The selective advantage of cystic fibrosis heterozygotes tested by aDNA analysis: A preliminary investigation

2000 ◽  
Vol 15 (3-4) ◽  
pp. 255-262 ◽  
Author(s):  
B. Bramanti ◽  
L. Sineo ◽  
M. Vianello ◽  
D. Caramelli ◽  
S. Hummel ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Preliminary Investigation ◽  
Selective Advantage ◽  
Adna Analysis

scholarly journals Cystic fibrosis carriership and tuberculosis: hints toward an evolutionary selective advantage based on data from the Brazilian territory

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Lander Bosch ◽  
Barbara Bosch ◽  
Kris De Boeck ◽  
Tim Nawrot ◽  
Isabelle Meyts ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Selective Advantage

scholarly journals Physiologic Evidence for the Efficacy of Positive Expiratory Pressure as an Airway Clearance Technique in Patients With Cystic Fibrosis

2004 ◽  
Vol 84 (6) ◽  
pp. 524-537 ◽  
Author(s):  
Joan C Darbee ◽  
Patricia J Ohtake ◽  
Brydon JB Grant ◽  
Frank J Cerny
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Vital Capacity ◽  
Preliminary Investigation ◽  
Therapeutic Modality ◽  
Gas Mixing ◽  
Ventilation Distribution ◽  
Single Breath ◽  
Arterial Blood ◽  
Positive Expiratory Pressure

Abstract Background and Purpose. Individuals with cystic fibrosis (CF) have large amounts of infected mucus in their lungs, which causes irreversible lung tissue damage. Although patient-administered positive expiratory pressure (PEP) breathing has been promoted as an effective therapeutic modality for removing mucus and improving ventilation distribution in these patients, the effects of PEP on ventilation distribution and gas mixing have not been documented. Therefore, this preliminary investigation described responses in distribution of ventilation and gas mixing to PEP breathing for patients with moderate to severe CF lung disease. Subjects and Methods. The effects of PEP breathing on ventilation distribution, gas mixing, lung volumes, expiratory airflow, percentage of arterial blood oxyhemoglobin saturation (Spo2), and sputum volume were studied in 5 patients with CF (mean age=18 years, SD=4, range=13–22) after no-PEP, low-PEP (10–20 cm H2O), and high-PEP (>20 cm H2O) breathing conditions. Single-breath inert gas studies and lung function tests were performed before, immediately after, and 45 minutes after intervention. Single-breath tests assess ventilation distribution homogeneity and gas mixing by observing the extent to which an inspired test gas mixes with gas already residing in the lung. Results. Improvements in gas mixing were observed in all PEP conditions. By 45 minutes after intervention, the no-PEP group improved by 5%, the low-PEP group improved by 15%, and the high-PEP group improved by 23%. Slow vital capacity increased by 1% for no PEP, by 9% for low PEP, and by 13% for high PEP 45 minutes after intervention. Residual volume decreased by 13% after no PEP, by 20% after low PEP, and by 30% after high PEP. Immediate improvements in forced expiratory flow during the middle half of the forced vital capacity maneuver (FEF25%–75%) were sustained following high PEP but not following low PEP. Discussion and Conclusion. This study demonstrated the physiologic basis for the efficacy of PEP therapy. The results confirm that low PEP and high PEP improve gas mixing in individuals with CF, and these improvements were associated with increased lung function, sputum expectoration, and SpO2. The authors propose that improvements in gas mixing may lead to increases in oxygenation and thus functional exercise capacity.

scholarly journals High Prevalence of Staphylococcus aureus Enterotoxin Gene Cluster Superantigens in Cystic Fibrosis Clinical Isolates

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 1036 ◽  
Author(s):  
Anthony J. Fischer ◽  
Samuel H. Kilgore ◽  
Sachinkumar B. Singh ◽  
Patrick D. Allen ◽  
Alexis R. Hansen ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Gene Cluster ◽  
Phenotypic Diversity ◽  
Selective Advantage ◽  
Clinical Isolates ◽  
Respiratory Pathogen ◽  
Enterotoxin Gene ◽  
Chronic Infections ◽  
Genotypic Analysis

Background: Staphylococcus aureus is a highly prevalent respiratory pathogen in cystic fibrosis (CF). It is unclear how this organism establishes chronic infections in CF airways. We hypothesized that S. aureus isolates from patients with CF would share common virulence properties that enable chronic infection. Methods: 77 S. aureus isolates were obtained from 45 de-identified patients with CF at the University of Iowa. We assessed isolates phenotypically and used genotyping assays to determine the presence or absence of 18 superantigens (SAgs). Results: We observed phenotypic diversity among S. aureus isolates from patients with CF. Genotypic analysis for SAgs revealed 79.8% of CF clinical isolates carried all six members of the enterotoxin gene cluster (EGC). MRSA and MSSA isolates had similar prevalence of SAgs. We additionally observed that EGC SAgs were prevalent in S. aureus isolated from two geographically distinct CF centers. Conclusions: S. aureus SAgs belonging to the EGC are highly prevalent in CF clinical isolates. The greater prevalence in these SAgs in CF airway specimens compared to skin isolates suggests that these toxins confer selective advantage in the CF airway.

scholarly journals Staphylococcus aureus and Cystic Fibrosis—A Close Relationship. What Can We Learn from Sequencing Studies?

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1177
Author(s):  
Christine Rumpf ◽  
Jonas Lange ◽  
Bianca Schwartbeck ◽  
Barbara C. Kahl
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Acquired Resistance ◽  
Selective Advantage ◽  
Whole Genome ◽  
Spa Typing ◽  
New Genes ◽  
Sequencing Studies

Staphylococcus aureus is next to Pseudomonas aeruginosa the most isolated pathogen from the airways of cystic fibrosis (CF) patients, who are often infected by a dominant S. aureus clone for extended periods. To be able to persist, the pathogen has to adapt to the hostile niche of the airways to counteract host defence, antibiotic therapy and the competition with coinfecting pathogens. S. aureus is equipped with many virulence factors including adhesins, toxins that are localized on the chromosome, on plasmids or are phage-related. S. aureus is especially versatile and adaptation and evolution of the pathogen occurs by the acquisition of new genes by horizontal gene transfer (HGT), changes in nucleotides (single nucleotide variations, SNVs) that can cause a selective advantage for the bacteria and become fixed in subpopulations. Methicillin-resistant S. aureus are a special threat to CF patients due to the more severe lung disease occurring in infected patients. Today, with decreasing costs for sequencing, more and more studies using S. aureus isolates cultured from CF patients are being published, which use whole genome sequencing (WGS), multilocus sequence typing (MLST) or spa-sequence typing (spa-typing) to follow the population dynamics of S. aureus, elucidate the underlying mechanisms of phenotypic variants, newly acquired resistance or adaptation to the host response in this particular niche. In the first part of this review, an introduction to the genetic make-up and the pathogenesis of S. aureus with respect to CF is provided. The second part presents an overview of recent studies and their findings using genotypic methods such as single or multilocus sequencing and whole genome sequencing, which identify factors contributing to the adaptation of S. aureus and its evolution in the airways of individuals with CF.

scholarly journals Autonomous sweat extraction and analysis applied to cystic fibrosis and glucose monitoring using a fully integrated wearable platform

2017 ◽  
Vol 114 (18) ◽  
pp. 4625-4630 ◽  
Author(s):  
Sam Emaminejad ◽  
Wei Gao ◽  
Eric Wu ◽  
Zoe A. Davies ◽  
Hnin Yin Yin Nyein ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Real Time ◽  
Preliminary Investigation ◽  
Glucose Monitoring ◽  
Glucose Consumption ◽  
Electrical Current ◽  
Sweat Glands ◽  
Oral Glucose ◽  
Clinical Value ◽  
Health States

Perspiration-based wearable biosensors facilitate continuous monitoring of individuals’ health states with real-time and molecular-level insight. The inherent inaccessibility of sweat in sedentary individuals in large volume (≥10 µL) for on-demand and in situ analysis has limited our ability to capitalize on this noninvasive and rich source of information. A wearable and miniaturized iontophoresis interface is an excellent solution to overcome this barrier. The iontophoresis process involves delivery of stimulating agonists to the sweat glands with the aid of an electrical current. The challenge remains in devising an iontophoresis interface that can extract sufficient amount of sweat for robust sensing, without electrode corrosion and burning/causing discomfort in subjects. Here, we overcame this challenge through realizing an electrochemically enhanced iontophoresis interface, integrated in a wearable sweat analysis platform. This interface can be programmed to induce sweat with various secretion profiles for real-time analysis, a capability which can be exploited to advance our knowledge of the sweat gland physiology and the secretion process. To demonstrate the clinical value of our platform, human subject studies were performed in the context of the cystic fibrosis diagnosis and preliminary investigation of the blood/sweat glucose correlation. With our platform, we detected the elevated sweat electrolyte content of cystic fibrosis patients compared with that of healthy control subjects. Furthermore, our results indicate that oral glucose consumption in the fasting state is followed by increased glucose levels in both sweat and blood. Our solution opens the possibility for a broad range of noninvasive diagnostic and general population health monitoring applications.

scholarly journals Establishment and equilibrium levels of deleterious mutations in large populations

2018 ◽  
Author(s):  
Johan W. Viljoen ◽  
J. Pieter de Villiers ◽  
Augustus J. Van Zyl ◽  
Massimo Mezzavilla ◽  
Michael S. Pepper
Keyword(s):  
Cystic Fibrosis ◽  
Social Relationships ◽  
Sickle Cell ◽  
Computer Modelling ◽  
Large Population ◽  
Selective Advantage ◽  
Human Populations ◽  
Deleterious Mutations ◽  
Effective Population ◽  
Community Size

AbstractAnalytical and statistical stochastic approaches are used to model and predict the dispersion of mutations through a large population. These approaches are used to quantify the magnitude of a heterozygous selective advantage of a mutation in the presence of a homozygous disadvantage. Random effects such as genetic drift are accounted for, which are likely to extinguish even highly advantageous mutations while the prevalence is still low. Dunbar’s results regarding the cognitive upper limit of the number of stable social relationships that humans can maintain are used to determine a realistic community size - a reduced local subset of the total population - from which an individual can select mates. This reduction in effective population size has a dramatic effect on the probability of establishing mutations, as well as the eventual equilibrium values that are reached in the case of mutations conferring a heterozygous selective advantage, but a homozygous disadvantage, as in the case of cystic fibrosis and sickle cell disease. The magnitude of this selective advantage can then be estimated based on observed occurrence levels of a specific mutation in a population, without requiring prior information regarding its phenotypic manifestation.Author summaryDeleterious mutations such as cystic fibrosis and sickle cell anemia can disperse through human populations due to the selective advantage that it bestows on heterozygous carriers, depending on environmental conditions. As its prevalence increases, the probability of generating homozygous offspring, with its concomitant selective disadvantage, also grows until an eventual equilibrium is reached between the number of carriers and wild-type individuals. In this work computer modelling is used to combine Dunbar’s anthropological observations predicting upper bounds to the number of stable human social relationships with observed prevalence levels, to estimate the absolute magnitude of the heterozygous selective advantage bestowed by such a deleterious genetic variation, without requiring knowledge regarding the specific mechanism whereby such an advantage is manifested.

scholarly journals Impact of High Diversity of Achromobacter Populations within Cystic Fibrosis Sputum Samples on Antimicrobial Susceptibility Testing

2016 ◽  
Vol 55 (1) ◽  
pp. 206-215 ◽  
Author(s):  
Chloé Dupont ◽  
Estelle Jumas-Bilak ◽  
Anne-Laure Michon ◽  
Raphaël Chiron ◽  
Hélène Marchandin
Keyword(s):  
Cystic Fibrosis ◽  
Antimicrobial Resistance ◽  
Sputum Sample ◽  
Adaptive Strategy ◽  
Opportunistic Pathogen ◽  
Selective Advantage ◽  
Genomic Diversity ◽  
Content Type ◽  
Airway Infections ◽  
Chronic Colonization

ABSTRACT Chronic colonization by opportunistic environmental bacteria is frequent in the airways of cystic fibrosis (CF) patients. Studies of Pseudomonas aeruginosa evolution during persistence have highlighted the emergence of pathoadaptive genotypes and phenotypes, leading to complex and diversified inpatient colonizing populations also observed at the intraspecimen level. Such diversity, including heterogeneity in resistance profiles, has been considered an adaptive strategy devoted to host persistence. Longitudinal genomic diversity has been shown for the emergent opportunistic pathogen Achromobacter , but phenotypic and genomic diversity has not yet been studied within a simple CF sputum sample. Here, we studied the genomic diversity and antimicrobial resistance heterogeneity of 132 Achromobacter species strains (8 to 27 strains of identical or distinct colonial morphotypes per specimen) recovered from the sputum samples of 9 chronically colonized CF patients. We highlighted the high within-sample and within-morphotype diversity of antimicrobial resistance (disk diffusion) and genomic (pulsed-field gel electrophoresis) profiles. No sputum sample included strains with identical pulsotypes or antibiotic susceptibility patterns. Differences in clinical categorization were observed for the 9 patients and concerned 3 to 11 antibiotics, including antibiotics recommended for use against Achromobacter . Within-sample antimicrobial resistance heterogeneity, not predictable from colonial morphology, suggested that it may represent a selective advantage against antibiotics in an Achromobacter persisting population and potentially compromise the antibiotic management of CF airway infections.

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