently needed. In this context, computational methods play a central role in the modern drug discovery process. The purpose of the current study was to identify new potential therapeutic molecules to neutralize MDR A. baumannii bacteria. Methods: A total of 3686 proteins retrieved from the A. baumannii proteome were subjected to subtractive proteomic analysis to narrow down the spectrum of drug targets. The SWISS-MODEL server was used to perform a 3D homology model of the selected target protein. The SAVES server was used to evaluate the overall quality of the model. A dataset of 74500 analogues retrieved from the PubChem database was docked with LpxC using the AutoDock software. Results: In this study, we predicted a putative new inhibitor for the Lpxc enzyme of A. baumannii. The LpxC enzyme was selected as the most appropriate drug target for A. baumannii. According to the virtual screening results, N-[(2S)-3amino-1-(hydroxyamino)-1-oxopropan-2-yl]-4-(4-bromophenyl) benzamide (CS250) could be a promising drug candidate targeting the LpxC enzyme. This molecule shows polar interactions with six amino acids and non-polar interactions with eight other residues. In vitro experimental validation was performed through the inhibition assay. Conclusion:To the best of our knowledge, this is the first study that suggests CS250 as a promising inhibitory molecule that can be exploited to target this gram-negative pathogen.

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Distribution of carbapenem resistant Acinetobacter baumannii with blaADC-30 and induction of ADC-30 in response to beta-lactam antibiotics

Cited by 20 publications

References 43 publications

Genetic characterization of extended-spectrum β-Lactamase- and carbapenemase-producing Escherichia coli isolated from Egyptian hospitals and environments

Genetic characterization of extended-spectrum β-Lactamase- and carbapenemase-producing Escherichia coli isolated from Egyptian hospitals and environments

Acinetobacter baumannii Antibiotic Resistance Mechanisms

Inhibitor Assessment against the LpxC Enzyme of Antibiotic‐resistant Acinetobacter baumannii Using Virtual Screening, Dynamics Simulation, and in vitro Assays

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