AUTHOR=Brown-Jaque Maryury , Rodriguez Oyarzun Lirain , Cornejo-Sánchez Thais , Martín-Gómez Maria T. , Gartner Silvia , de Gracia Javier , Rovira Sandra , Alvarez Antonio , Jofre Joan , González-López Juan J. , Muniesa Maite 

TITLE=Detection of Bacteriophage Particles Containing Antibiotic Resistance Genes in the Sputum of Cystic Fibrosis Patients

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.00856

DOI=10.3389/fmicb.2018.00856

ISSN=1664-302X

ABSTRACT=<p>Cystic fibrosis (CF) is a chronic disease in which the bacterial colonization of the lung is linked to an excessive inflammatory response that leads to respiratory failure. The microbiology of CF is complex. <italic>Staphylococcus aureus</italic> is the first bacterium to colonize the lungs in 30% of pediatric CF patients, and 80% of adult patients develop a chronic <italic>Pseudomonas aeruginosa</italic> infection, but other microorganisms can also be found. The use of antibiotics is essential to treat the disease, but antibiotic performance is compromised by resistance mechanisms. Among various mechanisms of transfer of antibiotic resistance genes (ARGs), the recently been reported bacteriophages are the least explored in clinical settings. To determine the role of phages in CF as mobile genetic elements (MGEs) carrying ARGs, we evaluated their presence in 71 CF patients. 71 sputum samples taken from these patients were screened for eight ARGs (<italic>bla</italic><sub>TEM</sub>, <italic>bla</italic><sub>CTX-M-1</sub>-group, <italic>bla</italic><sub>CTX-M-9</sub>-group, <italic>bla</italic><sub>OXA-48</sub>, <italic>bla</italic><sub>VIM</sub>, <italic>mecA</italic>, <italic>qnrA</italic>, and <italic>qnrS</italic>) in the bacteriophage DNA fraction. The phages found were also purified and observed by electron microscopy. 32.4% of CF patients harbored ARGs in phage DNA. β-lactamase genes, particularly <italic>bla</italic><sub>VIM</sub> and <italic>bla</italic><sub>TEM</sub>, were the most prevalent and abundant, whereas <italic>mecA</italic>, <italic>qnrA</italic>, and <italic>qnrS</italic> were very rare. <italic>Siphoviridae</italic> phage particles capable of infecting <italic>P. aeruginosa</italic> and <italic>Klebsiella pneumoniae</italic> were detected in CF sputum. Phage particles harboring ARGs were found to be abundant in the lungs of both CF patients and healthy individuals and could contribute to the colonization of multiresistant strains.</p>