Cystic fibrosis lung microbiome: Opportunities to reconsider management of airway infection

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113756/1/ppul23243.pd

Comparative genomics of Mycobacterium avium complex reveals signatures of environment-specific adaptation and community acquisition

Nontuberculous mycobacteria, including those in the Mycobacterium avium complex (MAC), constitute an increasingly urgent threat to global public health. Ubiquitous in soil and water worldwide, MAC members cause a diverse array of infections in humans and animals that are often multidrug resistant, intractable, and deadly. MAC lung disease is of particular concern and is now more prevalent than tuberculosis in many countries, including the United States. Although the clinical importance of these microorganisms continues to expand, our understanding of their genomic diversity is limited, hampering basic and translational studies alike. Here, we leveraged a unique collection of genomes to characterize MAC population structure, gene content, and within-host strain dynamics in unprecedented detail. We found that different MAC species encode distinct suites of biomedically relevant genes, including antibiotic resistance genes and virulence factors, which may influence their distinct clinical manifestations. We observed that M. avium isolates from different sources-human pulmonary infections, human disseminated infections, animals, and natural environments-are readily distinguished by their core and accessory genomes, by their patterns of horizontal gene transfer, and by numerous specific genes, including virulence factors. We identified highly similar MAC strains from distinct patients within and across two geographically distinct clinical cohorts, providing important insights into the reservoirs which seed community acquisition. We also discovered a novel MAC genomospecies in one of these cohorts. Collectively, our results provide key genomic context for these emerging pathogens and will facilitate future exploration of MAC ecology, evolution, and pathogenesis

Challenging scenarios in nontuberculous mycobacterial infection in cystic fibrosis

This review summarizes the discussion of a session held during the 2018 North American Cystic Fibrosis (CF) Conference titled “Challenging Cases in Nontuberculous Mycobacterial (NTM) Management.” In this session, a multidisciplinary panel of NTM experts discussed clinical challenges related to the management of NTM infection in people with CF in which decision‐making falls outside of the Cystic Fibrosis Foundation/European Cystic Fibrosis Society NTM guidelines. Topics discussed included managing newly acquired NTM infection, selecting and monitoring treatment regimens, determining treatment endpoints, and caring for patients after NTM treatment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153589/1/ppul24604_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153589/2/ppul24604.pd

Differences in alpha diversity between lysis protocols.

<p>Samples processed with the modified protocol had higher levels of (A) richness (p = 0.04, paired t-test), and higher (C) Shannon diversity (p = 0.004, paired t-test) than samples processed with the standard protocol. (B) Evenness did not differ between the lysis protocols (p = 0.06, paired t-test). Blue and red symbols represent paired samples with greater separation on NMDS. Error bars indicate mean and SD.</p

Characteristics of NTM culture-positive samples.

<p>Characteristics of NTM culture-positive samples.</p

Improvement in NTM DNA extraction from spiked sputum samples with the modified as compared to the standard lysis protocol.

<p>Log₁₀ <i>atpE</i> gene copies/mL in DNA extracted from sputum spiked with either (A) MABSC or (B) MAC using the standard (blue circles) or the modified (red squares) lysis protocols. Error bars indicate mean and SD.</p

Impact of lysis method on community structure.

<p>Bray-Curtis-based nonmetric multidimensional scaling (NMDS) plot showing pairwise comparison of samples processed with the standard (blue symbols) or modified (red symbols) lysis protocols. Solid symbols represent paired samples with greater separation.</p

Culture-Independent Identification of Nontuberculous Mycobacteria in Cystic Fibrosis Respiratory Samples - Fig 2

<p>(A) Relative abundances of NTM OTUs and (B) total bacterial load in NTM culture-positive samples. (A) The mean relative abundance of NTM OTUs in the samples processed with the standard protocol was not significantly different from that observed when these samples were processed with the modified protocol (mean 0.098% and 1.21%, respectively; p = 0.08, paired t-test). (B) Total bacterial load in NTM culture-positive samples as measured by 16S rRNA gene qPCR did not significantly differ between lysis protocols. (p = 0.91, paired t-test). Error bars indicate mean and SD.</p