scholarly journals Genomic and Phenotypic Evolution of Achromobacter xylosoxidans during Chronic Airway Infections of Patients with Cystic Fibrosis

mSystems ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
S. M. Hossein Khademi ◽  
Migle Gabrielaite ◽  
Magnus Paulsson ◽  
Mattis Knulst ◽  
Eleni Touriki ◽  
...  

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 function impact of mutations accumulated in the bacterial genome during colonization in the human host.

2020 ◽  
Vol 6 (4) ◽  
pp. 381
Author(s):  
Sabine Renner ◽  
Edith Nachbaur ◽  
Peter Jaksch ◽  
Eleonora Dehlink

Cystic fibrosis is the most common autosomal-recessive metabolic disease in the Western world. Impaired trans-membrane chloride transport via the cystic fibrosis transmembrane conductance regulator (CFTR) protein causes thickened body fluids. In the respiratory system, this leads to chronic suppurative cough and recurrent pulmonary infective exacerbations, resulting in progressive lung damage and respiratory failure. Whilst the impact of bacterial infections on CF lung disease has long been recognized, our understanding of pulmonary mycosis is less clear. The range and detection rates of fungal taxa isolated from CF airway samples are expanding, however, in the absence of consensus criteria and univocal treatment protocols for most respiratory fungal conditions, interpretation of laboratory reports and the decision to treat remain challenging. In this review, we give an overview on fungal airway infections in CF and CF-lung transplant recipients and focus on the most common fungal taxa detected in CF, Aspergillus fumigatus, Candida spp., Scedosporium apiospermum complex, Lomentospora species, and Exophiala dermatitidis, their clinical presentations, common treatments and prophylactic strategies, and clinical challenges from a physician’s point of view.


Nanoscale ◽  
2021 ◽  
Author(s):  
Wei He ◽  
Zaiyu Wang ◽  
Haotian Bai ◽  
Zheng Zhao ◽  
Ryan T. K. Kwok ◽  
...  

Biofilm-related infections such as dental plaque, chronic sinusitis, native valve endocarditis, and chronic airway infections in cystic fibrosis have brought serious suffering to patients and financial burdens to society. Materials...


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dariusz Jarych ◽  
Ewa Augustynowicz-Kopec ◽  
Agnieszka Iwanska ◽  
Pawel Parniewski ◽  
Marta Majchrzak

AbstractPseudomonas aeruginosa is a severe bacterial pathogen. Due to the genetic flexibility among strains, chronic airways infection can lead to mortality among cystic fibrosis (CF) patients. It is essential to develop patient-specific therapy which will rely on phenotypic and genomic diversity. The primary objective of this study was to assess the genomic variability of P. aeruginosa strains, using two different molecular techniques for tracking the epidemiological transmissions. This study applied a multiple-locus variable-number tandem-repeat (VNTR) analysis (MLVA) for an efficient genotyping of clinical P. aeruginosa strains isolated from CF patients and compared results with a TRS-PCR typing. The percentage similarity analysis was performed using the categorical multi-state coefficient and UPGMA method. Based on the MLVA and TRS-PCR group assessment, 43 P. aeruginosa strains/variants were detected among the 63 clinical isolates from eight CF patients. The study of P. aeruginosa isolates has revealed that during chronic bacterial infections, CF patients harbor different P. aeruginosa strains or variants within the same host over the years. P. aeruginosa genotypes diversity may result from infection with several strains and result from a microevolution process of an initially acquired strain. The TRS-PCR method proposed in this work can complement the MLVA scheme. It can also be used as a preliminary method for genetic typing of P. aeruginosa isolates in CF patients.


1999 ◽  
Vol 37 (4) ◽  
pp. 291-293 ◽  
Author(s):  
B. Cimon ◽  
J. Carrere ◽  
J. P. Chazalette ◽  
J. F. Vinatier ◽  
D. Chabasse ◽  
...  

Pneumologie ◽  
2016 ◽  
Vol 70 (10) ◽  
Author(s):  
G Suarez-Cuartin ◽  
O Sibila ◽  
A Smith ◽  
H Abo-Leyah ◽  
A Rodrigo-Troyano ◽  
...  

Author(s):  
Erin Felton ◽  
Aszia Burrell ◽  
Hollis Chaney ◽  
Iman Sami ◽  
Anastassios C. Koumbourlis ◽  
...  

Abstract Background Cystic fibrosis (CF) affects >70,000 people worldwide, yet the microbiologic trigger for pulmonary exacerbations (PExs) remains unknown. The objective of this study was to identify changes in bacterial metabolic pathways associated with clinical status. Methods Respiratory samples were collected at hospital admission for PEx, end of intravenous (IV) antibiotic treatment, and follow-up from 27 hospitalized children with CF. Bacterial DNA was extracted and shotgun DNA sequencing was performed. MetaPhlAn2 and HUMAnN2 were used to evaluate bacterial taxonomic and pathway relative abundance, while DESeq2 was used to evaluate differential abundance based on clinical status. Results The mean age of study participants was 10 years; 85% received combination IV antibiotic therapy (beta-lactam plus a second agent). Long-chain fatty acid (LCFA) biosynthesis pathways were upregulated in follow-up samples compared to end of treatment: gondoate (p = 0.012), oleate (p = 0.048), palmitoleate (p = 0.043), and pathways of fatty acid elongation (p = 0.012). Achromobacter xylosoxidans and Escherichia sp. were also more prevalent in follow-up compared to PEx (p < 0.001). Conclusions LCFAs may be associated with persistent infection of opportunistic pathogens. Future studies should more closely investigate the role of LCFA production by lung bacteria in the transition from baseline wellness to PEx in persons with CF. Impact Increased levels of LCFAs are found after IV antibiotic treatment in persons with CF. LCFAs have previously been associated with increased lung inflammation in asthma. This is the first report of LCFAs in the airway of persons with CF. This research provides support that bacterial production of LCFAs may be a contributor to inflammation in persons with CF. Future studies should evaluate LCFAs as predictors of future PExs.


2021 ◽  
Vol 9 (4) ◽  
pp. 762
Author(s):  
Lucia Henrici De Angelis ◽  
Noemi Poerio ◽  
Vincenzo Di Pilato ◽  
Federica De Santis ◽  
Alberto Antonelli ◽  
...  

Phage therapy is now reconsidered with interest in the treatment of bacterial infections. A major piece of information for this application is the definition of the molecular targets exploited by phages to infect bacteria. Here, the genetic basis of resistance to the lytic phage φBO1E by its susceptible host Klebsiella pneumoniae KKBO-1 has been investigated. KKBO-1 phage-resistant mutants were obtained by infection at high multiplicity. One mutant, designated BO-FR-1, was selected for subsequent experiments, including virulence assessment in a Galleria mellonella infection model and characterization by whole-genome sequencing. Infection with BO-FR-1 was associated with a significantly lower mortality when compared to that of the parental strain. The BO-FR-1 genome differed from KKBO-1 by a single nonsense mutation into the wbaP gene, which encodes a glycosyltransferase involved in the first step of the biosynthesis of the capsular polysaccharide (CPS). Phage susceptibility was restored when BO-FR-1 was complemented with the constitutive wbaP gene. Our results demonstrated that φBO1E infects KKBO-1 targeting the bacterial CPS. Interestingly, BO-FR-1 was less virulent than the parental strain, suggesting that in the context of the interplay among phage, bacterial pathogen and host, the emergence of phage resistance may be beneficial for the host.


Author(s):  
Daniel J Wolter ◽  
Alison Scott ◽  
Catherine R Armbruster ◽  
Dale Whittington ◽  
John S Edgar ◽  
...  

Abstract Background Bacteria adapt to survive and grow in different environments. Genetic mutations that promote bacterial survival under harsh conditions can also restrict growth. The causes and consequences of these adaptations have important implications for diagnosis, pathogenesis, and therapy. Objectives We describe the isolation and characterization of an antibiotic-dependent, temperature-sensitive Pseudomonas aeruginosa mutant chronically infecting the respiratory tract of a cystic fibrosis (CF) patient, underscoring the clinical challenges bacterial adaptations can present. Methods Respiratory samples collected from a CF patient during routine care were cultured for standard pathogens. P. aeruginosa isolates recovered from samples were analysed for in vitro growth characteristics, antibiotic susceptibility, clonality, and membrane phospholipid and lipid A composition. Genetic mutations were identified by whole genome sequencing. Results P. aeruginosa isolates collected over 5 years from respiratory samples of a CF patient frequently harboured a mutation in phosphatidylserine decarboxylase (psd), encoding an enzyme responsible for phospholipid synthesis. This mutant could only grow at 37°C when in the presence of supplemented magnesium, glycerol, or, surprisingly, the antibiotic sulfamethoxazole, which the source patient had repeatedly received. Of concern, this mutant was not detectable on standard selective medium at 37°C. This growth defect correlated with alterations in membrane phospholipid and lipid A content. Conclusions A P. aeruginosa mutant chronically infecting a CF patient exhibited dependence on sulphonamides and would likely evade detection using standard clinical laboratory methods. The diagnostic and therapeutic challenges presented by this mutant highlight the complex interplay between bacterial adaptation, antibiotics, and laboratory practices, during chronic bacterial infections.


mBio ◽  
2014 ◽  
Vol 5 (3) ◽  
Author(s):  
Rasmus Lykke Marvig ◽  
Søren Damkiær ◽  
S. M. Hossein Khademi ◽  
Trine M. Markussen ◽  
Søren Molin ◽  
...  

ABSTRACTPseudomonas aeruginosaairway infections are a major cause of mortality and morbidity of cystic fibrosis (CF) patients. In order to persist,P. aeruginosadepends on acquiring iron from its host, and multiple different iron acquisition systems may be active during infection. This includes the pyoverdine siderophore and thePseudomonasheme utilization (phu) system. While the regulation and mechanisms of several iron-scavenging systems are well described, it is not clear whether such systems are targets for selection during adaptation ofP. aeruginosato the host environment. Here we investigated the within-host evolution of the transmissibleP. aeruginosaDK2 lineage. We found positive selection for promoter mutations leading to increased expression of thephusystem. By mimicking conditions of the CF airwaysin vitro, we experimentally demonstrate that increased expression ofphuRconfers a growth advantage in the presence of hemoglobin, thus suggesting thatP. aeruginosaevolves toward iron acquisition from hemoglobin. To rule out that this adaptive trait is specific to the DK2 lineage, we inspected the genomes of additionalP. aeruginosalineages isolated from CF airways and found similar adaptive evolution in two distinct lineages (DK1 and PA clone C). Furthermore, in all three lineages,phuRpromoter mutations coincided with the loss of pyoverdine production, suggesting that within-host adaptation toward heme utilization is triggered by the loss of pyoverdine production. Targeting heme utilization might therefore be a promising strategy for the treatment ofP. aeruginosainfections in CF patients.IMPORTANCEMost bacterial pathogens depend on scavenging iron within their hosts, which makes the battle for iron between pathogens and hosts a hallmark of infection. Accordingly, the ability of the opportunistic pathogenPseudomonas aeruginosato cause chronic infections in cystic fibrosis (CF) patients also depends on iron-scavenging systems. While the regulation and mechanisms of several such iron-scavenging systems have been well described, not much is known about how the within-host selection pressures act on the pathogens’ ability to acquire iron. Here, we investigated the within-host evolution ofP. aeruginosa, and we found evidence thatP. aeruginosaduring long-term infections evolves toward iron acquisition from hemoglobin. This adaptive strategy might be due to a selective loss of other iron-scavenging mechanisms and/or an increase in the availability of hemoglobin at the site of infection. This information is relevant to the design of novel CF therapeutics and the development of models of chronic CF infections.


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