Treatment for chronic methicillin-sensitive<i>Staphylococcus aureus</i>pulmonary infection in people with cystic fibrosis

Ahmed, Molla Imaduddin; Mukherjee, Saptarshi

doi:10.1002/14651858.cd011581.pub2

Cited by 12 publications

(9 citation statements)

References 56 publications

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“…S. aureus underlies diverse clinical diseases, ranging from relatively benign to life-threatening diseases, involving many different organ systems ( 2 – 4 ). Moreover, S. aureus infections, especially noncutaneous infections, are often chronic or relapsing ( 5 – 8 ) and are difficult to eradicate permanently. Despite its medical importance, knowledge of key factors which promote virulence, chronicity, and pathogenicity in S. aureus remains incomplete ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Efficient and Scalable Precision Genome Editing in Staphylococcus aureus through Conditional Recombineering and CRISPR/Cas9-Mediated Counterselection

Penewit

Holmes

McLean

et al. 2018

mBio

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Staphylococcus aureus is an important human pathogen, but studies of the organism have suffered from the lack of a robust tool set for its genetic and genomic manipulation. Here we report the development of a system for the facile and high-throughput genomic engineering of S. aureus using single-stranded DNA (ssDNA) oligonucleotide recombineering coupled with clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated counterselection. We identify recombinase EF2132, derived from Enterococcus faecalis, as being capable of integrating single-stranded DNA oligonucleotides into the S. aureus genome. We found that EF2132 can readily mediate recombineering across multiple characterized strains (3 of 3 tested) and primary clinical isolates (6 of 6 tested), typically yielding thousands of recombinants per transformation. Surprisingly, we also found that some S. aureus strains are naturally recombinogenic at measurable frequencies when oligonucleotides are introduced by electroporation, even without exogenous recombinase expression. We construct a temperature-sensitive, two-vector system which enables conditional recombineering and CRISPR/Cas9-mediated counterselection in S. aureus without permanently introducing exogenous genetic material or unintended genetic lesions. We demonstrate the ability of this system to efficiently and precisely engineer point mutations and large single-gene deletions in the S. aureus genome and to yield highly enriched populations of engineered recombinants even in the absence of an externally selectable phenotype. By virtue of utilizing inexpensive, commercially synthesized synthetic DNA oligonucleotides as substrates for recombineering and counterselection, this system provides a scalable, versatile, precise, inexpensive, and generally useful tool for producing isogenic strains in S. aureus which will enable the high-throughput functional assessment of genome variation and gene function across multiple strain backgrounds.

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Section: Introductionmentioning

confidence: 99%

Efficient and Scalable Precision Genome Editing in Staphylococcus aureus through Conditional Recombineering and CRISPR/Cas9-Mediated Counterselection

Penewit

Holmes

McLean

et al. 2018

mBio

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“…The potential for eradication of newly acquired MRSA infection has recently been demonstrated [ 31 , 32 ], although the clinical sequelae of this has yet to be demonstrated. Unfortunately evidence to support eradication of chronic MRSA infection is currently lacking [ 33 ].…”

Section: Mrsamentioning

confidence: 99%

Staphylococcus aureusin cystic fibrosis: problem bug or an innocent bystander?

Hurley¹

2018

Breathe

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Staphylococcus aureus is a commonly encountered organism in day-to-day living. However, the epidemiology is complicated by three different patterns of carriage. Up to 60% of the population hosts the organism at any one time and, while ∼20% are considered “persistent carriers” due to their status of being continuous hosts of the same strain, a further 20% never host S. aureus and so are considered non-carriers [1]. S. aureus is commonly encountered in childhood with nasopharyngeal carriage among healthy children as high as 48% in the USA [2] and 36% in the Netherlands [3]. S. aureus carriage varies markedly by occupation, as do the proportions of those who carry antibiotic resistant strains (methicillin-resistant S. aureus (MRSA)) [1].

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“…2014 ]. Although methicillin-sensitive S. aureus is an important and common cause of lung infection in CF, there is no agreement on treating long-term infection due to lack of appropriate data [ Ahmed and Mukherjee, 2016 ]. Prophylactic use of flucloxacillin is still routine in some countries, like UK, but is not recommended.…”

Section: Clinical Follow Upmentioning

confidence: 99%

“…Lessons from the cystic fibrosis pig model CF mouse models, developed shortly after the CFTR gene was discovered, lack the characteristic lung disease present in CF patients [Ahmed and Mukherjee, 2016]. To study the origins of CF lung disease, the CF pig, however, proved to be an ideal model [Meyerholz, 2016;Rogers et al 2008].…”

Section: Introductionmentioning

confidence: 99%

Best practices in the treatment of early cystic fibrosis lung disease

Proesmans

2016

Ther Adv Respir Dis

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For many years, management of cystic fibrosis (CF) lung disease was focused on symptomatic treatment of chronic lung infection, which is characterized by cough and sputum production, leading to progressive lung damage. With increasing survival and better knowledge of the pathogenesis of CF lung disease, it has become clear that treatment has to start very early because lung damage occurs in young patients, often before obvious symptoms appear. The arrival of new cystic fibrosis transmembrane conductance-regulator (CFTR)-correcting therapies will bring more opportunities to prevent the disease, apart from only treating chronic lung infection.In this review, a summary of the current knowledge of early CF lung disease is provided, based on animal model studies, as well as on data obtained from well structured follow-up programs after newborn screening (NBS). The most important clinical guidelines for treating young CF patients are also summarized.

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Treatment for chronic methicillin-sensitiveStaphylococcus aureuspulmonary infection in people with cystic fibrosis

Cited by 12 publications

References 56 publications

Efficient and Scalable Precision Genome Editing in Staphylococcus aureus through Conditional Recombineering and CRISPR/Cas9-Mediated Counterselection

Efficient and Scalable Precision Genome Editing in Staphylococcus aureus through Conditional Recombineering and CRISPR/Cas9-Mediated Counterselection

Staphylococcus aureusin cystic fibrosis: problem bug or an innocent bystander?

Best practices in the treatment of early cystic fibrosis lung disease

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