large-scale-sars-cov-2-testing-utilizing-saliva-transposition-sample

Large-Scale SARS-CoV-2 Testing Utilizing Saliva and Transposition Sample Pooling

Identification and isolation of contagious individuals along with quarantine of close contacts, is critical for slowing the spread of COVID-19. ...

Michigan State University

Elexacaftor-Tezacaftor-Ivacaftor (ETI) therapy is showing promising efficacy for treatment of cystic fibrosis (CF) and is becoming more widely available since recent FDA approval. However, little is known about how these drugs will affect lung infections, which are the leading cause of morbidity and mortality among people with CF (pwCF).

A restructuring of microbiome niche space is associated with Elexacaftor-Tezacaftor-Ivacaftor therapy in the cystic fibrosis lung.

Antibiotics are our primary approach to treating complex infections, yet we have a poor understanding of how these drugs affect microbial communities. To better understand antimicrobial effects on host-associated microbial communities we treated cultured sputum microbiomes from people with cystic fibrosis (pwCF, n = 24) with 11 different antibiotics, supported by theoretical and mathematical modeling-based predictions in a mucus-plugged bronchiole microcosm. Treatment outcomes we identified in vitro that were predicted in silico were: 1) community death, 2) community resistance, 3) pathogen killing, and 4) fermenter killing. However, two outcomes that were not predicted when antibiotics were applied were 5) community profile shifts with little change in total bacterial load (TBL), and 6) increases in TBL. The latter outcome was observed in 17.8% of samples with a TBL increase of greater than 20% and 6.8% of samples with an increase greater than 40%, demonstrating significant increases in community carrying capacity in the presence of an antibiotic. An iteration of the mathematical model showed that TBL increase was due to antibiotic-mediated release of pH-dependent inhibition of pathogens by anaerobe fermentation. These dynamics were verified in vitro when killing of fermenters resulted in a higher community carrying capacity compared to a no antibiotic control. Metagenomic sequencing of sputum samples during antibiotic therapy revealed similar dynamics in clinical samples. This study shows that the complex microbial ecology dictates the outcomes of antibiotic therapy against a polymicrobial infection.

Kerri A. Neugebauer

COVID-19 Early Detection Program,
Department of Microbiology and Molecular Genetics,
Department of Plant,
Soil,
and Microbial Sciences,
Department of Plant, Soil, and Microbial Sciences

Michigan State University

Large-Scale SARS-CoV-2 Testing Utilizing Saliva and Transposition Sample Pooling

Kerri A. Neugebauer

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}COVID-19 Early Detection Program,Department of Microbiology and Molecular Genetics,Department of Plant,Soil,and Microbial Sciences,Department of Plant, Soil, and Microbial Sciences

Michigan State University

Large-Scale SARS-CoV-2 Testing Utilizing Saliva and Transposition Sample Pooling

COVID-19 Early Detection Program,
Department of Microbiology and Molecular Genetics,
Department of Plant,
Soil,
and Microbial Sciences,
Department of Plant, Soil, and Microbial Sciences