Evolution of Stenotrophomonas maltophilia in Cystic Fibrosis Lung over Chronic Infection: A Genomic and Phenotypic Population Study.

Alfonso Esposito,Ersilia Fiscarelli,Elisabetta Giacobazzi,Olivier Jousson,Arianna Pompilio,Clotilde Bettua,Giovanni Di Bonaventura,Valentina Crocetta

doi:10.3389/fmicb.2017.01590

Abstract

Stenotrophomonas maltophilia has been recognized as an emerging multi-drug resistant opportunistic pathogen in cystic fibrosis (CF) patients. We report a comparative genomic and phenotypic analysis of 91 S. maltophilia strains from 10 CF patients over a 12-year period. Draft genome analyses included in silico Multi-Locus Sequence Typing (MLST), Single-Nucleotide Polymorphisms (SNPs), and pangenome characterization. Growth rate, biofilm formation, motility, mutation frequency, in vivo virulence, and in vitro antibiotic susceptibility were determined and compared with population structure over time. The population consisted of 20 different sequence types (STs), 11 of which are new ones. Pangenome and SNPs data showed that this population is composed of three major phylogenetic lineages. All patients were colonized by multiple STs, although most of them were found in a single patient and showed persistence over years. Only few phenotypes showed some correlation with population phylogenetic structure. Our results show that S. maltophilia adaptation to CF lung is associated with consistent genotypic and phenotypic heterogeneity. Stenotrophomonas maltophilia infecting multiple hosts likely experiences different selection pressures depending on the host environment. The poor genotype-phenotype correlation suggests the existence of complex regulatory mechanisms that need to be explored in order to better design therapeutic strategies.

Highlights

Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder caused by a mutation targeting the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene
Pseudomonas aeruginosa and Staphylococcus aureus are the most common bacterial pathogens isolated from the CF respiratory tract where they cause persistent infections associated with a more rapid decline in lung function and survival (Emerson et al, 2002)
Ninety-one S. maltophilia strains were isolated over a 12 yearperiod (2003–2014) in sputum samples collected from 10 CF patients at the CF Unit of “Bambino Gesù” Children’s Hospital of Rome, Italy (Table 1)

Summary

Introduction

Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder caused by a mutation targeting the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. This leads to altered regulation of ion transport homeostasis in epithelial cells, in the airways where impaired mucociliary clearance and antimicrobial defense create a perfect niche for microbial colonization. S. maltophilia Evolution in CF Lung led to an increasing number of reports on potentially emerging and challenging pathogens (Parkins and Floto, 2015). In this context, both the overall prevalence and incidence of Stenotrophomonas maltophilia isolations from CF respiratory tract secretions have increased steadily in recent years. The clinical relevance of S. maltophilia remains undetermined because of conflicting results arising from clinical studies focused on the correlation between infection and lung damage (Colin and Rabin, 2011)

Methods

Results

Conclusion