scholarly journals Mobilome Analysis of Achromobacter spp. Isolates from Chronic and Occasional Lung Infection in Cystic Fibrosis Patients

2021 ◽  
Vol 9 (1) ◽  
pp. 130
Author(s):  
Laura Veschetti ◽  
Angela Sandri ◽  
Cristina Patuzzo ◽  
Paola Melotti ◽  
Giovanni Malerba ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Opportunistic Pathogen ◽  
Lung Infection ◽  
Achromobacter Xylosoxidans ◽  
Type Ii ◽  
Genome Sequences ◽  
Integrative And Conjugative Elements ◽  
Pathogenic Genes ◽  
Antimicrobial Resistance Genes ◽  
Lung Infections

Achromobacter spp. is an opportunistic pathogen that can cause lung infections in patients with cystic fibrosis (CF). Although a variety of mobile genetic elements (MGEs) carrying antimicrobial resistance genes have been identified in clinical isolates, little is known about the contribution of Achromobacter spp. mobilome to its pathogenicity. To provide new insights, we performed bioinformatic analyses of 54 whole genome sequences and investigated the presence of phages, insertion sequences (ISs), and integrative and conjugative elements (ICEs). Most of the detected phages were previously described in other pathogens and carried type II toxin-antitoxin systems as well as other pathogenic genes. Interestingly, the partial sequence of phage Bcep176 was found in all the analyzed Achromobacter xylosoxidans genome sequences, suggesting the integration of this phage in an ancestor strain. A wide variety of IS was also identified either inside of or in proximity to pathogenicity islands. Finally, ICEs carrying pathogenic genes were found to be widespread among our isolates and seemed to be involved in transfer events within the CF lung. These results highlight the contribution of MGEs to the pathogenicity of Achromobacter species, their potential to become antimicrobial targets, and the need for further studies to better elucidate their clinical impact.

Consensus “Cystic Fibrosis: definition, diagnostic criteria, treatment” Section “Microbiology and Epidemiology of chronic respiratory infections in cystic fibrosis”

2016 ◽  
Vol 7 (1) ◽  
pp. 80-96
Author(s):  
Igor A Shaginyan ◽  
Marina Yu Chernukha ◽  
Nikolay I Kapranov ◽  
Elena I Kondratyeva ◽  
Nataliya Yu Kashirskaya ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Respiratory Infections ◽  
Lung Infection ◽  
Achromobacter Xylosoxidans ◽  
Wide Range ◽  
Causative Agents ◽  
Small Colony ◽  
Lung Infections ◽  
Atypical Phenotype

The main causative agents of lung infection in patients with cystic fibrosis (CF) are P. aeruginosa, S. aureus and H. influenzae. In the last decade, gram-negative nonfermentative microorganisms (NFMO) - Вurkholderia cepacia complex (Bcc), Stenotrophomonas maltophilia, Achromobacter xylosoxidans and non-tuberculous mycobacteria, fungi of the genus Aspergillus have acquired the clinical significance. It is found that the chronic lung infection in 2/3 of the cases caused by association of microorganisms. Among hospitalized patients, in contrast to outpatients, these associations are represented by two, three or more species of microorganisms. The associations of P. aeruginosa + S. aureus (18,2 %) and P. aeruginosa + Bcc (9,1 %) are the most common. Other representatives - A. xylosoxidans, S. maltophilia and A. baumanii - is often identified in the associations of microorganisms. The focuses of chronic lung infections are formed in patients with increasing age. The dominant pathogens are P. aeruginosa and S. aureus. The methicillinresistant staphylococci and P. aeruginosa strains with a mucoid phenotype are of particular importance for cystic fibrosis patients. Bcc isolates from cystic fibrosis patients in Russia often belong to genomovar III A-B. cenocepacia. The Bcc strains colonize the lower airways of patients with CF and are able for long-term persistence and transmission from patient to patient. The resistance to many antibiotics is the main feature of the P. aeruginosa, S. aureus and Bcc strains. The strains of microorganisms with atypical phenotype (small colony variants) are formed under the action of the antibiotic. Infections caused by Bcc and other NFMO are difficult to identify and we need to use a wide range of bacteriological, biochemical, molecular biological techniques and mass spectrometry.

scholarly journals Heterogenous response to R-pyocin killing in populations of Pseudomonas aeruginosa sourced from cystic fibrosis lungs

2020 ◽  
Author(s):  
Madeline Mei ◽  
Jacob Thomas ◽  
Stephen P. Diggle
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Genotypic Diversity ◽  
Opportunistic Pathogen ◽  
Chronic Infections ◽  
Bacterial Populations ◽  
Heterogeneous Populations ◽  
Lung Infections ◽  
The Impact ◽  
Lps Binding

AbstractBacteriocins are proteinaceous antimicrobials produced by bacteria which are active against other strains of the same species. R-type pyocins are phage tail-like bacteriocins produced by Pseudomonas aeruginosa. Due to their anti-pseudomonal activity, R-pyocins have potential as therapeutics in infection. P. aeruginosa is a Gram-negative opportunistic pathogen and is particularly problematic for individuals with cystic fibrosis (CF). P. aeruginosa from CF lung infections develop increasing resistance to antibiotics, making new treatment approaches essential. P. aeruginosa populations become phenotypically and genotypically diverse during infection, however little is known of the efficacy of R-pyocins against heterogeneous populations. R-pyocins vary by subtype (R1-R5), distinguished by binding to different residues on the lipopolysaccharide (LPS). Each type varies in killing spectrum, and each strain produces only one R-type. To evaluate the prevalence of different R-types, we screened P. aeruginosa strains from the International Pseudomonas Consortium Database (IPCD) and from our biobank of CF strains. We found that (i) R1-types were the most prevalent R-type among strains from respiratory sources and (ii) isolates collected from the same patient have the same R-type. We then assessed the impact of diversity on R-pyocin susceptibility and found a heterogenous response to R-pyocins within populations, likely due to differences in the LPS core. Our work reveals that heterogeneous populations of microbes exhibit variable susceptibility to R-pyocins and highlights that there is likely heterogeneity in response to other types of LPS-binding antimicrobials, including phage.ImportanceR-pyocins have potential as alternative therapeutics against Pseudomonas aeruginosa in chronic infection, however little is known about the efficacy of R-pyocins in heterogeneous bacterial populations. P. aeruginosa is known to become resistant to multiple antibiotics, as well as evolve phenotypic and genotypic diversity over time; thus it is particularly difficult to eradicate in chronic cystic fibrosis (CF) lung infections. In this study, we found that P. aeruginosa populations from CF lungs maintain the same R-pyocin genotype but exhibit heterogeneity in susceptibility to R-pyocins from other strains. Our findings suggest there is likely heterogeneity in response to other types of LPS-binding antimicrobials, such as phage, highlighting the necessity of further studying the potential of LPS-binding antimicrobial particles as alternative therapies in chronic infections.

scholarly journals Membrane-Bound Nitrate Reductase Is Required for Anaerobic Growth in Cystic Fibrosis Sputum

2007 ◽  
Vol 189 (12) ◽  
pp. 4449-4455 ◽  
Author(s):  
Kelli L. Palmer ◽  
Stacie A. Brown ◽  
Marvin Whiteley
Keyword(s):  
Cystic Fibrosis ◽  
Nitrate Reductase ◽  
Mutational Analysis ◽  
Autosomal Recessive Disorder ◽  
Opportunistic Pathogen ◽  
Anaerobic Growth ◽  
Expression Of Genes ◽  
Membrane Bound ◽  
Lung Infections

ABSTRACT The autosomal recessive disorder cystic fibrosis (CF) affects approximately 70,000 people worldwide and is characterized by chronic bacterial lung infections with the opportunistic pathogen Pseudomonas aeruginosa. To form a chronic CF lung infection, P. aeruginosa must grow and proliferate within the CF lung, and the highly viscous sputum within the CF lung provides a likely growth substrate. Recent evidence indicates that anaerobic microenvironments may be present in the CF lung sputum layer. Since anaerobic growth significantly enhances P. aeruginosa biofilm formation and antibiotic resistance, it is important to examine P. aeruginosa physiology and metabolism in anaerobic environments. Measurement of nitrate levels revealed that CF sputum contains sufficient nitrate to support significant P. aeruginosa growth anaerobically, and mutational analysis revealed that the membrane-bound nitrate reductase is essential for P. aeruginosa anaerobic growth in an in vitro CF sputum medium. In addition, expression of genes coding for the membrane-bound nitrate reductase complex is responsive to CF sputum nitrate levels. These findings suggest that the membrane-bound nitrate reductase is critical for P. aeruginosa anaerobic growth with nitrate in the CF lung.

Phage therapy against Achromobacter xylosoxidans lung infection in a patient with cystic fibrosis: a case report

2018 ◽  
Vol 169 (9) ◽  
pp. 540-542 ◽  
Author(s):  
N. Hoyle ◽  
P. Zhvaniya ◽  
N. Balarjishvili ◽  
D. Bolkvadze ◽  
L. Nadareishvili ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Case Report ◽  
Phage Therapy ◽  
Lung Infection ◽  
Achromobacter Xylosoxidans

scholarly journals Hypermutation as an Evolutionary Mechanism for Achromobacter xylosoxidans in Cystic Fibrosis Lung Infection

Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 72 ◽  
Author(s):  
Laura Veschetti ◽  
Angela Sandri ◽  
Helle Krogh Johansen ◽  
Maria M. Lleò ◽  
Giovanni Malerba
Keyword(s):  
Cystic Fibrosis ◽  
De Novo ◽  
Large Deletion ◽  
Achromobacter Xylosoxidans ◽  
Chronic Infections ◽  
Dna Mismatch ◽  
Integrative And Conjugative Elements ◽  
Adaptive Mechanisms ◽  
Host Evolution ◽  
Protease Secretion

Achromobacter xylosoxidans can cause chronic infections in the lungs of patients with cystic fibrosis (CF) by adapting to the specific environment. The study of longitudinal isolates allows to investigate its within-host evolution to unravel the adaptive mechanisms contributing to successful colonization. In this study, four clinical isolates longitudinally collected from two chronically infected patients underwent whole genome sequencing, de novo assembly and sequence analysis. Phenotypic assays were also performed. The isolates coming from one of the patients (patient A) presented a greater number of genetic variants, diverse integrative and conjugative elements, and different protease secretion. In the first of these isolates (strain A1), we also found a large deletion in the mutS gene, involved in DNA mismatch repair (MMR). In contrast, isolates from patient B showed a lower number of variants, only one integrative and mobilizable element, no phenotypic changes, and no mutations in the MMR system. These results suggest that in the two patients the establishment of a chronic infection was mediated by different adaptive mechanisms. While the strains isolated from patient B showed a longitudinal microevolution, strain A1 can be clearly classified as a hypermutator, confirming the occurrence and importance of this adaptive mechanism in A. xylosoxidans infection.

scholarly journals Scnn1b-Transgenic BALB/c Mice as a Model of Pseudomonas aeruginosa Infections of the Cystic Fibrosis Lung

2020 ◽  
Vol 88 (9) ◽  
Author(s):  
Kristen J. Brao ◽  
Brendan P. Wille ◽  
Joshua Lieberman ◽  
Robert K. Ernst ◽  
Mark E. Shirtliff ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Immune Cell ◽  
Opportunistic Pathogen ◽  
Sodium Absorption ◽  
Lung Pathology ◽  
Wild Type ◽  
Content Type ◽  
Lung Infections ◽  
Content Modeling

ABSTRACT The opportunistic pathogen Pseudomonas aeruginosa is responsible for much of the morbidity and mortality associated with cystic fibrosis (CF), a condition that predisposes patients to chronic lung infections. P. aeruginosa lung infections are difficult to treat because P. aeruginosa adapts to the CF lung, can develop multidrug resistance, and can form biofilms. Despite the clinical significance of P. aeruginosa, modeling P. aeruginosa infections in CF has been challenging. Here, we characterize Scnn1b-transgenic (Tg) BALB/c mice as P. aeruginosa lung infection models. Scnn1b-Tg mice overexpress the epithelial Na+ channel (ENaC) in their lungs, driving increased sodium absorption that causes lung pathology similar to CF. We intranasally infected Scnn1b-Tg mice and wild-type littermates with the laboratory P. aeruginosa strain PAO1 and CF clinical isolates and then assessed differences in bacterial clearance, cytokine responses, and histological features up to 12 days postinfection. Scnn1b-Tg mice carried higher bacterial burdens when infected with biofilm-grown rather than planktonic PAO1; Scnn1b-Tg mice also cleared infections more slowly than their wild-type littermates. Infection with PAO1 elicited significant increases in proinflammatory and Th17-linked cytokines on day 3. Scnn1b-Tg mice infected with nonmucoid early CF isolates maintained bacterial burdens and mounted immune responses similar to those of PAO1-infected Scnn1b-Tg mice. In contrast, Scnn1b-Tg mice infected with a mucoid CF isolate carried high bacterial burdens, produced significantly more interleukin 1β (IL-1β), IL-13, IL-17, IL-22, and KC, and showed severe immune cell infiltration into the bronchioles. Taken together, these results show the promise of Scnn1b-Tg mice as models of early P. aeruginosa colonization in the CF lung.

scholarly journals Frequency of quorum sensing mutations in Pseudomonas aeruginosa strains isolated from different environments

2021 ◽  
Author(s):  
Kathleen O’Connor ◽  
Conan Y. Zhao ◽  
Stephen P. Diggle
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Opportunistic Pathogen ◽  
Human Infection ◽  
Multiple Infection ◽  
Loss Of Function ◽  
Mutational Signatures ◽  
Amino Acid Length ◽  
Lung Infections

AbstractPseudomonas aeruginosa uses quorum sensing (QS) to coordinate the expression of multiple genes necessary for establishing and maintaining infection. lasR QS mutations have been shown to frequently arise in cystic fibrosis (CF) lung infections, however, there has been far less emphasis on determining whether QS system mutations arise across other environments. To test this, we utilized 852 publicly available sequenced P. aeruginosa genomes from the Pseudomonas International Consortium Database (IPCD) to study P. aeruginosa QS mutational signatures. We found that across all isolates, LasR is the most variable protein sequence compared to other QS proteins. In order to study isolates by source, we focused on a subset of 654 isolates collected from CF, wounds, and non-infection environmental isolates, where we could clearly identify their source. Using this sub-set analysis, we found that LasR mutations are not specific to CF lungs, but are common across all environments. We then used amino acid length as a proxy for observing loss of function in LasR proteins among the strains. We found that truncated LasR proteins are more abundant in P. aeruginosa strains isolated from human infection than the environment. Overall, our findings suggest that the evolution of lasR QS mutations in P. aeruginosa are common and not limited to infection environments.ImportancePseudomonas aeruginosa is an opportunistic pathogen which is often isolated from infection and environmental sources. P. aeruginosa uses quorum sensing (QS) to establish and adapt to infection environments. QS in P. aeruginosa is controlled by a complex hierarchical gene network in which the transcriptional regulator LasR has traditionally been thought to play a major controlling role. Despite this, lasR mutants are frequently isolated from chronic infection sites including the cystic fibrosis lung. Using an online P. aeruginosa strain database, we determined the frequency of mutation in key QS genes in multiple infection and non-infection environments and found that mutations and truncations in the lasR gene is more common than in other QS genes. Further, we found that lasR mutants are common in both infection and environmental strains. These findings further our understanding of QS in P. aeruginosa and have implications for the development of future therapies designed to inhibit QS.

scholarly journals Draft Genome Sequence for Pseudomonas aeruginosa Strain PAO579, a Mucoid Derivative of PAO381

2012 ◽  
Vol 194 (23) ◽  
pp. 6617-6617 ◽  
Author(s):  
T. Ryan Withers ◽  
Shannon L. Johnson ◽  
Hongwei D. Yu
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Genome Sequence ◽  
Draft Genome ◽  
Opportunistic Pathogen ◽  
Lung Infection ◽  
Draft Genome Sequence ◽  
Content Type ◽  
Chronic Lung Infection

ABSTRACTPseudomonas aeruginosais an opportunistic pathogen that establishes a chronic lung infection in individuals afflicted with cystic fibrosis. Here, we announce the draft genome ofP. aeruginosastrain PAO579, an alginate-overproducing derivative of strain PAO381.

scholarly journals Is the Potable Water System an Advantageous Preinfection Niche for Bacteria Colonizing the Cystic Fibrosis Lung?

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Matthew J. Wargo
Keyword(s):  
Cystic Fibrosis ◽  
Burkholderia Cepacia ◽  
Stenotrophomonas Maltophilia ◽  
Potable Water ◽  
Water System ◽  
Achromobacter Xylosoxidans ◽  
Low Oxygen ◽  
Content Type ◽  
Lung Infections ◽  
Successful Colonization

ABSTRACTPeople with cystic fibrosis are susceptible to lung infections from a variety of bacteria, a number of which also reside in the potable water system, includingPseudomonas aeruginosa,Stenotrophomonas maltophilia,Achromobacter xylosoxidans,Burkholderia cepaciacomplex, and nontuberculosisMycobacteria. Here, I propose chemical and physical aspects of the potable water system along with bacterial lifestyle strategies in this system that may enhance successful colonization of cystic fibrosis lungs by these bacteria, including iron and copper levels, lipids, and low growth rates within low-oxygen biofilms.

scholarly journals A Case of Phage Therapy against Pandrug-Resistant Achromobacter xylosoxidans in a 12-Year-Old Lung-Transplanted Cystic Fibrosis Patient

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 60
Author(s):  
David Lebeaux ◽  
Maia Merabishvili ◽  
Eric Caudron ◽  
Damien Lannoy ◽  
Leen Van Simaey ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Cystic Fibrosis Patient ◽  
Phage Therapy ◽  
Lung Infection ◽  
Achromobacter Xylosoxidans ◽  
Resistant Bacteria ◽  
Low Grade ◽  
First Case ◽  
Phage Receptor ◽  
Airway Colonization

Bacteriophages are a promising therapeutic strategy among cystic fibrosis and lung-transplanted patients, considering the high frequency of colonization/infection caused by pandrug-resistant bacteria. However, little clinical data are available regarding the use of phages for infections with Achromobacter xylosoxidans. A 12-year-old lung-transplanted cystic fibrosis patient received two rounds of phage therapy because of persistent lung infection with pandrug-resistant A. xylosoxidans. Clinical tolerance was perfect, but initial bronchoalveolar lavage (BAL) still grew A. xylosoxidans. The patient’s respiratory condition slowly improved and oxygen therapy was stopped. Low-grade airway colonization by A. xylosoxidans persisted for months before samples turned negative. No re-colonisation occurred more than two years after phage therapy was performed and imipenem treatment was stopped. Whole genome sequencing indicated that the eight A. xylosoxidans isolates, collected during phage therapy, belonged to four delineated strains, whereby one had a stop mutation in a gene for a phage receptor. The dynamics of lung colonisation were documented by means of strain-specific qPCRs on different BALs. We report the first case of phage therapy for A. xylosoxidans lung infection in a lung-transplanted patient. The dynamics of airway colonization was more complex than deduced from bacterial culture, involving phage susceptible as well as phage resistant strains.

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