Staphylococcus aureus in the airways of cystic fibrosis patients - A retrospective long-term study

Schwerdt, Mathias; Neumann, Claudia; Bianca, Schwartbeck; Kampmeier, Stefanie; Herzog, Susann; Görlich, Dennis; Dübbers, Angelika; Große-Onnebrink, Jörg; Keßler, Christina; Kühnl, P.; Schültingkemper, Holger; Janina, Treffon; Peters, Georg; Kahl, Barbara C.

doi:10.1016/j.ijmm.2018.02.003

Cited by 45 publications

(55 citation statements)

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“…Due to strong infiltration by PMNs (Konstan et al, 1994) and an imbalance of the redox system (Ziady & Hansen, 2014), the CF airways represent an oxidative stressful and challenging environment for invading pathogens like S. aureus. Nevertheless, this bacterium is able to persist in this niche for up to several years (Kahl et al, 1998;Schwerdt et al, 2018), which demonstrates its impressive adaptive capacity. To combat oxidative stress, S. aureus possesses two metal-F I G U R E 7 Fold changes in gene expression of sodA (a) and sodM (b) in bacteria internalised for 1 and 2 hr in CFBE41o − cells compared with gene expression in extracellular bacteria, which were in contact with epithelial cells, analysed by RT-qPCR.…”

Section: Discussionmentioning

confidence: 99%

“…Staphylococcus aureus is the most common and one of the first pathogens that can be isolated from the airways of CF patients (Cystic Fibrosis Foundation Patient Registry, ). Despite antistaphylococcal treatment, S. aureus is able to persist over several years (Kahl et al, ; Schwerdt et al, ), causing inflammation (Sagel et al, ) and a decline in lung function (Junge et al, ). The long‐term persistence of S. aureus might be facilitated by its ability to enter, replicate, and reside in professional phagocytes like macrophages (Li et al, ) and neutrophils (Gresham et al, ) and non‐professional phagocytes as keratinocytes, fibroblasts, endothelial, and epithelial cells (Strobel et al, ), including also CF cells (Jarry & Cheung, ; Kahl et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Importance of superoxide dismutases A and M for protection ofStaphylococcus aureusin the oxidative stressful environment of cystic fibrosis airways

Janina

Chaves‐Moreno

Niemann

et al. 2020

Cellular Microbiology

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Staphylococcus aureus is one of the earliest pathogens that persists the airways of cystic fibrosis (CF) patients and contributes to increased inflammation and decreased lung function. In contrast to other staphylococci, S. aureus possesses two superoxide dismutases (SODs), SodA and SodM, with SodM being unique to S. aureus. Both SODs arm S. aureus for its fight against oxidative stress, a by‐product of inflammatory reactions. Despite complex investigations, it is still unclear if both enzymes are crucial for the special pathogenicity of S. aureus. To investigate the role of both SODs during staphylococcal persistence in CF airways, we analysed survival and gene expression of S. aureus CF isolates and laboratory strains in different CF‐related in vitro and ex vivo settings. Bacteria located in inflammatory and oxidised CF sputum transcribed high levels of sodA and sodM. Especially expression values of sodM were remarkably higher in CF sputum than in bacterial in vitro cultures. Interestingly, also S. aureus located in airway epithelial cells expressed elevated transcript numbers of both SODs, indicating that S. aureus is exposed to oxidative stress at various sites within CF airways. Both enzymes promoted survival of S. aureus during polymorphonuclear leukocyte killing and seem to act compensatory, thereby giving evidence that the interwoven interaction of SodA and SodM contributes to S. aureus virulence and facilitates S. aureus persistence within CF airways.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Importance of superoxide dismutases A and M for protection ofStaphylococcus aureusin the oxidative stressful environment of cystic fibrosis airways

Janina

Chaves‐Moreno

Niemann

et al. 2020

Cellular Microbiology

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“…This trend is concerning as MRSA been independently associated with decreased lung function and increased mortality among CF patients (Dasenbrook et al, 2008(Dasenbrook et al, , 2010. S. aureus is also one of the earliest colonizers of the CF airway, and acquired strains can persist for years, often dominated by a single intrahost lineage (Al-Zubeidi et al, 2014;Kahl et al, 2003;Schwerdt et al, 2018). However, trajectories of S. aureus carriage vary by patient (Kahl et al, 2013;Schwerdt et al, 2018), reflecting the complexities of patient-specific CF management and complicating our understanding of pathogen adaptation.…”

Section: Discussionmentioning

confidence: 99%

“…A key component of CF patient treatment is management of bacterial respiratory pathogens, including Staphylococcus aureus, which may colonize the CF lung for years (Branger et al, 1996). This often requires recurrent and prolonged periods of antimicrobial use (Schwerdt et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…However, in comparison to Pseudomonas aeruginosa (Feliziani et al, 2014;Marvig et al, 2015) or even Burkholderia spp. (Lieberman et al, 2011a(Lieberman et al, , 2014Price et al, 2013;Silva et al, 2016), less is known about S. aureus intrahost evolution in the CF lung (Ankrum and Hall, 2017;McAdam et al, 2011;Rolain et al, 2009;Schwerdt et al, 2018). The various species inhabiting the CF lung share several evolutionary strategies relating to persistent microbial carriage.…”

Section: Introductionmentioning

confidence: 99%

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Long-term intrahost evolution of methicillin resistant Staphylococcus aureus among cystic fibrosis patients with respiratory carriage

Azarian

Ridgway

Zhen

et al. 2019

Preprint

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Staphylococcus aureus is the most commonly identified airway colonizer of cystic fibrosis (CF) patients, and infections with methicillin-resistant S. aureus (MRSA) are associated with poor outcomes. Yet, little is known about the intrahost evolution of S. aureus among CF patients. We investigated convergent evolution and adaptation of MRSA among four CF patients with longterm respiratory carriage. For each patient, we performed whole-genome sequencing on an average of 21 isolates (range: 19-23) carried for a mean of 1,403 days (range: 903-1,679), including 25 pairs of isolates collected on the same day. We then assessed intrahost diversity, population structure, evolutionary history, and signatures of adaptation in the context of patient age, antibiotic treatment, and co-colonizing microbes. We conducted tests of gene-wide diversifying selection and identified instances of switched intergenic regions (IGRs), which may be associated with gene expression. Phylogenetic analysis delineated distinct multilocus sequence type ST5 (n=3) and ST72 (n=1) clonal populations in addition to sporadic, non-clonal isolates, and uncovered a putative transmission event. Variation in antibiotic resistance was observed within clonal populations, even among isolates collected on the same day. Coalescent analysis revealed rates of molecular evolution ranging from 2.21 to 8.64 nucleotide polymorphisms per genome per year. Estimated lineage ages were consistent with acquisition of colonization in early childhood and subsequent persistence of multiple sub-populations. Selection analysis focused on 1,622 core genes shared by all four clonal populations (n=79). Eleven genes were variable in three subjects -most notable, ATP-dependent protease clpX, 2-oxoglutarate dehydrogenase odhA, fmtC, and transcription-repair coupling factor mfd. Only one gene, staphylococcal protein A (spa), was found to have evidence of gene-wide diversifying selection. We identified three instances of intrahost IGR switching events, two of which flanked genes related to quorum sensing. The ecology of microbes in the airways of CF patients is undeniably complex, posing challenges for management. We illustrate appreciable intrahost diversity as well as persistence of a dominant lineage. We also show that intrahost adaptation is a continual process, despite purifying selective pressure, and provide targets that should be investigated further for their function in CF adaptation. Contribution to the FieldStaphylococcus aureus is the most commonly identified airway colonizer of cystic fibrosis (CF) patients, and infections with methicillin-resistant S. aureus (MRSA) are associated with poor outcomes. Yet, little is known about the intrahost evolution of S. aureus among CF patients. We investigated convergent evolution and adaptation of MRSA among four CF patients with longterm respiratory carriage. We found that each patient possessed a single predominant strain in addition to transient non-clonal isolates. Considerable genomic diversity was observed among intrahost popula...

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Association between early chronic methicillin‐susceptible Staphylococcus aureus colonization and lung function in children with cystic fibrosis

Sunman

Yalçın

Özsezen

et al. 2022

Pediatric Pulmonology

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Background: Our aim was to determine whether early chronic methicillin-susceptible Staphylococcus aureus (MSSA) colonization in children with cystic fibrosis (CF) is associated at 8 years of age with poorer lung function, poorer nutritional status, and increased exacerbation frequency. Methods: In this retrospective cohort study, a total of 52 children with chronic MSSA colonization were included. Of them, 26 were chronically colonized with MSSA before the age of 4 years (early onset), and 26 were chronically colonized from 4 years to 6 years of age (late-onset). At the age of 8 years, lung function, body mass index (BMI) as an indicator of nutritional status and frequency of pulmonary exacerbations were compared between two groups.Results: At 8 years of age, BMI was similar between the early-onset and late-onset groups (15.

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Staphylococcus aureus in the airways of cystic fibrosis patients - A retrospective long-term study

Cited by 45 publications

References 27 publications

Importance of superoxide dismutases A and M for protection ofStaphylococcus aureusin the oxidative stressful environment of cystic fibrosis airways

Importance of superoxide dismutases A and M for protection ofStaphylococcus aureusin the oxidative stressful environment of cystic fibrosis airways

Long-term intrahost evolution of methicillin resistant Staphylococcus aureus among cystic fibrosis patients with respiratory carriage

Association between early chronic methicillin‐susceptible Staphylococcus aureus colonization and lung function in children with cystic fibrosis

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