Heliyon, Journal Year: 2024, Volume and Issue: 11(1), P. e41487 - e41487
Published: Dec. 25, 2024
Language: Английский
Microbial Genomics, Journal Year: 2025, Volume and Issue: 11(2)
Published: Feb. 19, 2025
Acinetobacter baumannii is a nosocomial pathogen associated with various infections, including urinary tract infections (UTIs). In the course of an infection, A. known to rapidly become resistant antibiotic therapy, but much less about possible adaptation without pressure. Through retrospective study, we investigated within-host genetic diversity during subclinical 5-year UTI in animal-patient after withdrawal colistin treatment. We conducted whole-genome sequencing and phenotypic assays on 17 clonally related isolates from Sequence Type 25 lineage. Phylogenomic analysis revealed their proximity animal human strains same country suggesting zoonotic transmission (France). this case presented variations genome sizes nucleotide sequences. Over underwent reduction through insertion sequence (IS) recombination, phage excision or plasmid curing. Alongside global reduction, observed expansion IS17, initially located endogenous large plasmid. Genetic were mainly biofilm formation metabolism genes. repeated affecting three genes two adhesion operons weak biofilm-forming capacity. Conversely, only metabolic recurrently affected, indicated rather stable profile between minor adaptations its host. Lastly, overall decreased resistance - expected absence treatment contrasted conserved due pmrB mutation among isolates.
Language: Английский
Citations
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Biological and Pharmaceutical Bulletin, Journal Year: 2025, Volume and Issue: 48(3), P. 213 - 221
Published: Feb. 28, 2025
The emergence of drug-resistant bacteria has posed a significant problem in medical institutions worldwide. Colistin, which targets lipopolysaccharide (LPS), serves as last-resort antimicrobial agent against multidrug-resistant Gram-negative bacteria. Nevertheless, Acinetobacter baumannii, pathogen with worldwide prevalence resistance, been reported to develop resistance colistin frequently. In this review, we discuss how A. baumannii acquires colistin, focusing on modification well loss LPS present its outer membrane, is the primary mechanism baumannii's colistin. Basic and clinical insights regarding have discussed isolation. Therefore, relationship between these 2 mechanisms terms frequency fitness genetic mutations based from basic studies settings. We concluded that understanding detailed drug requires comprehensive both effects selection pressure. Finally, highlight importance promoting research science perspectives.
Language: Английский
Citations
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Biochemistry, Journal Year: 2025, Volume and Issue: unknown
Published: March 8, 2025
Two-component systems serve as ubiquitous communication modules that enable bacteria to detect and respond various stimuli by regulating cellular processes such growth, viability, and, most notably, antimicrobial resistance. Classical two-component consist of two proteins: an initial membrane-bound sensor histidine kinase a DNA-binding response regulator induces the appropriate within cell. Numerous studies have implicated PmrAB system in facilitating resistance last-resort antibiotic polymyxin E (colistin) Acinetobacter baumannii. As initiators signaling pathways elicit resistance, kinases present ideal targets for developing adjuvant drugs. Despite this, due nature PmrB, vitro on been predominantly limited PmrA. In this work, we counter these limitations producing recombinant truncation cytosolic portion PmrB (PmrBc) retains its ATP binding, autophosphorylation, phosphotransfer functions. Subsequently, vivo phosphorylation assays using protein construct allowed evaluation five compounds (IMD-0354, NDM-265, NDM-455, NDM-463, NDM-497) act PmrBc inhibitors capable preventing autophosphorylation independently. These shown eliminate colistin vivo. Finally, results, paired with mass spectrometry proteolysis investigations, enabled us determine mechanism action well their likely binding site ATP-lid PmrB.
Language: Английский
Citations
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Microbiology Spectrum, Journal Year: 2024, Volume and Issue: unknown
Published: Sept. 17, 2024
ABSTRACT In vivo imaging of bacterial infection models enables noninvasive and temporal analysis individuals, enhancing our understanding infectious disease pathogenesis. Conventional in methods for involve the insertion luciferase LuxCDABE into genome, followed by using an expensive ultrasensitive charge-coupled device (CCD) camera. However, issues such as limited light penetration body lack versatility have been encountered. We focused on near-infrared (NIR) light, which penetrates effectively, attempted to establish method evaluate number lung-colonizing bacteria during course pneumonia. This was achieved employing a novel versatile system that combines plasmid-expressing firefly bacteria, NIR substrate, inexpensive, scientific complementary metal-oxide semiconductor (sCMOS) The D-luciferin derivative “TokeOni,” capable emitting bioluminescence, utilized mouse lung model Acinetobacter baumannii , opportunistic pathogen causes pneumonia is concern due drug resistance. TokeOni exhibited highest sensitivity detecting colonizing lungs compared with other detection systems LuxCDABE, enabling monitoring changes numbers over time assessment antimicrobial agent efficacy. Additionally, it effective A. clinical isolates Klebsiella pneumoniae . results this study are expected be used animal diseases assessing efficacy therapeutic agents IMPORTANCE traditionally relied upon average assessments involving numerous meaning they do not directly reflect pathology individual. Moreover, recent years, ethical concerns resulted demand reduce animals models. Although offers approach longitudinally evaluating pathogenesis individual animals, standardized has yet established. To knowledge, first develop highly pulmonary quantification utilizing luminescence, plasmid-mediated expression Our research holds promise useful tool drugs diseases.
Language: Английский
Citations
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Pathogens, Journal Year: 2024, Volume and Issue: 13(12), P. 1049 - 1049
Published: Nov. 28, 2024
The emergence of antibiotic-resistant Acinetobacter baumannii (A. baumannii) is a pressing threat in clinical settings. Colistin currently widely used treatment for multidrug-resistant A. baumannii, serving as the last line defense. However, reports colistin-resistant strains have emerged, underscoring urgent need to develop alternative medications combat these serious pathogens. To resist colistin, has developed several mechanisms. These include loss outer membrane lipopolysaccharides (LPSs) due mutation LPS biosynthetic genes, modification lipid A (a constituent LPSs) structure through addition phosphoethanolamine (PEtN) moieties component by overexpression chromosomal pmrCAB operon genes and eptA gene, or acquisition plasmid-encoded mcr horizontal gene transfer. Other resistance mechanisms involve alterations permeability porins, expulsion colistin efflux pumps, heteroresistance. In response rising researchers various strategies, including antibiotic combination therapy, adjuvants potentiate activity, repurposing existing drugs, antimicrobial peptides, nanotechnology, photodynamic CRISPR/Cas, phage therapy. While many strategies shown promise vitro vivo, further trials are necessary ensure their efficacy widen applications. Ongoing research essential identifying most effective therapeutic manage baumannii. This review explores genetic underlying assesses potential options this challenging pathogen.
Language: Английский
Citations
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Heliyon, Journal Year: 2024, Volume and Issue: 11(1), P. e41487 - e41487
Published: Dec. 25, 2024
Language: Английский
Citations
0