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ABSTRACT:
PROVIDER: PRJNA1180724 | ENA |
REPOSITORIES: ENA
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Project description:Carbapenem-resistant Acinetobacter baumannii (CRAB) is a recognized nosocomial pathogen with limited therapeutics options. Lactic acid bacteria (LAB) constitute a promising therapeutic alternative. Here we aimed to study the antibacterial properties of a collection of LAB strains using phenotypic and transcriptomic analysis against A. baumannii clinical strains. One strain, Lacticaseibacillus rhamnosus CRL 2244, exerts a strong inhibitory capacity on A. baumannii with a strong killing activity. Scanning electron microscopy images showed changes in the morphology of A. baumannii with an increase formation of outer membrane vesicles. Significant changes in the expression levels a wide variety of genes were observed. Interestingly, most of the modified genes were involved in metabolic pathway known to be associated with bacterial survival. The paa operon, Hut system, and fatty acid degradation were some of the pathways that have been induced. The data reveals the impact of Lcb. rhamnosus CRL 2244 on A. baumannii response, resulting in bacterial stress and subsequent cell death. These findings highlight the antibacterial properties of Lcb. rhamnosus CRL 2244 and its potential as an alternative or complementary strategy for treating infections. Further exploration and development of this LAB as a treatment option could provide valuable alternatives for combating CRAB infections.
2023-09-14 | GSE236782 | GEO
Project description:Acinetobacter baumannii is an emerging nosocomial pathogen that causes severe infections such as pneumonia or blood stream infections. As the incidence of multidrug-resistant A. baumannii infections in intensive care units increases, the pathogen is considered of greater clinical concern. Little is known about the molecular interaction of A. baumannii with its host yet. In order to study the host cell response upon A. baumannii infection, a complexome analysis was performed. For this, we identified a virulent ( A. baumannii 2778) and a non virulent (A. baumannii 1372) clinical isolate of genetic similarity > 95 % (both isolates from IC 2 harboring OXA 23). HUVECs were infected with each strain and enriched mitochondrial fraction was used for complexome profiling. Complexome analysis identified dramatic reduction of mitochondrial protein complexes in the strain of greater virulence.
2023-04-10 | PXD035235 | Pride
Project description:Objectives: Carbapenem-resistant Acinetobacter baumannii (CRAB) are one of the most difficult pathogen to treat. The only drug recently approved by the FDA that is active against CRAB is cefiderocol. However, recent studies have shown higher all-cause mortality rate in the group of patients treated with cefiderocol, that may be due to heteroresistance, a phenotype characterized by the survival of a small proportion of cells in a population seemingly isogenic. Previous studies showed that adding human fluids to CRAB cultures can lead to CFDC heteroresistance. To better understand the nature of this phenomenon, we carried out molecular and phenotypic analyses of CRAB heteroresistant bacterial subpopulations. Methods: The CRAB strain AMA40 was cultured in the presence of cefiderocol and human pleural fluid (HPF) to isolate heteroresistant variants. Two of them, AMA40 IHC_1 and IHC_2, were subjected to whole genome sequencing and transcriptomic analysis to identify the mutations and transcriptomic changes responsible for the development of cefiderocol resistance. The impact of mutations on the pharmacodynamic activity of cefiderocol was assessed by susceptibility testing, EDTA and Boronic acid inhibition analysis, biofilm formation, and static time-kill assays. Results: Variants AMA40 IHC_1 and IHC_2 had 53 mutations, forty of which were common to both heteroresistant strains. None of the mutations are located inside genes associated with iron-uptake systems or β-lactam resistance. However, pipA, a gene associated with iron homeostasis in other species, was mutated in heteroresistant strains. Transcriptomic analyses revealed modifications in levels of expression of genes associated with antibiotic resistance. The blaNDM-1, blaADC-2, pbp3, and pbp1 were expressed at higher levels. At the same time, the carO and ompA genes’ expression was reduced. Collateral resistance to amikacin was observed in the heteroresistant variants. Static time-kill assays showed that when CA-MHB was supplemented with human serum albumin, the main protein component of HPF, cefiderocol killing activity was considerably reduced in all three strains. Conclusions: We conclude that heteroresistance to cefiderocol in CRAB, when exposed to fluids containing high HSA, is caused by mutations and modifications in the expression of genes associated with resistance to β-lactams.
2023-03-31 | E-MTAB-12444 | biostudies-arrayexpress
Project description:Carbapenem-resistant Acinetobacter baumannii (CRAb) is an urgent public health threat, according to the CDC. This pathogen has few treatment options and causes severe nosocomial infections with >50% fatality rate. Although previous studies have examined the proteome of CRAb, there have been no focused analyses of dynamic changes to β-lactamase expression that may occur due to drug exposure. Here, we present our initial proteomic study of variation in β-lactamase expression that occurs in CRAb with different β-lactam antibiotics. Briefly, drug resistance to Ab (ATCC 19606) was induced by the administration of various classes of β-lactam antibiotics, and the cell-free supernatant was isolated, concentrated, separated by SDS-PAGE, digested with trypsin, and identified by label-free LC-MS-based quantitative proteomics. Thirteen proteins were identified and evaluated using a 1789 sequence database of Ab β-lactamases from UniProt, the majority of which were Class C β-lactamases (≥80%). Importantly, different antibiotics, even those of the same class (e.g. penicillin and amoxicillin), induced non-equivalent responses comprising various isoforms of Class C and D serine-β-lactamases, resulting in unique resistomes. These results open the door to a new approach of analyzing and studying the problem of multi-drug resistance in bacteria that rely strongly on β-lactamase expression.
2023-07-20 | PXD042336 | Pride
Project description:Miseq Whole Genome Sequencing of three extensively-drug-resistant Acinetobacter baumannii isolated from intensive care units
| PRJEB30466 | ENA
Project description:Carbapenem-resistant Acinetobacter baumannii (CRAB) is a Priority 1 (Critical) pathogen urgently requiring new antibiotics. Polymyxins are a last-line option against CRAB-associated infections. This transcriptomic study utilized a CRAB strain to investigate mechanisms of bacterial killing with polymyxin B, colistin, colistin B and colistin/sulbactam combination therapy. After 4 h of 2 mg/L polymyxin monotherapy, all polymyxins exhibited common modes of action which primarily involved disruption to amino acid and fatty acid metabolism. Of the three monotherapies, polymyxin B induced the greatest number of differentially expressed genes (DEGs), including for genes involved with fatty acid metabolism. Gene disturbances with colistin and colistin B were highly similar (89% common genes for colistin B), though effects on gene expression were generally lower (0-1.5-fold in most cases) with colistin B. Colistin alone (2 mg/L) or combined with sulbactam (64 mg/L) resulted in rapid membrane disruption as early as 1 h. Transcriptomic analysis of this combination revealed the effects were driven by colistin and included disturbances in fatty acid synthesis and catabolism and inhibition of nutrient uptake. Combination therapy produced substantially higher fold changes in 72% of DEGs shared with monotherapy, resulting in substantially greater reductions in fatty acid biosynthesis and increases in biofilm, cell wall and phospholipid synthesis. This indicates synergistic bacterial killing with the colistin/sulbactam combination results from a systematic increase in perturbation of many genes associated with bacterial metabolism. These mechanistic insights enhance our understanding of bacterial responses to polymyxin mono- and combination therapy and will assist to optimize polymyxin use in patients. Carbapenem-resistant Acinetobacter baumannii (CRAB) is a Priority 1 (Critical) pathogen urgently requiring new antibiotics. Polymyxins are a last-line option against CRAB-associated infections. This transcriptomic study utilized a CRAB strain to investigate mechanisms of bacterial killing with polymyxin B, colistin, colistin B and colistin/sulbactam combination therapy. After 4 h of 2 mg/L polymyxin monotherapy, all polymyxins exhibited common modes of action which primarily involved disruption to amino acid and fatty acid metabolism. Of the three monotherapies, polymyxin B induced the greatest number of differentially expressed genes (DEGs), including for genes involved with fatty acid metabolism. Gene disturbances with colistin and colistin B were highly similar (89% common genes for colistin B), though effects on gene expression were generally lower (0-1.5-fold in most cases) with colistin B. Colistin alone (2 mg/L) or combined with sulbactam (64 mg/L) resulted in rapid membrane disruption as early as 1 h. Transcriptomic analysis of this combination revealed the effects were driven by colistin and included disturbances in fatty acid synthesis and catabolism and inhibition of nutrient uptake. Combination therapy produced substantially higher fold changes in 72% of DEGs shared with monotherapy, resulting in substantially greater reductions in fatty acid biosynthesis and increases in biofilm, cell wall and phospholipid synthesis. This indicates synergistic bacterial killing with the colistin/sulbactam combination results from a systematic increase in perturbation of many genes associated with bacterial metabolism. These mechanistic insights enhance our understanding of bacterial responses to polymyxin mono- and combination therapy and will assist to optimize polymyxin use in patients.
2023-07-01 | GSE218219 | GEO
Project description:Acinetobacter baumannii is a Gram-negative pathogen that has emerged as one of the most troublesome pathogens for health care institutions globally. Bacterial quorum sensing (QS) is a process of cell-to-cell communication that relies on the production, secretion and detection of autoinducer (AI) signals to share information about cell density and regulate gene expression accordingly. The molecular and genetic basis of Acinetobacter baumannii virulence remains poorly understood. Therefore, the contribution of the abaI/abaR quorum sensing system to growth characteristics, morphology, biofilm formation, resistance, motility and virulence of Acinetobacter baumannii was studied in detail. RNA-seq analysis indicated that genes involved in various aspects of energy production and conversion, Valine, leucine and isoleucine degradation and lipid transport and metabolism are associated with bacterial pathogenicity. Our work provides a new insight into abaI/abaR quorum sensing system effects pathogenicity in A. baumannii. We propose that targeting the AHL synthase enzyme abaI could provide an effective strategy for attenuating virulence. On the contrary, interdicting the autoinducer synthase–receptor abaR elicits unpredictable consequences, which may lead to enhanced bacterial virulence.
2021-04-28 | GSE173396 | GEO