Adv Sci (Weinh). 2022 Oct 10:e2202556. doi: 10.1002/advs.202202556. Online ahead of print.

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause lethal pulmonary damage in humans. It contains spike proteins on its envelope that bind to human angiotensin-converting enzyme 2 (hACE2) expressed on airway cells, enabling entry of the virus, and causing infection. The soluble form of hACE2 binds SARS-CoV-2 spike protein, prevents viral entry into target cells, and ameliorates lung injury; however, its short half-life limits therapeutic utilities. Here, synthetic mRNA is engineered to encode a soluble form of hACE2 (hsACE2) to prevent viral infection. A novel lipid nanoparticle (LNP) is used for packaging and delivering mRNA to cells to produce hsACE2 proteins. Intravenously administered LNP delivers mRNA to hepatocytes, leading to the production of circulatory hsACE2 initiated within 2 h and sustained over several days. Inhaled LNP results in lung transfection and secretion of mucosal hsACE2 to lung epithelia, the primary site of entry and pathogenesis for SARS-CoV-2. Furthermore, mRNA-generated hsACE2 binds to the receptor-binding domain of the viral spike protein. Finally, hsACE2 effectively inhibits SARS-CoV-2 and its pseudoviruses from infecting host cells. The proof of principle study shows that mRNA-based nanotherapeutics can be potentially deployed to neutralize SARS-CoV-2 and open new treatment opportunities for coronavirus disease 2019 (COVID-19).

PMID:36216580 | DOI:10.1002/advs.202202556

Cell Signal. 2022 Oct 7:110489. doi: 10.1016/j.cellsig.2022.110489. Online ahead of print.

ABSTRACT

Vibrio cholerae colonizes the small intestine and releases cholera toxin into the extracellular space. The toxin binds to the apical surface of the epithelium, is internalized into the host endomembrane system, and escapes into the cytosol where it activates the stimulatory alpha subunit of the heterotrimeric G protein by ADP-ribosylation. This initiates a cAMP-dependent signaling pathway that stimulates chloride efflux into the gut, with diarrhea resulting from the accompanying osmotic movement of water into the intestinal lumen. G protein signaling is not the only host system manipulated by cholera toxin, however. Other cellular mechanisms and signaling pathways active in the intoxication process include endocytosis through lipid rafts, retrograde transport to the endoplasmic reticulum, the endoplasmic reticulum-associated degradation system for protein delivery to the cytosol, the unfolded protein response, and G protein de-activation through degradation or the function of ADP-ribosyl hydrolases. Although toxin-induced chloride efflux is thought to be an irreversible event, alterations to these processes could facilitate cellular recovery from intoxication. This review will highlight how cholera toxin exploits signaling pathways and other cell biology events to elicit a diarrheal response from the host.

PMID:36216164 | DOI:10.1016/j.cellsig.2022.110489

ACS Chem Biol. 2022 Oct 10. doi: 10.1021/acschembio.2c00529. Online ahead of print.

ABSTRACT

Opportunistic infections by Burkholderia cenocepacia are life threatening for patients suffering from cystic fibrosis and chronic granulomatous disease. These infections are often associated with variable clinical outcomes, prompting an interest in molecular investigations of phenotypes associated with disease severity. The production of the pyomelanin pigment is one such phenotype, which was recently linked to the ability of clinical strains to carry out biotransformation of the antibiotic trimethoprim. However, this biotransformation product was not identified, and differences in metabolite production associated with pyomelanin pigmentation are poorly understood. Here, we identify several key metabolites produced exclusively by the pyomelanin-producing strains. To provide insight into the structures and biosynthetic origin of these metabolites, we developed a mass spectrometry-based strategy coupling unsupervised in silico substructure prediction with stable isotope labeling referred to as MAS-SILAC (Metabolite Annotation assisted by Substructure discovery and Stable Isotope Labeling by Amino acids in Cell culture). This approach led to discovery of homogentisic acid as a precursor for biosynthesis of several natural products and for biotransformation of trimethoprim, representing a previously unknown mechanism of antibiotic tolerance. This work presents application of computational methods for analysis of untargeted metabolomic data to link the chemotype of pathogenic microorganisms with a specific phenotype. The observations made in this study provide insights into the clinical significance of the melanated phenotype.

PMID:36215670 | DOI:10.1021/acschembio.2c00529

Biometals. 2022 Oct 10. doi: 10.1007/s10534-022-00453-x. Online ahead of print.

ABSTRACT

Iron is by far the most widespread and essential transition metal, possessing crucial biological functions for living systems. Despite chemical advantages, iron biology has forced organisms to face with some issues: ferric iron insolubility and ferrous-driven formation of toxic radicals. For these reasons, acquisition and transport of iron constitutes a formidable challenge for cells and organisms, which need to maintain adequate iron concentrations within a narrow range, allowing biological processes without triggering toxic effects. Higher organisms have evolved extracellular carrier proteins to acquire, transport and manage iron. In recent years, a renewed interest in iron biology has highlighted the role of iron-proteins dysregulation in the onset and/or exacerbation of different pathological conditions. However, to date, no resolutive therapy for iron disorders has been found. In this review, we outline the efficacy of Lactoferrin, a member of the transferrin family mainly secreted by exocrine glands and neutrophils, as a new emerging orchestrator of iron metabolism and homeostasis, able to counteract iron disorders associated to different pathologies, including iron deficiency and anemia of inflammation in blood, Parkinson and Alzheimer diseases in the brain and cystic fibrosis in the lung.

PMID:36214975 | DOI:10.1007/s10534-022-00453-x

Oncoimmunology. 2022 Oct 4;11(1):2131227. doi: 10.1080/2162402X.2022.2131227. eCollection 2022.

NO ABSTRACT

PMID:36211810 | PMC:PMC9542269 | DOI:10.1080/2162402X.2022.2131227

Oncoimmunology. 2022 Sep 30;11(1):2130558. doi: 10.1080/2162402X.2022.2130558. eCollection 2022.

NO ABSTRACT

PMID:36211809 | PMC:PMC9542941 | DOI:10.1080/2162402X.2022.2130558

J Cyst Fibros. 2022 Oct 6:S1569-1993(22)00690-7. doi: 10.1016/j.jcf.2022.09.013. Online ahead of print.

ABSTRACT

BACKGROUND: As survival and health improve in people with cystic fibrosis (CF), more women with CF (wwCF) are considering their sexual and reproductive health (SRH). This study compared SRH experiences, behaviors, and care utilization of wwCF to the general population and defined CF-impacted considerations and care preferences.

METHODS: We surveyed wwCF aged ≥25 years regarding SRH and compared results to the US National Survey of Family Growth (NSFG;n = 4357) and friend controls(n = 123). We used descriptive statistics and chi-squared/Fisher's exact testing and linear regression for comparisons.

RESULTS: A total of 460 wwCF (mean age 36.1 years) completed the survey. WwCF were less likely to report current contraceptive use (43%vs76% NSFG, p<0.001;60% friends, p = 0.005). Nearly 25% of wwCF reported worsened CF symptoms during their menstrual cycles, 50% experienced urinary incontinence, and 80% vulvovaginal candidiasis. WwCF were significantly less likely to be parents (46%vs62% friends, p = 0.015) and to have experienced pregnancy (37%vs78% NSFG, p<0.001;58% friends, p = 0.002). More wwCF required medical assistance to conceive (29%vs12% NSFG, p<0.001 and 5% friends, p<0.001). Eighty-four percent of wwCF view their CF doctor as their main physician and 41% report no primary care provider (vs19% friends; p<0.001). WwCF report suboptimal rates of contraceptive and preconception counseling/care and are less likely to have received HPV vaccination (42%vs55%friends, p = 0.02). Despite desiring SRH conversations with their CF team, <50% report discussing SRH topics.

CONCLUSION: WwCF have significantly different SRH experiences than non-CF peers. They report suboptimal SRH care compared to their preferences highlighting an urgent need to encourage SRH counseling/care in the CF model.

PMID:36210323 | DOI:10.1016/j.jcf.2022.09.013

J Cyst Fibros. 2022 Oct 6:S1569-1993(22)00686-5. doi: 10.1016/j.jcf.2022.09.008. Online ahead of print.

ABSTRACT

Children and young people with CF (CYPwCF) get advice about using positive expiratory pressure (PEP) or oscillating PEP (OPEP) devices to clear sticky mucus from their lungs. However, little is known about the quantity (number of treatments, breaths, or sets) or quality (breath pressures and lengths) of these daily airway clearance techniques (ACTs) undertaken at home. This study used electronic pressure sensors to record real time breath-by-breath data from 145 CYPwCF (6-16y) during routine ACTs over 2 months. ACT quantity and quality were benchmarked against individual prescriptions and accepted recommendations for device use. In total 742,084 breaths from 9,081 treatments were recorded. Individual CYPwCF maintained consistent patterns of ACT quantity and quality over time. Overall, 60% of CYPwCF did at least half their prescribed treatments, while 27% did fewer than a quarter. About 77% of pre-teens did the right number of daily treatments compared with only 56% of teenagers. CYPwCF usually did the right number of breaths. ACT quality (recommended breath length and pressure) varied between participants and depended on device. Breath pressures, lengths and pressure-length relationships were significantly different between ACT devices. PEP devices encouraged longer breaths with lower pressures, while OPEP devices encouraged shorter breaths with higher pressures. More breaths per treatment were within advised ranges for both pressure and length using PEP (30-31%) than OPEP devices (1-3%). Objective measures of quantity and quality may help to optimise ACT device selection and support CYPwCF to do regular effective ACTs.

PMID:36210322 | DOI:10.1016/j.jcf.2022.09.008

J Biol Chem. 2022 Oct 6:102569. doi: 10.1016/j.jbc.2022.102569. Online ahead of print.

ABSTRACT

The nuclear bile acid receptor, farnesoid X receptor (FXR), is an important regulator of intestinal and metabolic function. Previous studies suggest that pentacyclic triterpenes (PCTs), a class of plant-derived bioactive phytochemical, can modulate FXR activity and may therefore offer therapeutic benefits. Here, we investigated the effects of a prototypical PCT, hederagenin (HG), on FXR expression, activity, and anti-secretory actions in colonic epithelial cells. T84 cells and murine enteroid-derived monolayers (EDMs) were employed to assess HG effects on FXR expression and activity in colonic epithelia. We measured mRNA levels by qRT-PCR and protein by ELISA and immunoblotting. Transepithelial Cl- secretion was assessed as changes in short-circuit current in Ussing chambers. We determined HG treatment (5 - 10 μM) alone did not induce FXR activation but significantly increased expression of the receptor, both in T84 cells and murine EDMs. This effect was accompanied by enhanced FXR activity, as assessed by FGF-15/19 induction in response to the synthetic, GW4064, or natural FXR agonist, chenodeoxycholic acid. Effects of HG on FXR expression and activity were mimicked by another PCT, oleanolic acid. Furthermore, we found FXR-induced downregulation of cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels and inhibition of transepithelial Cl- secretion were enhanced in HG-treated cells. These data demonstrate that dietary PCTs have the capacity to modulate FXR expression, activity, and anti-secretory actions in colonic epithelial cells. Based on these data, we propose that plants rich in PCTs, or extracts thereof, have excellent potential for development as a new class of "FXR-targeted nutraceuticals".

PMID:36209824 | DOI:10.1016/j.jbc.2022.102569

Surg Clin North Am. 2022 Oct;102(5):873-882. doi: 10.1016/j.suc.2022.07.016. Epub 2022 Sep 7.

ABSTRACT

Cystic fibrosis is an autosomal-recessive defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene located on chromosome 7 that affects 1 in 2500 live White births. Defects in the gene lead to abnormally thick secretions causing chronic obstruction in the respiratory and gastrointestinal tracts. Common gastrointestinal pathology in children with cystic fibrosis includes meconium ileus in infancy and distal intestinal obstruction syndrome in childhood and exocrine pancreatic insufficiency, constipation, and rectal prolapse. This article describes the presentation, diagnosis, and management of these conditions in patients with cystic fibrosis, from birth to adulthood.

PMID:36209752 | DOI:10.1016/j.suc.2022.07.016

Sci Rep. 2022 Oct 8;12(1):16941. doi: 10.1038/s41598-022-21478-9.

ABSTRACT

We evaluate the difference in vulnerability to desiccating stress (DS) between the corneal and conjunctival epithelia to understand different ocular surface staining patterns in dry eye patients. We generated a rabbit model of short-term exposure keratopathy. To induce DS in the ocular surface, rabbit right eyelids were opened for 30 min, with blinking once/minute. Corneal staining scores increased from 3-min post-DS exposure, while conjunctival staining increased from 20-min post-DS. At 20 min, the tear MUC5AC level doubled as compared to pre-DS (p = 0.007). In Western blot analysis, conjunctival AQP5, MUC5AC, and CFTR expression increased significantly in response to DS, compared to control (p = 0.039, 0.002, 0.039, respectively). Immunohistochemistry for CD31 and LYVE-1 were performed. CD31-positive cells and lymphatic space surrounded by LYVE-1-positive cells increased significantly in conjunctival tissue post-DS, compared to control (p = 0.0006, p < 0.0001, respectively). Surface damage was worse in the corneal than in the conjunctival epithelium after DS, by scanning electron microscopy. This study showed that the cornea and conjunctival epithelium show differences in vulnerability to DS. Increased blood vessels and dilated lymphatics, accompanied by increased conjunctival epithelial AQP5, MUC5AC, and CFTR expression, underlie the protective mechanism of the conjunctiva to desiccating stress.

PMID:36209216 | PMC:PMC9547869 | DOI:10.1038/s41598-022-21478-9

Curr Microbiol. 2022 Oct 8;79(11):353. doi: 10.1007/s00284-022-03048-4.

ABSTRACT

Pseudomonas aeruginosa has a high adaptive capacity, favoring the selection of antibiotic-resistant strains, which are currently considered a global health problem. The purpose of this work was to investigate the rate and distribution of extensively drug-resistant (XDR) P. aeruginosa in pediatric patients with cystic fibrosis (CF) with recurrent infections and to distinguish the current efficacy of antibiotics commonly used in eradication therapy at a Mexican institute focused on children. A total of 118 P. aeruginosa isolates from 25 children with CF (2015-2019) underwent molecular identification, antimicrobial sensitivity tests, and Random Amplified Polymorphic DNA genotyping (RAPD-PCR). The bacterial isolates were grouped in 84 RAPD profiles, revealing a cross-infection between two sisters, whose resistance profile remained unchanged for more than 2 years. Furthermore, 77.1% (91/118) and 51.7% (61/118) of isolates showed in vitro susceptibility to ceftazidime and amikacin, respectively, antibiotics often used in eradication therapy at our institution. As well, 42.4% (50/118) were categorized as multi-drug resistant (MDR) and 12.7% (15/118) were XDR. Of these resistant isolates, 84.6% (55/65) were identified from patients with recurrent infections. The high frequency of XDR strains in children with CF should be considered a caution mark, as such resistance patterns are more commonly found in adult patients. Additionally, amikacin may soon prove ineffective. Careful use of available antibiotics is crucial before therapeutic possibilities are reduced and "antibiotic resistance crisis" worsens.

PMID:36209248 | DOI:10.1007/s00284-022-03048-4

Sci Rep. 2022 Oct 7;12(1):16814. doi: 10.1038/s41598-022-21101-x.

ABSTRACT

Multidrug resistant (MDR) P. aeruginosa accounts for 35% of all P. aeruginosa isolated from respiratory samples of patients with cystic fibrosis (CF). The usefulness of β-lactam antibiotics for treating CF, such as carbapenems and later generation cephalosporins, is limited by the development of antibacterial resistance. A proven treatment approach is the combination of a β-lactam antibiotic with a β-lactamase inhibitor. New β-lactam/β-lactamase inhibitor combinations are available, but data are lacking regarding the susceptibility of MDR CF-associated P. aeruginosa (CFPA) to these new combination therapies. In this study we determined MIC values for three new combinations; imipenem-relebactam (I-R), ceftazidime-avibactam (CZA), and ceftolozane-tazobactam (C/T) against MDR CFPA (n = 20). The MIC90 of I-R, CZA, and C/T was 64/4, 32/4, and 16/8 (all µg/mL), respectively. The susceptibility of isolates to imipenem was not significantly improved with the addition of relebactam (p = 0.68). However, susceptibility to ceftazidime was significantly improved with the addition of avibactam (p < 0.01), and the susceptibility to C/T was improved compared to piperacillin/tazobactam (p < 0.05) These data provide in vitro evidence that I-R may not be any more effective than imipenem monotherapy against MDR CFPA. The pattern of susceptibility observed for CZA and C/T in the current study was similar to data previously reported for non-CF-associated MDR P. aeruginosa.

PMID:36207358 | DOI:10.1038/s41598-022-21101-x

J Cyst Fibros. 2022 Oct 5:S1569-1993(22)00684-1. doi: 10.1016/j.jcf.2022.09.005. Online ahead of print.

ABSTRACT

The spectrum of disorders involving CFTR (cystic fibrosis transmembrane conductance regulator) dysfunction correlates with a continuous gradient of CFTR function defined by the combination of two allelic CFTR variants. CFTR-related disorders are clinical entities with features of cystic fibrosis (CF) and evidence for presence of CFTR dysfunction but not meeting criteria for diagnosis of CF. Individuals with CFTR-RDs demonstrate a wide range of CFTR activity and are still under-recognized or misclassified. The level of CFTR dysfunction may be measured in vivo (sweat testing, nasal potential difference measurements) and/or by ex vivo tests (intestinal current measurement), or indirectly indicated by CFTR variants, as alteration in sequence of the CFTR gene translates into CFTR dysfunction. CFTR bioassays can aid in the diagnosis of individuals with CF, but we lack parameters to differentiate CF from CFTR-RD. In the era of the CFTR modulators and their potential clinical benefit, it is of utmost importance to diagnose CFTR-RD as unambiguously as possible. We therefore propose the following to define compatible CFTR dysfunction in a person with a suspected diagnosis of CFTR-RD : (1) evidence of CFTR dysfunction in vivo or ex vivo in at least two different CFTR functional test types, or (2) One CFTR variant known to reduce CFTR function and evidence of CFTR dysfunction in vivo or ex vivo in at least two different CFTR functional test types, or (3) Two CFTR variants shown to reduce CFTR function, with at most one CF-causing variant.

PMID:36207272 | DOI:10.1016/j.jcf.2022.09.005

Pediatr Clin North Am. 2022 Oct;69(5):951-963. doi: 10.1016/j.pcl.2022.05.008.

ABSTRACT

Pediatric chronic lung diseases burden their patients and families with heavy treatment loads, frequent extensive clinic visits to multiple providers, frequent emergency department visits and hospitalizations, and contribute to significant psychosocial issues with caregiver's burnout. The purpose of this chapter is to outline the psychosocial impact of the major pediatric chronic lung diseases and the unique role of the psychologist in relieving this burden. These include severe asthma, cystic fibrosis, bronchopulmonary dysplasia, and dependence on home mechanical ventilation.

PMID:36207105 | DOI:10.1016/j.pcl.2022.05.008

BMJ Open Respir Res. 2022 Oct;9(1):e001420. doi: 10.1136/bmjresp-2022-001420.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a genetic condition caused by variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that primarily impacts the lungs. Treatments historically have been symptomatic to improve airway clearance and treat infection. However, CFTR modulator drugs have recently been developed that target the underlying defect. The triple combination of elexacaftor-tezacaftor-ivacaftor (ETI) was approved in 2020 in England for over 80% of people with CF aged over 12 years and in 2022 extended to those over 6 years. ETI treatment is associated with substantial improvements in lung function. The experience of children with CF starting on ETI or their views regarding future treatments have not been well studied. This study aimed to explore the opinions of children with CF, their parents/carers and healthcare professionals (HCPs) on the impact of ETI, airway clearance techniques (ACTs) and nebulised treatments.

METHODS: Semistructured qualitative interviews were performed with 10 children with CF, 7 parents/carers and 10 HCPs. Audio recordings were transcribed and analysed using reflexive thematic analysis.

RESULTS: Four main themes were identified: 'Kaftrio changed my life', 'Your entire life is dictated by the CF timetable', 'Simplifying treatment-hopes and fears' and 'Kaftrio is a game-changer' along with several subthemes and an overarching theme of 'I still can't get my head around how three tablets can do what Kaftrio done'.

CONCLUSIONS: Despite the highly positive impact of ETI on the health of children with CF some concerns remain about the longer-term outcomes of reducing ACTs or nebulised treatments. ETI has prompted a shift in treatment for many and offers an opportunity to personalise approaches.

PMID:36207030 | DOI:10.1136/bmjresp-2022-001420

Respir Physiol Neurobiol. 2022 Oct 4:103976. doi: 10.1016/j.resp.2022.103976. Online ahead of print.

ABSTRACT

BACKGROUND: In patients with cystic fibrosis (CF), thoracic morphology and its role in respiratory function is conditioned by anthropometric factors, as well as by pathological changes. While the lungs are continuously monitored, examinations of potential thoracic cage adaptations to the disease are rare. Hence, the aim of this study was to investigate thoracic configuration, and its correlation to spirometry measures over time.

METHODS: In total, 344 high-resolution computed tomography (HRCT) examinations from 90 patients were assessed and analysed. Those results were subsequently related to spirometry measurements performed within the same period.

RESULTS: The cohort displayed no homogenous change in thoracic configuration over time, and correlation between thoracic area and spirometry variables could not be supported statistically.

CONCLUSIONS: Although the current study included a larger cohort of patients with CF compared to previous studies on thoracic morphology, no patient group-specific changes in thoracic configuration were revealed. Furthermore, no correlations between structural findings and functional respiratory measurements were found.

PMID:36206973 | DOI:10.1016/j.resp.2022.103976

Am J Hum Genet. 2022 Oct 6;109(10):1894-1908. doi: 10.1016/j.ajhg.2022.09.004.

ABSTRACT

Individuals with cystic fibrosis (CF) develop complications of the gastrointestinal tract influenced by genetic variants outside of CFTR. Cystic fibrosis-related diabetes (CFRD) is a distinct form of diabetes with a variable age of onset that occurs frequently in individuals with CF, while meconium ileus (MI) is a severe neonatal intestinal obstruction affecting ∼20% of newborns with CF. CFRD and MI are slightly correlated traits with previous evidence of overlap in their genetic architectures. To better understand the genetic commonality between CFRD and MI, we used whole-genome-sequencing data from the CF Genome Project to perform genome-wide association. These analyses revealed variants at 11 loci (6 not previously identified) that associated with MI and at 12 loci (5 not previously identified) that associated with CFRD. Of these, variants at SLC26A9, CEBPB, and PRSS1 associated with both traits; variants at SLC26A9 and CEBPB increased risk for both traits, while variants at PRSS1, the higher-risk alleles for CFRD, conferred lower risk for MI. Furthermore, common and rare variants within the SLC26A9 locus associated with MI only or CFRD only. As expected, different loci modify risk of CFRD and MI; however, a subset exhibit pleiotropic effects indicating etiologic and mechanistic overlap between these two otherwise distinct complications of CF.

PMID:36206743 | DOI:10.1016/j.ajhg.2022.09.004

Pediatr Transplant. 2022 Oct 7:e14404. doi: 10.1111/petr.14404. Online ahead of print.

ABSTRACT

BACKGROUND: CFTR modulators, especially (elexacaftor/tezacaftor/ivacaftor), have positively impacted the CF population and quickly decreased LTx numbers. However, no study has investigated if this reduction is universal across all races/ethnicities.

METHODS: Using the UNOS Registry, we explored the frequency/proportions of LTx in WNH and NW (Black, non-Hispanic/Hispanic-Latino/Asian-non Hispanic/American Indian-Alaskan Native-non-Hispanic/Native Hawaiian/Other Pacific Islander-non-Hispanic/Multiracial) in children and adults with CF in the US.

RESULTS: Between 1990 and 2019, the annual mean (±SD) number of LTxs for children with CF was 23.2 (±7.7) compared to 5 in 2020 (p < .001) and in 2021 (p < .001). In adults from 1990 to 2019, the mean (±SD) number of LTxs performed was 144.9 (±73.5), which was significantly higher than 2020 (n = 73; p < .001) and 2021 (n = 45; p < .001). Comparing 1990-2019 to post-2019, the proportion of LTxs performed in both children and adults with CF has decreased from 50.5% (696/1378) to 16.4% (9/55) and from 12.1% (4773/39542) to 2.4% (118/5004), respectively. In WNH pediatric patients, the difference in the percentage of all LTx made up by CF patients between the two eras was 41.2% compared to NW patients where the difference was 11%. Similarly in adults, the difference between the two eras was 10.4% in WNH and 2.4% in NW patients.

CONCLUSIONS: The recent reduction in LTx for the CF population has had less impact on the NW population in the US, so the continuation of optimal referrals for this group is needed.

PMID:36206358 | DOI:10.1111/petr.14404

PLoS One. 2022 Oct 7;17(10):e0275256. doi: 10.1371/journal.pone.0275256. eCollection 2022.

ABSTRACT

OBJECTIVES: Here we used whole genome sequencing (WGS) to understand strain diversity and potential for patient-to-patient transmission of Staphylococcus aureus among children with cystic fibrosis (CF) in Queensland, Australia.

METHODS: S. aureus isolates (n = 401) collected between January 2018 and April 2019 from 184 patients with CF (n = 318 isolates) and 76 patients without CF (n = 83 isolates) were subjected to WGS and subsequent multilocus sequence typing (MLST), and a phylogeny was constructed from core genome single nucleotide polymorphism (SNP) analysis. The subsequent data was compared with available patient information.

RESULTS: WGS revealed that patients with CF were essentially colonised by the same genotypes as those seen in patients without CF. Sequence types (ST) for our patients with CF were predominantly ST5 (20.1%), ST30 (7.3%), ST15 (6.3%) and ST8 (5.3%). Two Australian clones, ST93 and ST239, typically seen in skin infections and health-care settings, respectively, were notably absent from our patients with CF. Based on a SNP distance threshold of 14 SNPs, 20 cluster types involving 50/260 patients were evident; of these, 6 clusters contained only patients found to be siblings or otherwise living in the same household. Epidemiological relationships could not be determined for a remaining 14 cluster types involving 38 patients, comprising 2-7 (median 2) patients each. Multiple S. aureus genotypes were observed in 19/73 CF patients who provided more than one sample.

CONCLUSION: These results show that WGS is a useful tool for surveillance of S. aureus strains in children with CF and that the strains in our CF cohort were largely consistent with those circulating in patients without CF. Overall, this confirms previous findings and indicates that S. aureus acquisition in children with CF is similar to that of other patient groups, with limited evidence of potential patient-to-patient transmission within this patient group.

PMID:36206247 | DOI:10.1371/journal.pone.0275256