Cystic Fibrosis Rapid Response: Translating Multi-omics Data into Clinically Relevant Information.

Ana Georgina Cobián Güemes,Rob Edwards,Robert A Quinn,Rohaum Hamidi,Sean Benler,Yan Wei Lim,Daniel Cuevas,Forest Rohwer,Vito Adrian Cantú,Heather Maughan,Thomas Brettin,Pieter Dorrestein,Douglas J Conrad,Vanessa Sperandio

doi:10.1128/mbio.00431-19

Ana Georgina Cobián Güemes, Rob Edwards + Show 12 more

Open Access

https://doi.org/10.1128/mbio.00431-19

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Abstract

Pulmonary exacerbations are the leading cause of death in cystic fibrosis (CF) patients. To track microbial dynamics during acute exacerbations, a CF rapid response (CFRR) strategy was developed. The CFRR relies on viromics, metagenomics, metatranscriptomics, and metabolomics data to rapidly monitor active members of the viral and microbial community during acute CF exacerbations. To highlight CFRR, a case study of a CF patient is presented, in which an abrupt decline in lung function characterized a fatal exacerbation. The microbial community in the patient's lungs was closely monitored through the multi-omics strategy, which led to the identification of pathogenic shigatoxigenic Escherichia coli (STEC) expressing Shiga toxin. This case study illustrates the potential for the CFRR to deconstruct complicated disease dynamics and provide clinicians with alternative treatments to improve the outcomes of pulmonary exacerbations and expand the life spans of individuals with CF.IMPORTANCE Proper management of polymicrobial infections in patients with cystic fibrosis (CF) has extended their life span. Information about the composition and dynamics of each patient's microbial community aids in the selection of appropriate treatment of pulmonary exacerbations. We propose the cystic fibrosis rapid response (CFRR) as a fast approach to determine viral and microbial community composition and activity during CF pulmonary exacerbations. The CFRR potential is illustrated with a case study in which a cystic fibrosis fatal exacerbation was characterized by the presence of shigatoxigenic Escherichia coli The incorporation of the CFRR within the CF clinic could increase the life span and quality of life of CF patients.

Highlights

Pulmonary exacerbations are the leading cause of death in cystic fibrosis (CF) patients
Microbial community dynamics in CF lungs follow the climax attack model (CAM) [11, 12], in which a climax community is acclimated to the host and dominates during stable periods and a transient attack community is associated with exacerbations
In the CAM, attack communities lead to cystic fibrosis pulmonary exacerbations (CFPEs), declines in lung function, and eventually death

Summary

Introduction

Pulmonary exacerbations are the leading cause of death in cystic fibrosis (CF) patients. To highlight CFRR, a case study of a CF patient is presented, in which an abrupt decline in lung function characterized a fatal exacerbation. This case study illustrates the potential for the CFRR to deconstruct complicated disease dynamics and provide clinicians with alternative treatments to improve the outcomes of pulmonary exacerbations and expand the life spans of individuals with CF. IMPORTANCE Proper management of polymicrobial infections in patients with cystic fibrosis (CF) has extended their life span. We propose the cystic fibrosis rapid response (CFRR) as a fast approach to determine viral and microbial community composition and activity during CF pulmonary exacerbations. Antibiotic treatments and proper disease management have extended the average life span of CF patients; these polymicrobial lung infections are still the primary cause of morbid-. In the CAM, attack communities lead to cystic fibrosis pulmonary exacerbations (CFPEs), declines in lung function, and eventually death. Preventing CFPE relies on quickly identifying attack viral and microbial communities and the genes that they carry and express, such as those encoding specific toxins [13], to efficiently tailor antimicrobial therapies

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