Dataset Information

Profiling of Potential Antibacterial Compounds of Lactic Acid Bacteria against Extremely Drug Resistant (XDR) Acinetobacter baumannii.

ABSTRACT: A total of 20 of isolates of lactic acid bacteria (LAB) were selected and screened for antagonistic activity against clinical strains of 30 clinical isolates of extremely drug-resistant (XDR) Acinetobacter baumannii using the well diffusion assay method. Results showed that 50% of the highly LAB strains possessed inhibitory activity against (up to 66%) of the XDR A. baumannii strains tested. The supernatant of the twenty LAB strains was subjected to gas chromatography mass spectrometry (GCMS) revealed that the common compound found in the active isolates against XDR A. baumannii was 3-Isobutyl-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione, a known potential diketopiperazine group. The molecular docking study against potential antibacterial targets with selected ligands was performed to predict the binding mode of interactions, which is responsible for antibacterial activity. The docking analysis of the potent compounds supported the potential antibacterial activity exhibiting high inhibition constant and binding affinity in silico.

SUBMITTER: Yap PC

PROVIDER: S-EPMC8003687 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Profiling of Potential Antibacterial Compounds of Lactic Acid Bacteria against Extremely Drug Resistant (XDR) Acinetobacter baumannii.

Yap Phui-Chyng PC Ayuhan Noorfazlin N Woon Jia Jie JJ Teh Cindy Shuan Ju CSJ Lee Vannajan Sanghiran VS Azman Adzzie Shazleen AS AbuBakar Sazaly S Lee Hai Yen HY

Molecules (Basel, Switzerland) 20210319 6

A total of 20 of isolates of lactic acid bacteria (LAB) were selected and screened for antagonistic activity against clinical strains of 30 clinical isolates of extremely drug-resistant (XDR) Acinetobacter baumannii using the well diffusion assay method. Results showed that 50% of the highly LAB strains possessed inhibitory activity against (up to 66%) of the XDR A. baumannii strains tested. The supernatant of the twenty LAB strains was subjected to gas chromatography mass spectrom ...[more]

PMID: 33808805

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Project description:Nosocomial infections caused by extensively drug-resistant (XDR) or Pan-Drug resistant (PDR) Acinetobacter (A.) baumannii have recently increased dramatically creating a medical challenge as therapeutic options became very limited. The aim of our study was to investigate the antibiotic-resistance profiles and evaluate the various combinations of ciprofloxacin (CIP) or levofloxacin (LEV) with antimicrobial agents and non-antimicrobial agents to combat antimicrobial resistance of XDR A. baumannii. A total of 100 (6.25%) A. baumannii clinical isolates were recovered from 1600 clinical specimens collected from hospitalized patients of two major university hospitals in Upper Egypt. Antimicrobial susceptibility tests were carried out according to CLSI guidelines. Antimicrobial susceptibility testing of the respective isolates showed a high percentage of bacterial resistance to 19 antimicrobial agents ranging from 76 to99%. However, a lower percentage of resistance was observed for only colistin (5%) and doxycycline (57%). The isolates were categorized as PDR (2; 2%), XDR (68; 68%), and multi-drug resistant (MDR) (30; 30%). Genotypic analysis using ERIC-PCR on 2 PDR and 32 selected XDR isolates showed that they were not clonal. Combinations of CIP or LEV with antibiotics (including, ampicillin, ceftriaxone, amikacin, or doxycycline) were tested on these A. baumannii non-clonal isolates using standard protocols where fractional inhibitory concentrations (-FICs) were calculated. Results of the respective combinations showed synergism in 23.5%, 17.65%, 32.35%, 17.65% and 26.47%, 8.28%, 14.71%, 26.47%, of the tested isolates, respectively. CIP or LEV combinations with either chlorpromazine (CPZ) 200 μg/ml, propranolol (PR) in two concentrations, 0.5 mg/ml and 1.0 mg/ml or diclofenac (DIC) 4 mg/ml were carried out and the MIC decrease factor (MDF) of each isolate was calculated and results showed synergism in 44%, 50%, 100%, 100% and 94%, 85%, 100%, 100%, of the tested isolates, respectively. In conclusion, combinations of CIP or LEV with CPZ, PR, or DIC showed synergism in most of the selected PDR and XDR A. baumannii clinical isolates. However, these combinations have to be re-evaluated in vivo using appropriate animal models infected by XDR- or PDR- A. baumannii.

Project description:Acinetobacter baumannii is an opportunistic pathogen primarily associated with multidrug-resistant nosocomial infections, for which polymyxins are the last-resort antibiotics. This study investigated carbapenem-resistant A. baumannii strains exhibiting an extensively drug-resistant (XDR) phenotype, including four isolates considered locally pan drug-resistant (LPDR), isolated from inpatients during an outbreak at a teaching hospital in Brazil. ApaI DNA macrorestriction followed by PFGE clustered the strains in three pulsotypes, named A to C, among carbapenem-resistant A. baumannii strains. Pulsotypes A and B clustered six polymyxin-resistant A. baumannii strains. MLST analysis of representative strains of pulsotypes A, B, and C showed that they belong, respectively, to sequence types ST1 (clonal complex, CC1), ST79 (CC79), and ST903. Genomic analysis of international clones ST1 and ST79 representative strains predicted a wide resistome for β-lactams, aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole, with bla OXA-23 and bla OXA-72 genes encoding carbapenem resistance. Amino acid substitutions in PmrB (Thr232Ile or Pro170Leu) and PmrC (Arg125His) were responsible for polymyxin resistance. Although colistin MICs were all high (MIC ≥ 128 mg/L), polymyxin B MICs varied; strains with Pro170Leu substitution in PmrB had MICs > 128 mg/L, while those with Thr232Ile had lower MICs (16-64 mg/L), irrespective of the clone. Although the first identified polymyxin-resistant A. baumannii strain belonged to ST79, the ST1 strains were endemic and caused the outbreak most likely due to polymyxin B use. The genome comparison of two ST1 strains from the same patient, but one susceptible and the other resistant to polymyxin, revealed mutations in 28 ORFs in addition to pmrBC. The ORF codifying an acyl-CoA dehydrogenase has gained attention due to its fatty acid breakdown and membrane fluidity involvement. However, the role of these mutations in the polymyxin resistance mechanism remains unknown. To prevent the dissemination of XDR bacteria, the hospital infection control committee implemented the patient bathing practice with a 2% chlorhexidine solution, a higher concentration than all A. baumannii chlorhexidine MICs. In conclusion, we showed the emergence of polymyxin resistance due to mutations in the chromosome of the carbapenem-resistant A. baumannii ST1, a high-risk global clone spreading in this hospital.

Dataset Information

Profiling of Potential Antibacterial Compounds of Lactic Acid Bacteria against Extremely Drug Resistant (XDR) Acinetobacter baumannii.

Publications

Profiling of Potential Antibacterial Compounds of Lactic Acid Bacteria against Extremely Drug Resistant (XDR) <i>Acinetobacter baumannii</i>.

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