scholarly journals Burkholderia cepacia infection in a non-cystic fibrosis patient: an arcane presentation

2021 ◽  
Vol 3 (4) ◽  
Author(s):  
Sufyan Ibrahim ◽  
Haritha Madigubba ◽  
Himanshu Y. N ◽  
Kiran Chawla
Keyword(s):  
Cystic Fibrosis ◽  
Burkholderia Cepacia ◽  
Type Species ◽  
Pulmonary Function Tests ◽  
Response To Therapy ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Content Type ◽  
Link Type ◽  
Exacerbation Of Copd

Introduction. Burkholderia cepacia is an aerobic, Gram-negative bacillus, which exhibits innate resistance to multiple antibiotics and disinfectants. Although it is a chronic colonizer of the respiratory tract, it may rarely present with fatal necrotizing pneumonia-like features in immunosuppressed individuals, as those with chronic granulomatous disease, or patients with significant pulmonary compromise, like cystic fibrosis. Case Presentation. A 76-year-old male presented with complaints of breathlessness, cough with mucoid expectoration and fever for 3 days. He had a history of coronary artery disease, chronic obstructive pulmonary disease (COPD), diabetes mellitus and hypertension, under treatment. Pulmonary function tests were suggestive of very severe obstruction (FEV1/FVC was 55 %). So, clinical diagnosis of acute exacerbation of COPD was established. Sputum culture grew B. cepacia . The patient was treated with ceftazidime and meropenem along with inhalational bronchodilators and steroids, and showed symptomatic response to therapy. Conclusion. There is paucity of the literature describing B. cepacia as a potential cause for acute exacerbations in relatively common clinical conditions, such as COPD. This case report highlights the speculation of this rare possibility, thereby alerting a clinician dealing with such cases.

scholarly journals Stenotrophomonas maltophilia phenotypic and genotypic features through 4-year cystic fibrosis lung colonization

2020 ◽  
Author(s):  
Eliana Alcaraz ◽  
Daniela Centrón ◽  
Gabriela Camicia ◽  
María Paula Quiroga ◽  
José Di Conza ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Adult Patient ◽  
Virulence Factors ◽  
Stenotrophomonas Maltophilia ◽  
Type Species ◽  
Mutation Frequency ◽  
Content Type ◽  
Link Type ◽  
Clonal Relatedness ◽  
Over Time

Introduction. Stenotrophomonas maltophilia has emerged as one of the most common multi-drug-resistant pathogens isolated from people with cystic fibrosis (CF). However, its adaptation over time to CF lungs has not been fully established. Hypothesis. Sequential isolates of S. maltophilia from a Brazilian adult patient are clonally related and show a pattern of adaptation by loss of virulence factors. Aim. To investigate antimicrobial susceptibility, clonal relatedness, mutation frequency, quorum sensing (QS) and selected virulence factors in sequential S. maltophilia isolates from a Brazilian adult patient attending a CF referral centre in Buenos Aires, Argentina, between May 2014 and May 2018. Methodology. The antibiotic resistance of 11 S. maltophilia isolates recovered from expectorations of an adult female with CF was determined. Clonal relatedness, mutation frequency, QS variants (RpfC–RpfF), QS autoinducer (DSF) and virulence factors were investigated in eight viable isolates. Results. Seven S. maltophilia isolates were resistant to trimethoprim–sulfamethoxazole and five to levofloxacin. All isolates were susceptible to minocycline. Strong, weak and normomutators were detected, with a tendency to decreased mutation rate over time. XbaI PFGE revealed that seven isolates belong to two related clones. All isolates were RpfC–RpfF1 variants and DSF producers. Only two isolates produced weak biofilms, but none displayed swimming or twitching motility. Four isolates showed proteolytic activity and amplified stmPr1 and stmPr2 genes. Only the first three isolates were siderophore producers. Four isolates showed high resistance to oxidative stress, while the last four showed moderate resistance. Conclusion. The present study shows the long-time persistence of two related S. maltophilia clones in an adult female with CF. During the adaptation of the prevalent clones to the CF lungs over time, we identified a gradual loss of virulence factors that could be associated with the high amounts of DSF produced by the evolved isolates. Further, a decreased mutation rate was observed in the late isolates. The role of all these adaptations over time remains to be elucidated from a clinical perspective, probably focusing on the damage they can cause to CF lungs.

Environment in the lung of cystic fibrosis patients stimulates the expression of biofilm phenotype in Mycobacterium abscessus

2022 ◽  
Vol 71 (1) ◽  
Author(s):  
Bailey F. Keefe ◽  
Luiz E. Bermudez
Keyword(s):  
Cystic Fibrosis ◽  
Host Cell ◽  
Biofilm Formation ◽  
Type Species ◽  
Divalent Cations ◽  
Mycobacterium Abscessus ◽  
Content Type ◽  
Link Type ◽  
Populations At Risk

Introduction. Pulmonary infections caused by organisms of the Mycobacterium abscessus complex are increasingly prevalent in populations at risk, such as patients with cystic fibrosis, bronchiectasis and emphysema. Hypothesis. M. abscessus infection of the lung is not observed in immunocompetent individuals, which raises the possibility that the compromised lung environment is a suitable niche for the pathogen to thrive in due to the overproduction of mucus and high amounts of host cell lysis. Aim. Evaluate the ability of M. abscessus to form biofilm and grow utilizing in vitro conditions as seen in immunocompromised lungs of patients. Methodology. We compared biofilm formation and protein composition in the presence and absence of synthetic cystic fibrosis medium (SCFM) and evaluated the bacterial growth when exposed to human DNA. Results. M. abscessus is capable of forming biofilm in SCFM. By eliminating single components found in the medium, it became clear that magnesium works as a signal for the biofilm formation, and chelation of the divalent cations resulted in the suppression of biofilm formation. Investigation of the specific proteins expressed in the presence of SCFM and in the presence of SCFM lacking magnesium revealed many different proteins between the conditions. M. abscessus also exhibited growth in SCFM and in the presence of host cell DNA, although the mechanism of DNA utilization remains unclear. Conclusions. In vitro conditions mimicking the airways of patients with cystic fibrosis appear to facilitate M. abscessus establishment of infection, and elimination of magnesium from the environment may affect the ability of the pathogen to establish infection.

scholarly journals Pseudoxanthomonas winnipegensis sp. nov., derived from human clinical materials and recovered from cystic fibrosis and other patient types in Canada, and emendation of Pseudoxanthomonas spadix Young et al. 2007

2020 ◽  
Vol 70 (12) ◽  
pp. 6313-6322
Author(s):  
Kathryn A. Bernard ◽  
Alicia Vachon ◽  
Ana Luisa Pacheco ◽  
Tamara Burdz ◽  
Deborah Wiebe ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Cystic Fibrosis ◽  
Type Species ◽  
Gene Sequencing ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Whole Genome ◽  
Content Type ◽  
Link Type ◽  
Rrna Gene Sequencing

Twelve isolates recovered from 10 cystic fibrosis/other patient types and a variety of clinical sources, were referred to Canada's National Microbiology Laboratory over 7 years. These were assignable to the genus Pseudoxanthomonas but were unidentifiable to species level. Patients included five males and five females from two geographically separated provinces, ranging in age from 2 months to 84 years. In contrast, most Pseudoxanthomonas species described to date have been derived from water, plants or contaminated soils. By 16S rRNA gene sequencing, the patient strains had ≥99.4 % similarity to each other but only 97.73–98.29 % to their closest relatives, Pseudoxanthomonas spadix or Pseudoxanthomonas helianthi . Bacteria were studied by whole genome sequencing using average nucleotide identity by Blastn, digital DNA–DNA hybridization, average amino acid identity, core genome and single nucleotide variant analyses, MALDI-TOF, biochemical and cellular fatty acid analyses, and by antimicrobial susceptibility testing. Bacterial structures were assessed using scanning and transmission electron microscopy. Strains were strict aerobes, yellowish-pigmented, oxidative, non-motile, Gram-stain-negative bacilli and generally unable to reduce nitrate. Strains were susceptible to most of the antibiotics tested; some resistance was observed towards carbapenems, several cephems and uniformly to nitrofurantoin. The single taxon group observed by 16S rRNA gene sequencing was supported by whole genome sequencing; genomes ranged in size from 4.36 to 4.73 Mb and had an average G+C content of 69.12 mol%. Based on this study we propose the name Pseudoxanthomonas winnipegensis sp. nov. for this cluster. Pseudoxanthomonas spadix DSM 18855T, acquired for this study, was found to be non-motile phenotypically and by electron microscopy; we therefore propose the emendation of Pseudoxanthomonas spadix Young et al. 2007 to document that observation.

2-Alkyl-4-quinolone quorum sensing molecules are biomarkers for culture-independent Pseudomonas aeruginosa burden in adults with cystic fibrosis

2021 ◽  
Vol 70 (10) ◽  
Author(s):  
Nur Masirah M. Zain ◽  
Karmel Webb ◽  
Iain Stewart ◽  
Nigel Halliday ◽  
David A. Barrett ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Type Species ◽  
Bacterial Load ◽  
Pulmonary Exacerbation ◽  
Content Type ◽  
Link Type ◽  
Culture Independent ◽  
Clinical Stability

Introduction. Pseudomonas aeruginosa produces quorum sensing signalling molecules including 2-alkyl-4-quinolones (AQs), which regulate virulence factor production in the cystic fibrosis (CF) airways. Hypothesis/Gap statement. Culture can lead to condition-dependent artefacts which may limit the potential insights and applications of AQs as minimally-invasive biomarkers of bacterial load. Aim. We aimed to use culture-independent methods to explore the correlations between AQ levels and live P. aeruginosa load in adults with CF. Methodology. Seventy-five sputum samples at clinical stability and 48 paired sputum samples obtained at the beginning and end of IV antibiotics for a pulmonary exacerbation in adults with CF were processed using a viable cell separation technique followed by quantitative P. aeruginosa polymerase chain reaction (qPCR). Live P. aeruginosa qPCR load was compared with the concentrations of three AQs (HHQ, NHQ and HQNO) detected in sputum, plasma and urine. Results. At clinical stability and the beginning of IV antibiotics for pulmonary exacerbation, HHQ, NHQ and HQNO measured in sputum, plasma and urine were consistently positively correlated with live P. aeruginosa qPCR load in sputum, compared to culture. Following systemic antibiotics live P. aeruginosa qPCR load decreased significantly (P<0.001) and was correlated with a reduction in plasma NHQ (plasma: r=0.463, P=0.003). Conclusion. In adults with CF, AQ concentrations correlated more strongly with live P. aeruginosa bacterial load measured by qPCR compared to traditional culture. Prospective studies are required to assess the potential of systemic AQs as biomarkers of P. aeruginosa bacterial burden.

scholarly journals Mycobacterium mucogenicum meningitis due to external ventricular drain

2020 ◽  
Vol 2 (11) ◽  
Author(s):  
Salwa Moiz ◽  
Omar Rahman ◽  
Mark Morcos ◽  
Asma Siddiqui ◽  
Usman Bin Hameed
Keyword(s):  
Type Species ◽  
Obstructive Hydrocephalus ◽  
External Ventricular Drain ◽  
Response To Therapy ◽  
Case Presentation ◽  
Content Type ◽  
Link Type ◽  
First Case ◽  
Neurological Exam ◽  
Mycobacterium Mucogenicum

Introduction. Mycobacterium mucogenicum is a rare non-tuberculous organism associated with catheter-related infections when pathogenic in humans. We present the first case of an external ventricular drain (EVD)-associated M. mucogenicum meningitis. Case presentation. A 55-year-old woman had EVD placement for obstructive hydrocephalus following traumatic subarachnoid haemorrhage. Cerebrospinal fluid (CSF) was obtained 5 days later for fever and neurological changes. M. mucogenicum was ultimately isolated from the CSF and the patient was placed on appropriate antibiotics. Her management included replacement of the EVD and a prolonged course of anti-mycobacterial antibiotics. CSF findings showed her response to therapy and neurological exam improved after 6 weeks. Conclusion. M. mucogenicum infections are very rare and existing reports indicate that it may be a device- or catheter-related pathogen. This microorganism has not been previously associated with an EVD. Ours may be the first documented report of EVD-related M. mucogenicum infection.

scholarly journals Matrix-assisted laser desorption/ionization time-of-flight MS for the accurate identification of Burkholderia cepacia complex and Burkholderia gladioli in the clinical microbiology laboratory

2020 ◽  
Vol 69 (8) ◽  
pp. 1105-1113
Author(s):  
Kendrew S. K. Wong ◽  
Suk Dhaliwal ◽  
Jennifer Bilawka ◽  
Jocelyn A. Srigley ◽  
Sylvie Champagne ◽  
...  
Keyword(s):  
Burkholderia Cepacia ◽  
Type Species ◽  
Laser Desorption ◽  
Species Level ◽  
Laser Desorption Ionization ◽  
Ionization Time ◽  
Content Type ◽  
Link Type ◽  
Maldi Tof ◽  
Burkholderia Gladioli

Introduction. Burkholderia cepacia complex (Bcc) bacteria, currently consisting of 23 closely related species, and Burkholderia gladioli , can cause serious and difficult-to-treat infections in people with cystic fibrosis. Identifying Burkholderia bacteria to the species level is considered important for understanding epidemiology and infection control, and predicting clinical outcomes. Matrix-assisted laser desorption/ionization time-of-flight MS (MALDI-TOF) is a rapid method recently introduced in clinical laboratories for bacterial species-level identification. However, reports on the ability of MALDI-TOF to accurately identify Bcc to the species level are mixed. Aim. The aim of this project was to evaluate the accuracy of MALDI-TOF using the Biotyper and VITEK MS systems in identifying isolates from 22 different Bcc species and B. gladioli compared to recA gene sequencing, which is considered the current gold standard for Bcc. Methodology. To capture maximum intra-species variation, phylogenetic trees were constructed from concatenated multi-locus sequence typing alleles and clustered with a novel k-medoids approach. One hundred isolates representing 22 Bcc species, plus B. gladioli , were assessed for bacterial identifications using the two MALDI-TOF systems. Results. At the genus level, 100 and 97.0 % of isolates were confidently identified as Burkholderia by the Biotyper and VITEK MS systems, respectively; moreover, 26.0 and 67.0 % of the isolates were correctly identified to the species level, respectively. In many, but not all, cases of species misidentification or failed identification, a representative library for that species was lacking. Conclusion. Currently available MALDI-TOF systems frequently do not accurately identify Bcc bacteria to the species level.

scholarly journals Comparative genomics of ST5 and ST30 methicillin-resistant Staphylococcus aureus sequential isolates recovered from paediatric patients with cystic fibrosis

2021 ◽  
Vol 7 (3) ◽  
Author(s):  
María Sol Haim ◽  
Rahat Zaheer ◽  
Amrita Bharat ◽  
Sabrina Di Gregorio ◽  
José Di Conza ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Type Species ◽  
Methicillin Resistant ◽  
Content Type ◽  
Airway Infection ◽  
Synonymous Mutations ◽  
Link Type ◽  
Mrsa Strains

Staphylococcus aureus chronic airway infection in patients with cystic fibrosis (CF) allows this pathogen to adapt over time in response to different selection pressures. We have previously shown that the main sequence types related to community-acquired methicillin-resistant S. aureus (MRSA) infections in Argentina – ST5 and ST30 – are also frequently isolated from the sputum of patients with CF, but in these patients they usually display multi-drug antimicrobial resistance. In this study, we sequenced the genomes of MRSA from four paediatric CF patients with the goal of identifying mutations among sequential isolates, especially those possibly related to antimicrobial resistance and virulence, which might contribute to the adaptation of the pathogen in the airways of patients with CF. Our results revealed genetic differences in sequential MRSA strains isolated from patients with CF in both their core and accessory genomes. Although the genetic adaptation of S. aureus was distinct in different hosts, we detected independent mutations in thyA, htrA, rpsJ and gyrA – which are known to have crucial roles in S. aureus virulence and antimicrobial resistance – in isolates recovered from multiple patients. Moreover, we identified allelic variants that were detected in all of the isolates recovered after a certain time point; these non-synonymous mutations were in genes associated with antimicrobial resistance, virulence, iron scavenging and oxidative stress resistance. In conclusion, our results provide evidence of genetic variability among sequential MRSA isolates that could be implicated in the adaptation of these strains during chronic CF airway infection.

scholarly journals Genomics reveals the novel species placement of industrial contaminant isolates incorrectly identified as Burkholderia lata

2021 ◽  
Vol 7 (4) ◽  
Author(s):  
Edward Cunningham-Oakes ◽  
Tom Pointon ◽  
Barry Murphy ◽  
Stuart Campbell-Lee ◽  
Gordon Webster ◽  
...  
Keyword(s):  
Burkholderia Cepacia ◽  
Type Species ◽  
Manufacturing Industry ◽  
Core Gene ◽  
Resistant Bacteria ◽  
Accurate Identification ◽  
Content Type ◽  
Link Type ◽  
Industrial Contaminants ◽  
Industrial Strains

The Burkholderia cepacia complex (Bcc) is a closely related group of bacteria, composed of at least 20 different species, the accurate identification of which is essential in the context of infectious diseases. In industry, they can contaminate non-food products, including home and personal care products and cosmetics. The Bcc are problematic contaminants due to their ubiquitous presence and intrinsic antimicrobial resistance, which enables them to occasionally overcome preservation systems in non-sterile products. Burkholderia lata and Burkholderia contaminans are amongst the Bcc bacteria encountered most frequently as industrial contaminants, but their identification is not straightforward. Both species were historically established as a part of a group known collectively as taxon K, based upon analysis of the recA gene and multilocus sequence typing (MLST). Here, we deploy a straightforward genomics-based workflow for accurate Bcc classification using average nucleotide identity (ANI) and core-gene analysis. The workflow was used to examine a panel of 23 Burkholderia taxon K industrial strains, which, based on MLST, comprised 13 B. lata, 4 B. contaminans and 6 unclassified Bcc strains. Our genomic identification showed that the B. contaminans strains retained their classification, whilst the remaining strains were reclassified as Burkholderia aenigmatica sp. nov. Incorrect taxonomic identification of industrial contaminants is a problematic issue. Application and testing of our genomic workflow allowed the correct classification of 23 Bcc industrial strains, and also indicated that B. aenigmatica sp. nov. may have greater importance than B. lata as a contaminant species. Our study illustrates how the non-food manufacturing industry can harness whole-genome sequencing to better understand antimicrobial-resistant bacteria affecting their products.

scholarly journals An ex vivo cystic fibrosis model recapitulates key clinical aspects of chronic Staphylococcus aureus infection

Microbiology ◽  
2020 ◽  
Author(s):  
Esther Sweeney ◽  
Niamh E. Harrington ◽  
Alicia G. Harley Henriques ◽  
Marwa M. Hassan ◽  
Branagh Crealock-Ashurst ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Type Species ◽  
Ex Vivo ◽  
Clinical Aspects ◽  
Content Type ◽  
Link Type ◽  
Preferential Localization ◽  
Clinical Responses ◽  
Clinically Significant

Staphylococcus aureus is the most prevalent organism isolated from the airways of people with cystic fibrosis (CF), predominantly early in life. Yet its role in the pathology of lung disease is poorly understood. In mice, and many experiments using cell lines, the bacterium invades cells or interstitium, and forms abscesses. This is at odds with the limited available clinical data: interstitial bacteria are rare in CF biopsies and abscesses are highly unusual. Bacteria instead appear to localize in mucus plugs in the lumens of bronchioles. We show that, in an established ex vivo model of CF infection comprising porcine bronchiolar tissue and synthetic mucus, S. aureus demonstrates clinically significant characteristics including colonization of the airway lumen, with preferential localization as multicellular aggregates in mucus, initiation of a small colony variant phenotype and increased antibiotic tolerance of tissue-associated aggregates. Tissue invasion and abscesses were not observed. Our results may inform ongoing debates relating to clinical responses to S. aureus in people with CF.

scholarly journals Sequence diversity of the Pseudomonas aeruginosa population in loci that undergo microevolution in cystic fibrosis airways

2021 ◽  
Vol 3 (12) ◽  
Author(s):  
Sebastian Fischer ◽  
Jens Klockgether ◽  
Marina Gonzalez Sorribes ◽  
Marie Dorda ◽  
Lutz Wiehlmann ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Type Species ◽  
Sequence Diversity ◽  
Missense Mutations ◽  
Content Type ◽  
Synonymous Substitutions ◽  
Link Type ◽  
Human Infections ◽  
Coding Variants

Five hundred and thirty-four unrelated Pseudomonas aeruginosa isolates from inanimate habitats, patients with cystic fibrosis (CF) and other human infections were sequenced in 19 genes that had been identified previously as the hot spots of genomic within-host evolution in serial isolates from 12 CF lungs. Amplicon sequencing confirmed a significantly higher sequence diversity of the 19 loci in P. aeruginosa isolates from CF patients compared to those from other habitats, but this overrepresentation was mainly due to the larger share of synonymous substitutions. Correspondingly, non-synonymous substitutions were either rare (gltT, lepA, ptsP) or benign (nuoL, fleR, pelF) in some loci. Other loci, however, showed an accumulation of non-neutral coding variants. Strains from the CF habitat were often mutated at evolutionarily conserved positions in the elements of stringent response (RelA, SpoT), LPS (PagL), polyamine transport (SpuE, SpuF) and alginate biosynthesis (AlgG, AlgU). The strongest skew towards the CF lung habitat was seen for amino acid sequence variants in AlgG that clustered in the carbohydrate-binding/sugar hydrolysis domain. The master regulators of quorum sensing lasR and rhlR were frequent targets for coding variants in isolates from chronic and acute human infections. Unique variants in lasR showed strong evidence of positive selection indicated by d N/d S values of ~4. The pelA gene that encodes a multidomain enzyme involved in both the formation and dispersion of Pel biofilms carried the highest number of single-nucleotide variants among the 19 genes and was the only gene with a higher frequency of missense mutations in P. aeruginosa strains from non-CF habitats than in isolates from CF airways. PelA protein variants are widely distributed in the P. aeruginosa population. In conclusion, coding variants in a subset of the examined loci are indeed characteristic for the adaptation of P. aeruginosa to the CF airways, but for other loci the elevated mutation rate is more indicative of infections in human habitats (lasR, rhlR) or global diversifying selection (pelA).

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