scholarly journals MRSA Strains with Distinct Accessory Genes Predominate at Different Ages in Cystic Fibrosis

2021 ◽  
Author(s):  
Harry S. Porterfield ◽  
Lucas J. Maakestad ◽  
Mason M. LaMarche ◽  
Andrew L. Thurman ◽  
Zoe E. Kienenberger ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Accessory Genes ◽  
Different Ages ◽  
Mrsa Strains

scholarly journals MRSA Strains with Distinct Accessory Genes Predominate at Different Ages in Cystic Fibrosis

2021 ◽  
Author(s):  
Harry Porterfield ◽  
Lucas Maakestad ◽  
Mason LaMarche ◽  
Andrew Thurman ◽  
Zoe Kienenberger ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Gene Content ◽  
Accessory Gene ◽  
Younger Patients ◽  
Accessory Genome ◽  
Accessory Genes ◽  
Different Ages ◽  
Mrsa Strains ◽  
Genome Assemblies ◽  
Reference Genomes

Rationale: Methicillin resistant Staphylococcus aureus (MRSA) is prevalent and consequential in cystic fibrosis (CF). Whole genome sequencing (WGS) could reveal genomic differences in MRSA associated with poorer outcomes or detect MRSA transmission. Objectives: To identify MRSA genes associated with low lung function and identify potential MRSA transmission in CF. Methods: We collected 97 MRSA isolates from 74 individuals with CF from 2017 and performed short-read WGS. We determined sequence type (ST) and the phylogenetic relationship between isolates. We aligned accessory genes from 25 reference genomes to genome assemblies. We classified the MRSA by accessory gene content and correlated the accessory genome to clinical outcomes. Results: The most prevalent ST were ST5 (N=55), ST105 (N=14), and ST8 (N=14). Closely related MRSA strains were shared by family members with CF, but rarely between unrelated individuals. Three distinct clusters of MRSA were identified by accessory genome content. The first included ST5 and ST105 strains and was common among older patients with lower FEV. The second cluster included ST8, which was generally identified in younger patients. Sputum density of MRSA and Pseudomonas aeruginosa was higher in cultures from patients with ST5/ST105 compared to patients with ST8 at similar ages. Conclusions: In this CF cohort, we identified MRSA subtypes that predominate at different ages and differ by accessory gene content. ST5 and ST105 represented the most prevalent cluster of MRSA. ST8 MRSA was more common in younger patients and thus has the potential to rise in prevalence as these patients age.

Significant differences in type IV pilin allele distribution among Pseudomonas aeruginosa isolates from cystic fibrosis (CF) versus non-CF patients

Microbiology ◽  
2004 ◽  
Vol 150 (5) ◽  
pp. 1315-1326 ◽  
Author(s):  
Julianne V. Kus ◽  
Elizabeth Tullis ◽  
Dennis G. Cvitkovitch ◽  
Lori L. Burrows
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Opportunistic Pathogen ◽  
Host Cells ◽  
Phylogenetic Groups ◽  
Allele Distribution ◽  
Specific Pcr ◽  
Type Iv ◽  
Accessory Genes ◽  
Group I

Type IV pili (TFP) are important colonization factors of the opportunistic pathogen Pseudomonas aeruginosa, involved in biofilm formation and attachment to host cells. This study undertook a comprehensive analysis of TFP alleles in more than 290 environmental, clinical, rectal and cystic fibrosis (CF) isolates of P. aeruginosa. Based on the results, a new system of nomenclature is proposed, in which P. aeruginosa TFP are divided into five distinct phylogenetic groups. Each pilin allele is stringently associated with characteristic, distinct accessory genes that allow the identification of the allele by specific PCR. The invariant association of the pilin and accessory genes implies horizontal transfer of the entire locus. Analysis of pilin allele distribution among isolates from various sources revealed a striking bias in the prevalence of isolates with group I pilin genes from CF compared with non-CF human sources (P<0·0001), suggesting this particular pilin type, which can be post-translationally modified by glycosylation via the action of TfpO (PilO), may confer a colonization or persistence advantage in the CF host. This allele was also predominant in paediatric CF isolates (29 of 43; 67·4 %), showing that this bias is apparent early in colonization. Group I pilins were also the most common type found in environmental isolates tested. To the authors' knowledge, this is the first example of a P. aeruginosa virulence factor allele that is strongly associated with CF isolates.

scholarly journals Emergence and Within-Host Genetic Evolution of Methicillin-ResistantStaphylococcus aureusResistant to Linezolid in a Cystic Fibrosis Patient

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
Caroline Rouard ◽  
Fabien Garnier ◽  
Jeremy Leraut ◽  
Margaux Lepainteur ◽  
Lalaina Rahajamananav ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Generation Time ◽  
Strong Increase ◽  
Whole Genome ◽  
Content Type ◽  
Mrsa Infection ◽  
Host Genetic ◽  
Mrsa Strains

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) infection has increased in recent years among cystic fibrosis (CF) patients. Linezolid (LZD) is one of the antistaphylococcal antibiotics widely used in this context. Although LZD resistance is rare, it has been described as often associated with long-term treatments. Thirteen MRSA strains isolated over 5 years from one CF patient were studied for LZD resistance emergence and subjected to whole-genome sequencing (WGS). Resistance emerged after three 15-day LZD therapeutic regimens over 4 months. It was associated with the mutation of G to T at position 2576 (G2576T) in all 5rrlcopies, along with a very high MIC (>256 mg/liter) and a strong increase in the generation time. Resistant strains isolated during the ensuing LZD therapeutic regimens and until 13 months after LZD stopped harbored only 3 or 4 mutatedrrlcopies, associated with lower MICs (8 to 32 mg/liter) and low to moderate generation time increases. Despite these differences, whole-genome sequencing allowed us to determine that all isolates, including the susceptible one isolated before LZD treatment, belonged to the same lineage. In conclusion, LZD resistance can emerge rapidly in CF patients and persist without linezolid selective pressure in colonizing MRSA strains belonging to the same lineage.

scholarly journals Telavancin Displays Activity Against Cystic Fibrosis-Associated MRSA Strains Including Those With Increased Resistance to Ceftaroline

2016 ◽  
Vol 3 (suppl_1) ◽  
Author(s):  
Melanie Roch ◽  
Maria Pilar Martinez ◽  
Maryam Fatouraei ◽  
Warren Rose ◽  
Rafael Hernandez ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Mrsa Strains

scholarly journals In VitroActivity of Fusidic Acid (CEM-102, Sodium Fusidate) against Staphylococcus aureus Isolates from Cystic Fibrosis Patients and Its Effect on the Activities of Tobramycin and Amikacin against Pseudomonas aeruginosa and Burkholderia cepacia

2011 ◽  
Vol 55 (5) ◽  
pp. 2417-2419 ◽  
Author(s):  
Pamela McGhee ◽  
Catherine Clark ◽  
Kim Credito ◽  
Linda Beachel ◽  
Glenn A. Pankuch ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Protein Binding ◽  
Fusidic Acid ◽  
Burkholderia Cepacia ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mrsa Strains ◽  
Time Kill

ABSTRACTWe tested the MICs of fusidic acid (CEM-102) plus other agents against 40 methicillin-resistantStaphylococcus aureus(MRSA) isolates from cystic fibrosis patients and the activities of fusidic acid with or without tobramycin or amikacin againstPseudomonas aeruginosa, MRSA, andBurkholderia cepaciaisolates from cystic fibrosis patients in a 24-h time-kill study. Fusidic acid was potent (MICs, 0.125 to 0.5 μg/ml; a single 500-mg dose of fusidic acid at 8 h averaged 8 to 12. 5 μg/ml with 91 to 97% protein binding) against all MRSA strains. No antagonism was observed; synergy occurred for one MRSA strain treated with fusidic acid plus tobramycin.

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 Bactericidal and Fungicidal Activity of N-Chlorotaurine Is Enhanced in Cystic Fibrosis Sputum Medium

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Martina Gruber ◽  
Ivan Moser ◽  
Markus Nagl ◽  
Michaela Lackner
Keyword(s):  
Cystic Fibrosis ◽  
Fungicidal Activity ◽  
Buffer Solution ◽  
Multiresistant Pathogens ◽  
Content Type ◽  
Microbicidal Activity ◽  
Development Of Resistance ◽  
Mrsa Strains ◽  
Time Kill

ABSTRACT Lung infections with multiresistant pathogens are a major problem among patients suffering from cystic fibrosis (CF). N-Chlorotaurine (NCT), a microbicidal active chlorine compound with no development of resistance, is well tolerated upon inhalation. The aim of this study was to investigate the in vitro bactericidal and fungicidal activity of NCT in artificial sputum medium (ASM), which mimics the composition of CF mucus. The medium was inoculated with bacteria (Staphylococcus aureus, including some methicillin-resistant S. aureus [MRSA] strains, Pseudomonas aeruginosa, and Escherichia coli) or spores of fungi (Aspergillus fumigatus, Aspergillus terreus, Candida albicans, Scedosporium apiospermum, Scedosporium boydii, Lomentospora prolificans, Scedosporium aurantiacum, Scedosporium minutisporum, Exophiala dermatitidis, and Geotrichum sp.), to final concentrations of 107 to 108 CFU/ml. NCT was added at 37°C, and time-kill assays were performed. At a concentration of 1% (10 mg/ml, 55 mM) NCT, bacteria and spores were killed within 10 min and 15 min, respectively, to the detection limit of 102 CFU/ml (reduction of 5 to 6 log10 units). Reductions of 2 log10 units were still achieved with 0.1% (bacteria) and 0.3% (fungi) NCT, largely within 10 to 30 min. Measurements by means of iodometric titration showed oxidizing activity for 1, 30, 60, and >60 min at concentrations of 0.1%, 0.3%, 0.5%, and 1.0% NCT, respectively, which matches the killing test results. NCT demonstrated broad-spectrum microbicidal activity in the milieu of CF mucus at concentrations ideal for clinical use. The microbicidal activity of NCT in ASM was even stronger than that in buffer solution; this was particularly pronounced for fungi. This finding can be explained largely by the formation, through transhalogenation, of monochloramine, which rapidly penetrates pathogens.

Pregnancy in cystic fibrosis of the pancreas

JAMA ◽  
1966 ◽  
Vol 195 (12) ◽  
pp. 993-1000 ◽  
Author(s):  
R. J. Grand
Keyword(s):  
Cystic Fibrosis
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