Population Genomics and Inference of Mycobacterium avium Complex Clusters in Cystic Fibrosis Care Centers, United States

Abstract

N ontuberculous mycobacteria (NTM) are ubiquitous microorganisms found in indoor and outdoor habitats, including water, soil, and dust. NTM can infect susceptible persons, including those with lung diseases such as cystic fi brosis (CF) (1). Previous surveys conducted in the United States have found that Mycobacterium avium complex (MAC) species are clinically relevant and the most frequently isolated NTM (2). MAC consists of 9 slow-growing mycobacterial species (3-6), of which the 2 most frequently observed are M. avium (MAV) and M. intracellulare, including its subspecies intracellulare (MINT) and subspecies chimaera (MCHIM) (4). In the United States, most persons with CF and positive NTM cultures (61%) had MAC species infections (2,7). MAC infections increased by 3% annually during 2010-2014.MAC pulmonary infections are probably acquired by inhalation of aerosols ( 8), but the sources and modes of transmission of MAC remain unclear. Studies using various molecular genotyping methods have shown MAC isolates from human airway samples to have high genetic similarity to isolates from animals (8-10), water (11,12), bathroom faucets (13), showerheads (14,15), pools (16), and soil (17). Other potential MAC infection sources include fomites, zoonotic sources, and contaminated materials (10,18). Despite the clinical relevance of MAC and its prevalence among persons with CF, the genomic relationships of MAC isolates and the potential for person-to-person transmission are poorly understood. Whole-genome sequencing (WGS) to analyze the genetic diversity of MAC is aimed at identifying MAC infections that cluster by high bacterial genomic sequence similarity, particularly in susceptible populations such as persons with CF. Unclustered isolates are unrelated and are therefore not implicated in transmission, but clustering between MAC isolates suggests that they are derived from the same source (i.e., shared water, surfaces, or person-to-person transmission). To this end, we analyzed the WGS of NTM isolates

Host and pathogen response to bacteriophage engineered against Mycobacterium abscessus lung infection

“…Whole genome sequencing (WGS) libraries were prepared with the NexteraXT Library Prep Kit (Illumina Inc., San Diego, CA), and library sizes were assessed on an Agilent BioAnalyzer (Agilent Technologies, Santa Clara, CA). Multiplexed library pools were sequenced on the Illumina MiSeq (2X300bp paired end reads) as described (Davidson et al, 2021a;Hasan et al, 2021). Single Nucleotide Polymorphisms (SNPs) were analyzed using a read mapping approach with bowtie2 (Langmead and Salzberg, 2012) and SAMtools mpileup (Li et al, 2009) as described previously (Davidson et al, 2021a).…”

Healthcare-associated links in transmission of nontuberculous mycobacteria among people with cystic fibrosis (HALT NTM) study: Rationale and study design

“…Clusters are defined as highly similar strains at the genomic level, harbored by two or more pwCF who are cared for at the same CF Care Center. We are using the CO-NRC WGS data to identify clusters and inform CF Care Centers of NTM clusters at their Center [ 27 , 28 ]. National Jewish Health Intuitional Review Board initially approved this study (#HS-3175-528) on October 9, 2018 and renewed approval on October 4, 2019.…”

Nontuberculous Mycobacterial Lung Disease in the Patients with Cystic Fibrosis—A Challenging Diagnostic Problem

“…Recent molecular epidemiologic investigations (whole genome sequencing g-WGS) indicate that health-care related transmission of M. abscessus is rare [ 22 , 23 ]. Nevertheless, Hassan et al found that 15% of clustering of MAC isolates concerned patients sharing CF centers, thus indicating a common source of infection [ 24 ].…”