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Pathogens (Basel, Switzerland) Jan 2024spp. are intrinsically resistant to multiple antibiotics and can also acquire resistance to those commonly used for the treatment of respiratory infections, especially...
spp. are intrinsically resistant to multiple antibiotics and can also acquire resistance to those commonly used for the treatment of respiratory infections, especially in patients with cystic fibrosis. The aim of this study was to perform the genetic and biochemical characterization of AXC-2 from and to analyze all available AXC variants. Steady-state kinetic parameters were determined on a purified AXC-2 enzyme. It exhibited higher catalytic efficiencies towards amino-penicillins and older cephalosporins, while carbapenems behaved as poor substrates. Phylogenetic analysis of all variants available in the NCBI was conducted. AXC was encoded in almost all genomes, whereas it was only found in 30% of . AXC-1 was prevalent among . AXC variants were clustered in two main groups, correlating with the species. No association could be established between the presence of variants and a specific lineage of ; however, a proportion of AXC-1-producing isolates corresponded to ST 182 and ST 447. In conclusion, this study provides valuable insights into the genetic context and kinetic properties of AXC-2, identified in . It also provides a thorough description of all AXC variants and their association with species and various lineages.
PubMed: 38392853
DOI: 10.3390/pathogens13020115 -
Viruses Jul 2023species colonization of Cystic Fibrosis respiratory airways is an increasing concern. Two adult patients with Cystic Fibrosis colonized by CF418 or CF116 experienced...
species colonization of Cystic Fibrosis respiratory airways is an increasing concern. Two adult patients with Cystic Fibrosis colonized by CF418 or CF116 experienced fatal exacerbations. spp. are naturally resistant to several antibiotics. Therefore, phages could be valuable as therapeutics for the control of . In this study, thirteen lytic phages were isolated and characterized at the morphological and genomic levels for potential future use in phage therapy. They are presented here as the Kumeyaay phage collection. Six distinct phage genome clusters were identified based on a comprehensive phylogenetic analysis of the Kumeyaay collection as well as the publicly available phages. The infectivity of all phages in the Kumeyaay collection was tested in 23 clinical isolates; 78% of these isolates were lysed by at least one phage. A cryptic prophage was induced in CF418 when infected with some of the lytic phages. This prophage genome was characterized and is presented as phage CF418-P1. Prophage induction during lytic phage preparation for therapy interventions require further exploration. Large-scale production of phages and removal of endotoxins using an octanol-based procedure resulted in a phage concentrate of 1 × 10 plaque-forming units per milliliter with an endotoxin concentration of 65 endotoxin units per milliliter, which is below the Food and Drugs Administration recommended maximum threshold for human administration. This study provides a comprehensive framework for the isolation, bioinformatic characterization, and safe production of phages to kill spp. in order to potentially manage Cystic Fibrosis (CF) pulmonary infections.
Topics: Adult; Humans; Bacteriophages; Cystic Fibrosis; Phylogeny; Achromobacter; Achromobacter denitrificans; Prophages; Endotoxins
PubMed: 37632008
DOI: 10.3390/v15081665 -
Antimicrobial Agents and Chemotherapy Jul 2023We conducted antimicrobial susceptibility testing of 267 isolates for 16 antibiotics from 2017 to 2022. The highest susceptibility was found for...
We conducted antimicrobial susceptibility testing of 267 isolates for 16 antibiotics from 2017 to 2022. The highest susceptibility was found for piperacillin-tazobactam (70%) and ceftazidime-avibactam (62%). Between 30% and 49% of strains were susceptible to tigecycline, ceftazidime, and meropenem. We applied species-specific Achromobacter xylosoxidans breakpoints for piperacillin-tazobactam, meropenem, and trimethoprim-sulfamethoxazole and EUCAST pharmacokinetic/pharmacodynamic (PK/PD) breakpoints for the others. A. xylosoxidans was the most frequently isolated species, followed by Achromobacter insuavis and Achromobacter ruhlandii.
Topics: Humans; Meropenem; Cystic Fibrosis; Microbial Sensitivity Tests; Anti-Bacterial Agents; Achromobacter; Piperacillin; Tazobactam
PubMed: 37310234
DOI: 10.1128/aac.00379-23 -
Microbiology Spectrum Aug 2023is a genus of Gram-negative rods, which can cause persistent airway infections in people with cystic fibrosis (CF). The knowledge about virulence and clinical...
is a genus of Gram-negative rods, which can cause persistent airway infections in people with cystic fibrosis (CF). The knowledge about virulence and clinical implications of is still limited, and it is not fully established whether infections contribute to disease progression or if it is a marker of poor lung function. The most commonly reported species in CF is A. xylosoxidans. While other spp. are also identified in CF airways, the currently used Matrix-Assisted Laser Desorption/Ionization Time Of Flight Mass Spectrometry (MALDI-TOF MS) method in routine diagnostics cannot distinguish between species. Differences in virulence between species have consequently not been well studied. In this study, we compare phenotypes and proinflammatory properties of A. xylosoxidans, , , and using models. Bacterial supernatants were used to stimulate CF bronchial epithelial cells and whole blood from healthy individuals. Supernatants from the well-characterized CF-pathogen Pseudomonas aeruginosa were included for comparison. Inflammatory mediators were analyzed with ELISA and leukocyte activation was assessed using flow cytometry. The four species differed in morphology seen in scanning electron microscopy (SEM), but there were no observed differences in swimming motility or biofilm formation. Exoproducts from all species except caused significant IL-6 and IL-8 secretion from CF lung epithelium. The cytokine release was equivalent or stronger than the response induced by P. aeruginosa. All species activated neutrophils and monocytes in a lipopolysaccharide (LPS)-independent manner. Our results indicate that exoproducts of the four included species do not differ consistently in causing inflammatory responses, but they are equally or even more capable of inducing inflammation compared with the classical CF pathogen P. aeruginosa. Achromobacter xylosoxidans is an emerging pathogen among people with cystic fibrosis (CF). Current routine diagnostic methods are often unable to distinguish A. xylosoxidans from other species, and the clinical relevance of different species is still unknown. In this work, we show that four different species relevant to CF evoke similar inflammatory responses from airway epithelium and leukocytes , but they are all equally or even more proinflammatory compared to the classic CF-pathogen Pseudomonas aeruginosa. The results suggest that species are important airway pathogens in CF, and that all species are relevant to treat.
Topics: Humans; Achromobacter; Cystic Fibrosis; Gram-Negative Bacterial Infections; Achromobacter denitrificans; Lung
PubMed: 37284754
DOI: 10.1128/spectrum.00195-23 -
BMC Microbiology Jun 2023Klebsiella pneumoniae is one of the main pathogens of clinical isolation and nosocomial infections, as K. pneumoniae show broad-spectrum resistance to β-lactam and...
BACKGROUND
Klebsiella pneumoniae is one of the main pathogens of clinical isolation and nosocomial infections, as K. pneumoniae show broad-spectrum resistance to β-lactam and carbapenem antibiotics. It is emerging clinical need for a safe and effective drug to anti-K. pneumoniae. At present, Achromobacter mainly focused on its degradation of petroleum hydrocarbons, polycyclic aromatic hydrocarbons, assisting insects to decompose, degrade heavy metals and utilize organic matter, but there were few reports on the antibacterial activity of the secondary metabolites of Achromobacter.
RESULTS
In this study, a strain WA5-4-31 from the intestinal tract of Periplaneta americana exhibited strong activity against K. Pneumoniae through preliminary screening. The strain was determined to be Achromobacter sp. through the morphological characteristics, genotyping and phylogenetic tree analysis, which is homologous to Achromobacter ruhlandii by 99%, its accession numbe in GenBank at National Center for Biotechnology Information (NCBI) is MN007235, and its deposit number was GDMCC NO.1.2520. Six compounds (Actinomycin D, Actinomycin X2, Collismycin A, Citrinin, Neoechinulin A and Cytochalasin E) were isolated and determined by activity tracking, chemical separation, nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis. Among them, Actinomycin D, Actinomycin X2, Collismycin A, Citrinin and Cytochalasin E showed a good effect on anti-K. pneumoniae, with MIC values of 16-64 µg/mL.
CONCLUSIONS
The study reported Achromobacter, which was from the intestinal tract of Periplaneta americana with the activity against K. Pneumoniae, can produce antibacterial compounds for the first time. It lays the foundation for development of secondary metabolites of insect intestinal microorganisms.
Topics: Animals; Periplaneta; Dactinomycin; Citrinin; Klebsiella pneumoniae; Phylogeny; Secondary Metabolism; Anti-Bacterial Agents; Achromobacter; Intestines; Klebsiella Infections; Microbial Sensitivity Tests; beta-Lactamases
PubMed: 37277707
DOI: 10.1186/s12866-023-02909-7