The Staphylococcus aureus Transcriptome during Cystic Fibrosis Lung Infection

Ibberson, Carolyn B.; Whiteley, Marvin

doi:10.1128/mbio.02774-19

Cited by 41 publications

(49 citation statements)

References 57 publications

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“…Recently, two studies have utilized RNA-Seq to examine the transcriptional response of S. aureus in vivo . Work by Ibberson and Whiteley examined the S. aureus transcriptome in the lung of patients with cystic fibrosis (CF) ( 14 ), while Deng et al examined the S. aureus transcriptome during vaginal colonization ( 15 ). The RNA-Seq data sets for these two studies were not yet available at the time that we performed the original search of the GEO database (for our global sRNA expression analysis described above).…”

Section: Resultsmentioning

confidence: 99%

“…In vivo RNA-Seq data sets were acquired from GEO under accession number SRP222773 for CF data and accession number SRP229518 for vaginal data ( 14 , 15 ). For the CF lung data, sRNA expression values (in RPKM) from nine clinical isolate samples were averaged and compared to the averaged sRNA expression values from nine S. aureus cultures grown in chemically defined media (CDM) as well as to those from nine samples from synthetic cystic fibrosis media (SCFM).…”

Section: Methodsmentioning

confidence: 99%

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Reading between the Lines: Utilizing RNA-Seq Data for Global Analysis of sRNAs in Staphylococcus aureus

Sorensen

Keogh

Wittekind

et al. 2020

mSphere

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Regulatory small RNAs (sRNAs) are known to play important roles in the Gram-positive bacterial pathogen Staphylococcus aureus; however, their existence is often overlooked, primarily because sRNA genes are absent from genome annotation files. Consequently, transcriptome sequencing (RNA-Seq)-based experimental approaches, performed using standard genome annotation files as a reference, have likely overlooked data for sRNAs. Previously, we created an updated S. aureus genome annotation file, which included annotations for 303 known sRNAs in USA300. Here, we utilized this updated reference file to reexamine publicly available RNA-Seq data sets in an attempt to recover lost information on sRNA expression, stability, and potential to encode peptides. First, we used transcriptomic data from 22 studies to identify how the expression of 303 sRNAs changed under 64 different experimental conditions. Next, we used RNA-Seq data from an RNA stability assay to identify highly stable/unstable sRNAs. We went on to reanalyze a ribosome profiling (Ribo-seq) data set to identify sRNAs that have the potential to encode peptides and to experimentally confirm the presence of three of these peptides in the USA300 background. Interestingly, one of these sRNAs/peptides, encoded at the tsr37 locus, influences the ability of S. aureus cells to autoaggregate. Finally, we reexamined two recently published in vivo RNA-Seq data sets, from the cystic fibrosis (CF) lung and a murine vaginal colonization study, and identified 29 sRNAs that may play a role in vivo. Collectively, these results can help inform future studies of these important regulatory elements in S. aureus and highlight the need for ongoing curating and updating of genome annotation files. IMPORTANCE Regulatory small RNAs (sRNAs) are a class of RNA molecules that are produced in bacterial cells but that typically do not encode proteins. Instead, they perform a variety of critical functions within the cell as RNA. Most bacterial genomes do not include annotations for sRNA genes, and any type of analysis that is performed using a bacterial genome as a reference will therefore overlook data for sRNAs. In this study, we reexamined hundreds of previously generated S. aureus RNA-Seq data sets and reanalyzed them to generate data for sRNAs. To do so, we utilized an updated S. aureus genome annotation file, previously generated by our group, which contains annotations for 303 sRNAs. The data generated (which were previously discarded) shed new light on sRNAs in S. aureus, most of which are unstudied, and highlight certain sRNAs that are likely to play important roles in the cell.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Reading between the Lines: Utilizing RNA-Seq Data for Global Analysis of sRNAs in Staphylococcus aureus

Sorensen

Keogh

Wittekind

et al. 2020

mSphere

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“…Most significantly, GRIM neutrophils were also found to have reduced bacterial killing capacity, which aligns with the apparent disconnect between NE release and inability to resolve infection in CF airways (89). More recent studies have reported how Staphylococcal superantigen-like protein 13 (SSL13) from Staphylococcus aureus, a common early CF pathogen, can induce neutrophil exocytosis (91) and whose production is evident in the CF microbiome (92). In an age related cohort of non-CF children admitted for acute respiratory distress syndrome (ARDS), neutrophil exocytosis and reduced bacterial killing was observed in individuals co-infected with virus and bacteria but not viral infection alone, suggesting that neutrophil exocytosis may be linked to responses against polymicrobial infection (93).…”

Section: Neutrophil Exocytosismentioning

confidence: 68%

Progress in Model Systems of Cystic Fibrosis Mucosal Inflammation to Understand Aberrant Neutrophil Activity

2020

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In response to recurrent infection in cystic fibrosis (CF), powerful innate immune signals trigger polymorphonuclear neutrophil recruitment into the airway lumen. Exaggerated neutrophil proteolytic activity results in sustained inflammation and scarring of the airways. Consequently, neutrophils and their secretions are reliable clinical biomarkers of lung disease progression. As neutrophils are required to clear infection and yet a direct cause of airway damage, modulating adverse neutrophil activity while preserving their pathogen fighting function remains a key area of CF research. The factors that drive their pathological behavior are still under investigation, especially in early disease when aberrant neutrophil behavior first becomes evident. Here we examine the latest findings of neutrophils in pediatric CF lung disease and proposed mechanisms of their pathogenicity. Highlighted in this review are current and emerging experimental methods for assessing CF mucosal immunity and human neutrophil function in the laboratory.

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“…These strategies, in combination with its fully functional motility, may explain the presence of P. aeruginosa in the deep tissue instead of the wound surface, which is predominantly colonized by S. aureus and S. epidermidis 41 . In a recent study of cystic fibrosis sputum samples, S. aureus was found to be metabolically active in the presence of P. aeruginosa 81 . These results are contrary to the known paradigm that S. aureus is metabolically less active in the presence of P. aeruginosa , forms small colony variants (SCVs), and therefore evades the antibiotics 82 .…”

Section: Cross‐talk In the Quorummentioning

confidence: 99%

Bacterial chatter in chronic wound infections

Buch

Chai

Goluch

2020

Wound Repair Regeneration

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One of the hallmark characteristics of chronic diabetic wounds is the presence of biofilm‐forming bacteria. Bacteria encapsulated in a biofilm may coexist as a polymicrobial community and communicate with each other through a phenomenon termed quorum sensing (QS). Here, we describe the QS circuits of bacterial species commonly found in chronic diabetic wounds. QS relies on diffusion of signaling molecules and the local concentration changes of these molecules that bacteria experience in wounds. These biochemical signaling pathways play a role not only in biofilm formation and virulence but also in wound healing. They are, therefore, key to understanding the distinctive nature of these infections. While several in vivo and in vitro models exist to study QS in wounds, there has been limited progress in understanding the interplay between QS molecules and host factors that contribute to wound healing. Lastly, we examine the potential of targeting QS for both diagnosis and therapeutic intervention purposes.

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The Staphylococcus aureus Transcriptome during Cystic Fibrosis Lung Infection

Cited by 41 publications

References 57 publications

Reading between the Lines: Utilizing RNA-Seq Data for Global Analysis of sRNAs in Staphylococcus aureus

Reading between the Lines: Utilizing RNA-Seq Data for Global Analysis of sRNAs in Staphylococcus aureus

Progress in Model Systems of Cystic Fibrosis Mucosal Inflammation to Understand Aberrant Neutrophil Activity

Bacterial chatter in chronic wound infections

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