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Case Reports in Dermatology 2023Green nail syndrome (GNS) is a persistent greenish pigmentation of the nail plate, originally described in 1944 by Goldman and Fox, due to infection. Recently,...
Green nail syndrome (GNS) is a persistent greenish pigmentation of the nail plate, originally described in 1944 by Goldman and Fox, due to infection. Recently, pulmonary co-infection of and spp. has been described in patients with cystic fibrosis. is a multidrug-resistant (MDR) pathogen involved in lung and soft tissue skin infections. Both and are mainly found in humid environments or in water. There are no recognized co-infections due to and in the skin and appendages. We describe two cases of GNS, the first due to associated with ; the other due to MDR , both successfully treated with topical ozenoxacin 1% cream daily for 12 weeks. The clinical management of GNS can be confusing, especially when the bacterial culture result is inconsistent or when non- bacteria are isolated. In our case, due to the co-infection of and spp., local treatment with ozenoxacin - the first nonfluorinated quinolone - could be a safe and effective treatment in case of MDR nail infections. Further studies are required to evaluate clinical isolation from nail infections and the co-presence of and .
PubMed: 38023344
DOI: 10.1159/000533923 -
Inflammation Research : Official... Dec 2022Our research aimed to investigate the role of CD14 in pulmonary infection by Achromobacter xylosoxidans in an experimental murine model.
OBJECTIVE AND DESIGN
Our research aimed to investigate the role of CD14 in pulmonary infection by Achromobacter xylosoxidans in an experimental murine model.
METHODS
C57Bl/6 or CD14-deficient mice were infected intratracheally with non-lethal inoculum of A. xylosoxidans. At times 1, 3 and 7 days after infection, lungs, bronchoalveolar lavage and blood were collected. CD14 gene expression was determined by RT-PCR. The bacterial load in the lungs was assessed by counting colony forming units (CFU). Cytokines, chemokines, lipocalin-2 and sCD14 were quantified by the ELISA method. Inflammatory infiltrate was observed on histological sections stained with HE, and leukocyte subtypes were assessed by flow cytometry. In another set of experiments, C57Bl/6 or CD14-deficient mice were inoculated with lethal inoculum and the survival rate determined.
RESULTS
CD14-deficient mice are protected from A. xylosoxidans-induced death, which is unrelated to bacterial load. The lungs of CD14-deficient mice presented a smaller area of tissue damage, less neutrophil and macrophage infiltration, less pulmonary edema, and a lower concentration of IL-6, TNF-α, CXCL1, CCL2 and CCL3 when compared with lungs of C57Bl/6 mice. We also observed that A. xylosoxidans infection increases the number of leukocytes expressing mCD14 and the levels of sCD14 in BALF and serum of C57Bl/6-infected mice.
CONCLUSIONS
In summary, our data show that in A. xylosoxidans infection, the activation of CD14 induces intense pulmonary inflammatory response resulting in mice death.
Topics: Animals; Mice; Achromobacter denitrificans; Lipopolysaccharide Receptors; Lung; Mice, Inbred C57BL; Pneumonia; Tumor Necrosis Factor-alpha; Gram-Negative Bacterial Infections
PubMed: 36280620
DOI: 10.1007/s00011-022-01641-8 -
Scientific Reports Apr 2016Achromobacter xylosoxidans, an opportunistic pathogen, is responsible for various nosocomial and community-acquired infections. We isolated phiAxp-3, an N4-like...
Achromobacter xylosoxidans, an opportunistic pathogen, is responsible for various nosocomial and community-acquired infections. We isolated phiAxp-3, an N4-like bacteriophage that infects A. xylosoxidans, from hospital waste and studied its genomic and biological properties. Transmission electron microscopy revealed that, with a 67-nm diameter icosahedral head and a 20-nm non-contractile tail, phiAxp-3 has features characteristic of Podoviridae bacteriophages (order Caudovirales). With a burst size of 9000 plaque-forming units and a latent period of 80 min, phiAxp-3 had a host range limited to only four A. xylosoxidans strains of the 35 strains that were tested. The 72,825 bp phiAxp-3 DNA genome, with 416-bp terminal redundant ends, contains 80 predicted open reading frames, none of which are related to virulence or drug resistance. Genome sequence comparisons place phiAxp-3 more closely with JWAlpha and JWDelta Achromobacter phages than with other N4 viruses. Using proteomics, we identified 25 viral proteins from purified phiAxp-3 particles. Notably, investigation of the phage phiAxp-3 receptor on the surface of the host cell revealed that lipopolysaccharide serves as the receptor for the adsorption of phage phiAxp-3. Our findings advance current knowledge about A. xylosoxidans phages in an age where alternative therapies to combat antibiotic-resistant bacteria are urgently needed.
Topics: Bacteriophages; Computational Biology; DNA Replication; Gene Order; Genes, Viral; Genome, Viral; Genomics; Host Specificity; Hydrogen-Ion Concentration; Molecular Sequence Annotation; Phylogeny; Receptors, Virus; Temperature; Transcription, Genetic; Virion
PubMed: 27094846
DOI: 10.1038/srep24776 -
Genome Biology and Evolution Apr 2017Over the past decade, there has been a rising interest in Achromobacter sp., an emerging opportunistic pathogen responsible for nosocomial and cystic fibrosis lung...
Over the past decade, there has been a rising interest in Achromobacter sp., an emerging opportunistic pathogen responsible for nosocomial and cystic fibrosis lung infections. Species of this genus are ubiquitous in the environment, can outcompete resident microbiota, and are resistant to commonly used disinfectants as well as antibiotics. Nevertheless, the Achromobacter genus suffers from difficulties in diagnosis, unresolved taxonomy and limited understanding of how it adapts to the cystic fibrosis lung, not to mention other host environments. The goals of this first genus-wide comparative genomics study were to clarify the taxonomy of this genus and identify genomic features associated with pathogenicity and host adaptation. This was done with a widely applicable approach based on pan-genome analysis. First, using all publicly available genomes, a combination of phylogenetic analysis based on 1,780 conserved genes with average nucleotide identity and accessory genome composition allowed the identification of a largely clinical lineage composed of Achromobacter xylosoxidans, Achromobacter insuavis, Achromobacter dolens, and Achromobacter ruhlandii. Within this lineage, we identified 35 positively selected genes involved in metabolism, regulation and efflux-mediated antibiotic resistance. Second, resistome analysis showed that this clinical lineage carried additional antibiotic resistance genes compared with other isolates. Finally, we identified putative mobile elements that contribute 53% of the genus's resistome and support horizontal gene transfer between Achromobacter and other ecologically similar genera. This study provides strong phylogenetic and pan-genomic bases to motivate further research on Achromobacter, and contributes to the understanding of opportunistic pathogen evolution.
PubMed: 28383665
DOI: 10.1093/gbe/evx061 -
MSystems Jun 2021Bacterial pathogens evolve during chronic colonization of the human host by selection for pathoadaptive mutations. One of the emerging and understudied bacterial species...
Bacterial pathogens evolve during chronic colonization of the human host by selection for pathoadaptive mutations. One of the emerging and understudied bacterial species causing chronic airway infections in patients with cystic fibrosis (CF) is Achromobacter xylosoxidans. It can establish chronic infections in patients with CF, but the genetic and phenotypic changes associated with adaptation during these infections are not completely understood. In this study, we analyzed the whole-genome sequences of 55 clinical A. xylosoxidans isolates longitudinally collected from the sputum of 6 patients with CF. Four genes encoding regulatory proteins and two intergenic regions showed convergent evolution, likely driven by positive selection for pathoadaptive mutations, across the different clones of A. xylosoxidans. Most of the evolved isolates had lower swimming motility and were resistant to multiple classes of antibiotics, while fewer of the evolved isolates had slower growth or higher biofilm production than the first isolates. Using a genome-wide association study method, we identified several putative genetic determinants of biofilm formation, motility and β-lactam resistance in this pathogen. With respect to antibiotic resistance, we discovered that a combination of mutations in pathoadaptive genes ( and ) and two other genes encoding regulatory proteins ( and ) were associated with increased resistance to meropenem and ceftazidime. Altogether, our results suggest that genetic changes within regulatory loci facilitate within-host adaptation of A. xylosoxidans and the emergence of adaptive phenotypes, such as antibiotic resistance or biofilm formation. A thorough understanding of bacterial pathogen adaptation is essential for the treatment of chronic bacterial infections. One unique challenge in the analysis and interpretation of genomics data is identifying the functional impact of mutations accumulated in the bacterial genome during colonization in the human host. Here, we investigated the genomic and phenotypic evolution of A. xylosoxidans in chronic airway infections of patients with CF and identified several mutations associated with the phenotypic evolution of this pathogen using genome-wide associations. Identification of phenotypes under positive selection and the associated mutations can enlighten the adaptive processes of this emerging pathogen in human infections and pave the way for novel therapeutic interventions.
PubMed: 34184916
DOI: 10.1128/mSystems.00523-21 -
Marine Drugs Jan 2022sp. GET02.ST and sp. GET02.AC were isolated together from the gut of the wharf roach, , inhabiting the intertidal zone of the west coast of Korea. The... (Comparative Study)
Comparative Study
sp. GET02.ST and sp. GET02.AC were isolated together from the gut of the wharf roach, , inhabiting the intertidal zone of the west coast of Korea. The co-cultivation of these two strains significantly induced the production of two new metabolites, ligiamycins A () and B (), which were barely detected in the single culture of sp. GET02.ST. The planar structures of ligiamycins A () and B () were elucidated as new decalins coupled with amino-maleimides by the analysis of various spectroscopic data, including nuclear magnetic resonance (NMR), ultraviolet (UV), and mass (MS) data. The assignment of two nitrogen atoms in amino-maleimide in was accomplished based on H-N heteroatom single quantum coherence spectroscopy (HSQC) NMR experiments. The relative configurations of the ligiamycins were determined using rotating frame Overhauser effect spectroscopy (ROESY) NMR data, and their absolute configurations were deduced by comparing their experimental and calculated optical rotations. Ligiamycin A () displayed antibacterial effects against and , while ligiamycin B () exhibited mild cell cytotoxicity against human colorectal cancer cells.
Topics: Animals; Humans; Achromobacter; Anti-Bacterial Agents; Antineoplastic Agents; Cell Line, Tumor; Coculture Techniques; Colorectal Neoplasms; Isopoda; Naphthalenes; Streptomyces; Maleimides
PubMed: 35200613
DOI: 10.3390/md20020083 -
Infection and Immunity Dec 2023Cystic fibrosis (CF) is a genetic disease affecting epithelial ion transport, resulting in thickened mucus and impaired mucociliary clearance. Persons with CF (pwCF)...
Cystic fibrosis (CF) is a genetic disease affecting epithelial ion transport, resulting in thickened mucus and impaired mucociliary clearance. Persons with CF (pwCF) experience life-long infections of the respiratory mucosa caused by a diverse array of opportunists, which are leading causes of morbidity and mortality. In recent years, there has been increased appreciation for the range and diversity of microbes causing CF-related respiratory infections. The introduction of new therapeutics and improved detection methodology has revealed CF-related opportunists such as (). is a Gram-negative bacterial species which is widely distributed in environmental sources and has been increasingly observed in sputa and other samples from pwCF, typically in patients in later stages of CF disease. In this study, we characterized CF clinical isolates of and tested colonization and persistence of in respiratory infection using immortalized human CF respiratory epithelial cells and BALB/c mice. Genomic analyses of clinical isolates showed homologs for factors including flagellar synthesis, antibiotic resistance, and toxin secretion systems. isolates adhered to polarized cultures of CFBE41o- human immortalized CF bronchial epithelial cells and caused significant cytotoxicity and depolarization of cell layers. colonized and persisted in mouse lungs for up to 72 h post infection, with inflammatory consequences that include increased neutrophil influx in the lung, lung damage, cytokine production, and mortality. We also identified genes that are differentially expressed in synthetic CF sputum media. Based on these results, we conclude that is an opportunistic pathogen of significance in CF.
Topics: Animals; Mice; Humans; Achromobacter denitrificans; Cystic Fibrosis; Sputum; Gram-Negative Bacterial Infections; Respiratory Tract Infections; Gene Expression Profiling
PubMed: 37909751
DOI: 10.1128/iai.00416-23 -
Journal of Clinical Microbiology Jul 2017species are increasingly being detected in cystic fibrosis (CF) patients, with an unclear epidemiology and impact. We studied a cohort of patients attending a Canadian...
species are increasingly being detected in cystic fibrosis (CF) patients, with an unclear epidemiology and impact. We studied a cohort of patients attending a Canadian adult CF clinic who had positive sputum cultures for species in the period from 1984 to 2013. Infection was categorized as transient or persistent (≥50% positive cultures for 1 year). Those with persistent infection were matched 2:1 with age-, sex-, and time-matched controls without a history of infection, and mixed-effects models were used to assess pulmonary exacerbation (PEx) frequency and lung function decline. Isolates from a biobank were retrospectively assessed, identified to the species level by sequencing, and genotyped using pulsed-field gel electrophoresis (PFGE). Thirty-four patients (11% of those in our clinic), with a median age of 24 years (interquartile range [IQR], 20.3 to 29.8 years), developed infection. Ten patients (29%) developed persistent infection. Persistence did not denote permanence, as most patients ultimately cleared infection, often after years. Patients were more likely to experience PEx at incident isolation than at prior or subsequent visits (odds ratio [OR], 2.7 [95% confidence interval {CI}, 1.2 to 6.7]; = 0.03). Following persistent infection, there was no difference in annual lung function decline (-1.08% [95% CI, -2.73 to 0.57%] versus -2.74% [95% CI, -4.02 to 1.46%]; = 0.12) or the odds of PEx (OR, 1.21 [95% CI, 0.45 to 3.28]; = 0.70). Differential virulence among species was not observed, and no cases of transmission occurred. We demonstrated that incident infection was associated with a greater risk of PEx; however, neither transient nor chronic infection was associated with a worsened long-term prognosis. Large, multicenter studies are needed to clarify the clinical impact, natural history, and transmissibility of .
Topics: Achromobacter; Adolescent; Adult; Cystic Fibrosis; Female; Follow-Up Studies; Gram-Negative Bacterial Infections; Humans; Male; North America; Prevalence; Respiratory Function Tests; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 28446570
DOI: 10.1128/JCM.02556-16 -
Microbiology Spectrum Aug 2022Achromobacter xylosoxidans is an opportunistic pathogen implicated in a wide variety of human infections including the ability to colonize the lungs of cystic fibrosis...
Achromobacter xylosoxidans is an opportunistic pathogen implicated in a wide variety of human infections including the ability to colonize the lungs of cystic fibrosis (CF) patients. The role of A. xylosoxidans in human pathology remains controversial due to the lack of optimized and model systems to identify and test bacterial gene products that promote a pathological response. We have previously identified macrophages as a target host cell for A. xylosoxidans-induced cytotoxicity. By optimizing our macrophage infection model, we determined that A. xylosoxidans enters macrophages and can reside within a membrane bound vacuole for extended periods of time. Intracellular replication appears limited with cellular lysis preceding an enhanced, mainly extracellular replication cycle. Using our optimized model system along with transposon mutagenesis, we identified 163 genes that contribute to macrophage cytotoxicity. From this list, we characterized a giant RTX adhesin encoded downstream of a type one secretion system (T1SS) that mediates bacterial binding and entry into host macrophages, an important first step toward cellular toxicity and inflammation. The RTX adhesin is encoded by other human isolates and is recognized by antibodies present in serum isolated from CF patients colonized by A. xylosoxidans, indicating this virulence factor is produced and deployed . This study represents the first characterization of A. xylosoxidans replication during infection and identifies a variety of genes that may be linked to virulence and human pathology. Patients affected by CF develop chronic bacterial infections characterized by inflammatory exacerbations and tissue damage. Advancements in sequencing technologies have broadened the list of opportunistic pathogens colonizing the CF lung. A. xylosoxidans is increasingly recognized as an opportunistic pathogen in CF, yet our understanding of the bacterium as a contributor to human disease is limited. Genomic studies have identified potential virulence determinants in A. xylosoxidans isolates, but few have been mechanistically studied. Using our optimized cell model, we identified and characterized a bacterial adhesin that mediates binding and uptake by host macrophages leading to cytotoxicity. A subset of serum samples from CF patients contains antibodies that recognize the RTX adhesion, suggesting, for the first time, that this virulence determinant is produced . This work furthers our understanding of A. xylosoxidans virulence factors at a mechanistic level.
Topics: Achromobacter denitrificans; Adhesins, Bacterial; Cystic Fibrosis; Gram-Negative Bacterial Infections; Humans; Macrophages; Virulence; Virulence Factors
PubMed: 35856670
DOI: 10.1128/spectrum.02083-22 -
Frontiers in Cellular and Infection... 2022Bacteria of the genus are environmental germs, with an unknown reservoir. It can become opportunistic pathogens in immunocompromised patients, causing bacteremia,...
Bacteria of the genus are environmental germs, with an unknown reservoir. It can become opportunistic pathogens in immunocompromised patients, causing bacteremia, meningitis, pneumonia, or peritonitis. In recent years, has emerged with increasing incidence in patients with cystic fibrosis (CF). Recent studies showed that is involved in the degradation of the respiratory function of patients with CF. The respiratory ecosystem of patients with CF is colonized by bacterial species that constantly fight for space and access to nutrients. The type VI secretion system (T6SS) empowers this constant bacterial antagonism, and it is used as a virulence factor in several pathogenic bacteria. This study aimed to investigate the prevalence of the T6SS genes in isolated in patients with CF. We also evaluated clinical and molecular characteristics of T6SS-positive strains. We showed that possesses a T6SS gene cluster and that some environmental and clinical isolates assemble a functional T6SS nanomachine T6SS is used to target competing bacteria, including other CF-specific pathogens. Finally, we demonstrated the importance of the T6SS in the internalization of in lung epithelial cells and that the T6SS protein Hcp is detected in the sputum of patients with CF. Altogether, these results suggest for the first time a role of T6SS in CF-lung colonization by and opens promising perspective to target this virulence determinant as innovative theranostic options for CF management.
Topics: Achromobacter denitrificans; Cystic Fibrosis; Ecosystem; Gram-Negative Bacterial Infections; Humans; Lung; Type VI Secretion Systems; Virulence Factors
PubMed: 35782124
DOI: 10.3389/fcimb.2022.859181