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Frontiers in Bioscience (Landmark... Dec 2021In recent years, advances in diagnosis and treatment have significantly modified the short- and long-term prognosis of cystic fibrosis (CF) patients. However, as in the... (Review)
Review
In recent years, advances in diagnosis and treatment have significantly modified the short- and long-term prognosis of cystic fibrosis (CF) patients. However, as in the past, the most important health problem that has significantly reduced the quality of life in CF patients is the progressive deterioration of lung structure and function. In recent years, Achromobacter species have emerged with increasing incidence in the respiratory secretions of CF subjects. The significance of this detection remains debated. In this review article, the characteristics of these pathogens, the importance of their presence in CF patients, and possible antibiotic treatment of treatments for colonization and infection are discussed. Literature analysis shows that Achromobacter species, mainly A. xylosoxidans, are pathogens with intrinsic characteristics that favour persistent lung colonization and several virulence factors and secretion systems that significantly interfere with respiratory cell survival. However, although it seems undebatable that Achromobacterspecies detection is a marker of CF severity, the role of these pathogens as a cause of lung structure and functional deterioration is not definitively established. Nonetheless, there is general agreement about the need for antibiotic therapy to eradicate these pathogens when they are detected in CF patients. Unfortunately, eradication is difficult, and no standard treatment is recommended by scientific societies. New possibilities are potentially offered by some recently developed drugs, such as cefiderocol, but further studies on the dosage, treatment duration and efficacy and safety of this new antibiotic in CF patients of different ages are urgently needed.
Topics: Achromobacter; Anti-Bacterial Agents; Cystic Fibrosis; Gram-Negative Bacterial Infections; Humans; Lung; Quality of Life
PubMed: 34994175
DOI: 10.52586/5054 -
Journal of Clinical Microbiology Mar 2021species are increasingly being detected in patients with cystic fibrosis (CF), and this emerging pathogen is associated with antibiotic resistance and more-severe...
species are increasingly being detected in patients with cystic fibrosis (CF), and this emerging pathogen is associated with antibiotic resistance and more-severe disease outcomes. Nonetheless, little is known about the extent of transmission and antibiotic resistance development in infections. We sequenced the genomes of 101 clinical isolates (identified as based on matrix-assister laser desorption ionization-time of flight [MALDI-TOF] or API N20 typing) collected from 51 patients with CF-the largest longitudinal data set to date. We performed phylogenetic analysis on the genomes and combined this with epidemiological and antibiotic resistance data to identify patient-to-patient transmission and the development of antibiotic resistance. We confirmed that the MALDI-TOF or API N20 method was not sufficient for species-level typing and that the population of isolates was composed of five different species, among which accounted for 52% of infections. Most patients were infected by unique clone types; nonetheless, suspected patient-to-patient transmission cases identified by shared clone types were observed in 35% ( = 18) of patients. In 15 of 16 cases, the suspected transmissions were further supported by genome- or clinic visit-based epidemiological analysis. Finally, we found that resistance developed over time. We show that whole-genome sequencing (WGS) is essential for species typing and identification of patient-to-patient transmission, which was revealed for , , and, for the first time, Furthermore, we show that the development of antibiotic resistance is associated with chronic infections. Our findings emphasize that transmission and antibiotic resistance should be considered in future treatment strategies.
Topics: Achromobacter; Cystic Fibrosis; Drug Resistance, Microbial; Gram-Negative Bacterial Infections; Humans; Phylogeny
PubMed: 33472899
DOI: 10.1128/JCM.02911-20 -
Applied and Environmental Microbiology Nov 2021In this study, comprehensive analyses were performed to determine the function of an atypical MarR homolog in sp. strain As-55. Genomic analyses of sp. As-55 showed...
In this study, comprehensive analyses were performed to determine the function of an atypical MarR homolog in sp. strain As-55. Genomic analyses of sp. As-55 showed that this is located adjacent to an gene. ArsV is a flavin-dependent monooxygenase that confers resistance to the antibiotic methylarsenite [MAs(III)], the organoarsenic compound roxarsone(III) [Rox(III)], and the inorganic antimonite [Sb(III)]. Similar genes are widely distributed in arsenic-resistant bacteria. Phylogenetic analyses showed that these MarRs are found in operons predicted to be involved in resistance to inorganic and organic arsenic species, so the subfamily was named MarR. MarR orthologs have three conserved cysteine residues, which are Cys36, Cys37, and Cys157 in sp. As-55, mutation of which compromises the response to MAs(III)/Sb(III). GFP-fluorescent biosensor assays show that AdMarR (MarR protein of Achromobacter deleyi As-55) responds to trivalent As(III) and Sb(III) but not to pentavalent As(V) or Sb(V). The results of RT-qPCR assays show that is expressed constitutively in a deletion mutant, indicating that represses transcription of . Moreover, electrophoretic mobility shift assays (EMSAs) demonstrate that AdMarR binds to the promoters of both and in the absence of ligands and that DNA binding is relieved upon binding of As(III) and Sb(III). Our results demonstrate that AdMarR is a novel As(III)/Sb(III)-responsive transcriptional repressor that controls expression of which confers resistance to MAs(III), Rox(III), and Sb(III). AdMarR and its orthologs form a subfamily of MarR proteins that regulate genes conferring resistance to arsenic-containing antibiotics. In this study, a MarR family member, AdMarR was shown to regulate the gene, which confers resistance to arsenic-containing antibiotics. It is a founding member of a distinct subfamily that we refer to as MarR, regulating genes conferring resistance to arsenic and antimony antibiotic compounds. AdMarR was shown to be a repressor containing conserved cysteine residues that are required to bind As(III) and Sb(III), leading to a conformational change and subsequent derepression. Here we show that members of the MarR family are involved in regulating arsenic-containing compounds.
Topics: Achromobacter; Anti-Bacterial Agents; Arsenic; Arsenicals; Cysteine; Drug Resistance, Bacterial; Genes, Bacterial; Multigene Family; Phylogeny; Roxarsone
PubMed: 34613763
DOI: 10.1128/AEM.01588-21 -
Microorganisms Jul 2022Case reports and small series indicate that species bloodstream infection (BSI) is most commonly a complication of hospitalization among patients with chronic lung...
BACKGROUND
Case reports and small series indicate that species bloodstream infection (BSI) is most commonly a complication of hospitalization among patients with chronic lung disease. The aim of the present study was to determine the incidence, risk factors, and outcomes of sp. BSI in an Australian population.
METHODS
Retrospective, laboratory-based surveillance was conducted in Queensland, Australia (population ≈ 5 million) during 2000-2019. Clinical and outcome data were obtained by linkage to state hospital admissions and vital statistics databases. BSI diagnosed within the community or within the first two calendar days of stay in hospital were classified as community-onset. Community-onset BSIs were grouped into community-associated and healthcare-associated.
RESULTS
During more than 86 million person-years of surveillance, 210 incidents of sp. BSI occurred among 195 individuals for an overall age-and sex-standardized annual incidence of 2.6 per million residents. Older individuals and males were at highest risk (2.9 vs. 2.0 per million, IRR for males 1.5; 95% CI, 1.1-1.9; = 0.008). Most (153; 73%) cases were of community-onset of which 100 (48%) and 53 (25%) were healthcare- and community-associated, respectively. An increasing proportion of community-onset cases were observed during twenty years of surveillance. Underlying medical illnesses were common with median (interquartile range) Charlson Comorbidity Index (CCI) scores of 3 (1-5). CCI scores of 0, 1, 2, and 3+ were observed in 37 (18%), 27 (13%), 40 (19%), and 105 (50%) of cases, respectively. All but one of the cases were admitted to hospital for a median (interquartile range) length of stay of 12 (5-34) days. All-cause case-fatality rates in hospital by day 30 and by day 90 were 30 (14%), 28 (13%), and 42 (20%), respectively. The 90-day case-fatality rate increased with increasing comorbidity and was 3% (1/37), 11% (3/27), 25% (10/40), and 27% (28/105) among those with Charlson Comorbidity Indices of 0, 1, 2, and 3+, respectively ( = 0.004).
CONCLUSIONS
Although comorbidity is an important determinant of risk, most sp. BSI are of community-onset and one-fifth of cases occur in patients without significant underlying chronic co-morbidities. This study highlights the value of population-based methodologies to define the epidemiology of an infectious disease.
PubMed: 35889168
DOI: 10.3390/microorganisms10071449 -
Cell Reports Aug 2023How the opportunistic Gram-negative pathogens of the genus Achromobacter interact with the innate immune system is poorly understood. Using three Achromobacter clinical...
How the opportunistic Gram-negative pathogens of the genus Achromobacter interact with the innate immune system is poorly understood. Using three Achromobacter clinical isolates from two species, we show that the type 3 secretion system (T3SS) is required to induce cell death in human macrophages by inflammasome-dependent pyroptosis. Macrophages deficient in the inflammasome sensors NLRC4 or NLRP3 undergo pyroptosis upon bacterial internalization, but those deficient in both NLRC4 and NLRP3 do not, suggesting either sensor mediates pyroptosis in a T3SS-dependent manner. Detailed analysis of the intracellular trafficking of one isolate indicates that the intracellular bacteria reside in a late phagolysosome. Using an intranasal mouse infection model, we observe that Achromobacter damages lung structure and causes severe illness, contingent on a functional T3SS. Together, we demonstrate that Achromobacter species can survive phagocytosis by promoting macrophage cell death and inflammation by redundant mechanisms of pyroptosis induction in a T3SS-dependent manner.
Topics: Humans; Animals; Mice; Pyroptosis; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Type III Secretion Systems; Achromobacter; Disease Models, Animal; Calcium-Binding Proteins; CARD Signaling Adaptor Proteins
PubMed: 37598340
DOI: 10.1016/j.celrep.2023.113012 -
Journal of Natural Products Nov 2023Through genome mining efforts, two lasso peptide biosynthetic gene clusters (BGCs) within two different species of , a genus that contains pathogenic organisms that can...
Through genome mining efforts, two lasso peptide biosynthetic gene clusters (BGCs) within two different species of , a genus that contains pathogenic organisms that can infect patients with cystic fibrosis, were discovered. Using gene-refactored BGCs in , these lasso peptides, which were named achromonodin-1 and achromonodin-2, were heterologously expressed. Achromonodin-1 is naturally encoded by certain isolates from the sputum of patients with cystic fibrosis. The NMR structure of achromonodin-1 was determined, demonstrating that it is a threaded lasso peptide with a large loop and short tail structure, reminiscent of previously characterized lasso peptides that inhibit RNA polymerase (RNAP). Achromonodin-1 inhibits RNAP and has potent, focused activity toward , another isolate from the sputum of a cystic fibrosis patient. These efforts expand the repertoire of antimicrobial lasso peptides and provide insights into how isolates from certain ecological niches interact with each other.
Topics: Humans; Escherichia coli; Cystic Fibrosis; Peptides; Antimicrobial Peptides; Achromobacter; DNA-Directed RNA Polymerases
PubMed: 37870195
DOI: 10.1021/acs.jnatprod.3c00536 -
Seminars in Respiratory and Critical... Apr 2023Progressive obstructive lung disease secondary to chronic airway infection, coupled with impaired host immunity, is the leading cause of morbidity and mortality in... (Review)
Review
Progressive obstructive lung disease secondary to chronic airway infection, coupled with impaired host immunity, is the leading cause of morbidity and mortality in cystic fibrosis (CF). Classical pathogens found in the airways of persons with CF (pwCF) include the complex, species, and While traditional respiratory-tract surveillance culturing has focused on this limited range of pathogens, the use of both comprehensive culture and culture-independent molecular approaches have demonstrated complex highly personalized microbial communities. Loss of bacterial community diversity and richness, counteracted with relative increases in dominant taxa by traditional CF pathogens such as or , have long been considered the hallmark of disease progression. Acquisition of these classic pathogens is viewed as a harbinger of advanced disease and postulated to be driven in part by recurrent and frequent antibiotic exposure driven by frequent acute pulmonary exacerbations. Recently, CF transmembrane conductance regulator (CFTR) modulators, small molecules designed to potentiate or restore diminished protein levels/function, have been successfully developed and have profoundly influenced disease course. Despite the multitude of clinical benefits, structural lung damage and consequent chronic airway infection persist in pwCF. In this article, we review the microbial epidemiology of pwCF, focus on our evolving understanding of these infections in the era of modulators, and identify future challenges in infection surveillance and clinical management.
Topics: Humans; Cystic Fibrosis; Lung; Disease Progression; Burkholderia cepacia complex; Microbiota; Pseudomonas aeruginosa
PubMed: 36623820
DOI: 10.1055/s-0042-1758732 -
Microorganisms May 2023The respiratory tract of lung transplant recipients (LTR) is likely to be colonized with non-fermentative Gram-negative rods. As a consequence of the improvements in... (Review)
Review
The respiratory tract of lung transplant recipients (LTR) is likely to be colonized with non-fermentative Gram-negative rods. As a consequence of the improvements in molecular sequencing and taxonomy, an increasing number of bacterial species have been described. We performed a review of the literature of bacterial infections in LTR involving non-fermentative Gram-negative rods with exclusion of , , spp. and spp. Overall, non-fermenting GNR were recovered from 17 LTR involving the following genera: , , , , , and . We then discuss the issues raised by these bacteria, including detection and identification, antimicrobial resistance, pathogenesis, and cross-transmission.
PubMed: 37374970
DOI: 10.3390/microorganisms11061468 -
Microorganisms Jan 2023This work provides the basis for implementing a continuous treatment system using a bacterial consortium for wastewater containing a pesticide mixture of iprodione (IPR)...
This work provides the basis for implementing a continuous treatment system using a bacterial consortium for wastewater containing a pesticide mixture of iprodione (IPR) and chlorpyrifos (CHL). Two bacterial strains ( C1 and C4) isolated from the biomixture of a biopurification system were able to efficiently remove pesticides IPR and CHL at different concentrations (10 to 100 mg L) from the liquid medium as individual strains and free consortium. The half-life time () for IPR and CHL was determined for individual strains and a free bacterial consortium. However, when the free bacterial consortium was used, a lower was obtained, especially for CHL. Based on these results, an immobilized bacterial consortium was formulated with each bacterial strain encapsulated individually in alginate beads. Then, different inoculum concentrations (5, 10, and 15% ) of the immobilized consortium were evaluated in batch experiments for IPR and CHL removal. The inoculum concentration of 15% demonstrated the highest pesticide removal. Using this inoculum concentration, the packed-bed bioreactor with an immobilized bacterial consortium was operated in continuous mode at different flow rates (30, 60, and 90 mL h) at a pesticide concentration of 50 mg L each. The performance in the bioreactor demonstrated that it is possible to efficiently remove a pesticide mixture of IPR and CHL in a continuous system. The metabolites 3,5-dichloroaniline (3,5-DCA) and 3,5,6-trichloro-2-pyridinol (TCP) were produced, and a slight accumulation of TCP was observed. The bioreactor was influenced by TCP accumulation but was able to recover performance quickly. Finally, after 60 days of operation, the removal efficiency was 96% for IPR and 82% for CHL. The findings of this study demonstrate that it is possible to remove IPR and CHL from pesticide-containing wastewater in a continuous system.
PubMed: 36677512
DOI: 10.3390/microorganisms11010220 -
Microbiology Spectrum Apr 2022Achromobacter denitrificans is an environmental opportunistic pathogen that is infecting a large number of immunocompromised patients. A more recently identified strain...
Achromobacter denitrificans is an environmental opportunistic pathogen that is infecting a large number of immunocompromised patients. A more recently identified strain from the historical collection of strains of Achromobacter denitrificans is Achromobacter mucicolens. In hosts with a variety of underlying diseases, spp. can induce a wide spectrum of disorders. Because of the bacterium's intrinsic genetic constitution and resistance gained over time, antibiotics are challenged to handle Due to the fact that is rare and its taxonomy is not completely understood, it is difficult to define clinical symptoms, acquisition risk factors, and thus the best therapeutic course of action. To help comprehend this intrinsic and acquired resistance, we analyzed the entire genome of the strain and utilized bioinformatics methods to estimate the strain's probable drug resistance profile. In our study, we have isolated and cultured a clinically important strain and subjected it to antimicrobial susceptibility tests against antibiotics in the Vitek 2 testing system. The strain's genome sequence as well as an investigation of 27 of its phenotypic traits provides important information regarding this pathogen. The genome of this strain possesses a number of antibiotic resistance genes that code for efflux pump systems and other antibiotic-regulating as well as -modifying enzymes. Our research analysis predicted genes involved in drug resistance, including genes for efflux pump systems, antibiotic efflux, antibiotic inactivation, and antibiotic target alteration. studies validated the genomic evidence for its ability to exhibit resistance against a wide range of antibiotics. Our investigation paves the way for more research on understanding the functioning of the key discovered genes that contribute toward the pathogenicity of and hence gives new information and treatment options for this emerging pathogen. species are well-known opportunistic human pathogens that can be found in water and soil and most commonly in hospital settings. They thrive in immunocompromised individuals, producing sporadic cases of pneumonia, septicemia, peritonitis, urinary tract infections, and other illnesses. strains are inherently resistant to a wide spectrum of antibiotics, making them difficult to treat promptly. The strain under study, , was notably resistant to various antibiotics, and the infection could be controlled only after several rounds of prescription medications at different doses. This consumed a lot of time and put the already immunosuppressed leukemic patient through a great ordeal. The study aimed to raise awareness about the importance of the bacterium's lethality, and doctors should evaluate the bacterium's potential for resistance before prescribing antibiotics. Sanitation and other precautions should also be implemented in hospitals and other public places.
Topics: Achromobacter; Achromobacter denitrificans; Anti-Bacterial Agents; Drug Resistance, Microbial; Genomics; Humans; Microbial Sensitivity Tests
PubMed: 35377213
DOI: 10.1128/spectrum.01916-21