Dataset Information

Staphylococcus aureus small-colony variants are independently associated with worse lung disease in children with cystic fibrosis.

ABSTRACT:

Background

Cystic fibrosis (CF) lung disease is associated with diverse bacteria chronically infecting the airways. Slow-growing, antibiotic-resistant mutants of Staphylococcus aureus known as small-colony variants (SCVs) have been isolated from respiratory secretions from European adults and children with CF lung disease using specific but infrequently used culture techniques. Staphylococcus aureus SCVs can be selected either by exposure to specific antibiotics or by growth with another CF pathogen, Pseudomonas aeruginosa. We sought to determine the prevalence, clinical significance, and likely mechanisms of selection of S. aureus SCVs among a US cohort of children with CF.

Methods

We performed a 2-year study of 100 children with CF using culture techniques sensitive for S. aureus SCVs, and evaluated associations with clinical characteristics using multivariable regression models.

Results

Staphylococcus aureus SCV infection was detected among 24% of participants and was significantly associated with a greater drop in lung function during the study (P = .007, adjusted for age and lung function at enrollment). This association persisted after adjusting for infection with other known CF pathogens, including P. aeruginosa and methicillin-resistant S. aureus. Evidence indicated that S. aureus SCVs were likely selected in vivo by treatment with the antibiotic trimethoprim-sulfamethoxazole and possibly by coinfection with P. aeruginosa.

Conclusions

Infection with SCV S. aureus was independently associated with worse CF respiratory outcomes in this pediatric cohort. As many clinical microbiology laboratories do not specifically detect S. aureus SCVs, validation and extension of these findings would require widespread changes in the usual laboratory and clinical approaches to these bacteria.

SUBMITTER: Wolter DJ

PROVIDER: S-EPMC3888146 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Publications

Staphylococcus aureus small-colony variants are independently associated with worse lung disease in children with cystic fibrosis.

Wolter Daniel J DJ Emerson Julia C JC McNamara Sharon S Buccat Anne M AM Qin Xuan X Cochrane Elizabeth E Houston Laura S LS Rogers Geraint B GB Marsh Peter P Prehar Karandeep K Pope Christopher E CE Blackledge Marcella M Déziel Eric E Bruce Kenneth D KD Ramsey Bonnie W BW Gibson Ronald L RL Burns Jane L JL Hoffman Lucas R LR

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20130426 3

<h4>Background</h4>Cystic fibrosis (CF) lung disease is associated with diverse bacteria chronically infecting the airways. Slow-growing, antibiotic-resistant mutants of Staphylococcus aureus known as small-colony variants (SCVs) have been isolated from respiratory secretions from European adults and children with CF lung disease using specific but infrequently used culture techniques. Staphylococcus aureus SCVs can be selected either by exposure to specific antibiotics or by growth with another ...[more]

PMID: 23625938

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Project description:Laboratory models have been invaluable for the field of microbiology for over 100?years and have provided key insights into core aspects of bacterial physiology such as regulation and metabolism. However, it is important to identify the extent to which these models recapitulate bacterial physiology within a human infection environment. Here, we performed transcriptomics (RNA-seq), focusing on the physiology of the prominent pathogen Staphylococcus aureus in situ in human cystic fibrosis (CF) infection. Through principal-component and hierarchal clustering analyses, we found remarkable conservation in S. aureus gene expression in the CF lung despite differences in the patient clinic, clinical status, age, and therapeutic regimen. We used a machine learning approach to identify an S. aureus transcriptomic signature of 32 genes that can reliably distinguish between S. aureus transcriptomes in the CF lung and in vitro The majority of these genes were involved in virulence and metabolism and were used to improve a common CF infection model. Collectively, these results advance our knowledge of S. aureus physiology during human CF lung infection and demonstrate how in vitro models can be improved to better capture bacterial physiology in infection.IMPORTANCE Although bacteria have been studied in infection for over 100?years, the majority of these studies have utilized laboratory and animal models that often have unknown relevance to the human infections they are meant to represent. A primary challenge has been to assess bacterial physiology in the human host. To address this challenge, we performed transcriptomics of S. aureus during human cystic fibrosis (CF) lung infection. Using a machine learning framework, we defined a "human CF lung transcriptome signature" that primarily included genes involved in metabolism and virulence. In addition, we were able to apply our findings to improve an in vitro model of CF infection. Understanding bacterial gene expression within human infection is a critical step toward the development of improved laboratory models and new therapeutics.

Dataset Information

Staphylococcus aureus small-colony variants are independently associated with worse lung disease in children with cystic fibrosis.

Background

Methods

Results

Conclusions

Publications

Staphylococcus aureus small-colony variants are independently associated with worse lung disease in children with cystic fibrosis.

Similar Datasets

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