Michael Strong

National Jewish Health · Center for Genes, Environment, and Health

Lung disease caused by nontuberculous mycobacteria (NTM) is an emerging infectious disease of global significance. Epidemiologic studies have shown the Hawaiian Islands have the highest prevalence of NTM lung infections in the United States. However, potential environmental reservoirs and species diversity have not been characterized. In this cross...

Genome sequencing of Mycobacterium abscessus strains that infect the lungs suggests a possible shift in the bacterium's mode of infection from environmental acquisition to human transmission. This finding has clinical implications.

Amid the ongoing COVID-19 pandemic, it has become increasingly important to monitor the mutations that arise in the SARS-CoV-2 virus, to prepare public health strategies and guide the further development of vaccines and therapeutics. The spike (S) protein and the proteins comprising the RNA-Dependent RNA Polymerase (RdRP) are key vaccine and drug t...

Mycobacterium avium complex (MAC) species constitute most mycobacteria infections in persons with cystic fibrosis (CF) in the United States, but little is known about their genomic diversity or transmission. During 2016–2020, we performed whole-genome sequencing on 364 MAC isolates from 186 persons with CF from 42 cystic fibrosis care centers (CFCC...

RationaleMycobacterium abscessus is a significant threat to individuals with cystic fibrosis (CF) due to innate drug resistance and potential transmission between patients. Recent studies described global dominant circulating clones of M. abscessus, but detailed genomic surveys have not yet been described for the United States (US). Objectives We e...

As environmental opportunistic pathogens, nontuberculous mycobacteria (NTM) can cause severe and difficult to treat pulmonary disease. In the United States, Hawai’i has the highest prevalence of infection. Rapid growing mycobacteria (RGM) such as Mycobacterium abscessus and M. porcinum and the slow growing mycobacteria (SGM) including M. intracellu...

To address the ongoing global tuberculosis crisis, there is a need for shorter, more effective treatments. A major reason why tuberculosis requires prolonged treatment is that, following a short initial phase of rapid killing, the residual Mycobacterium tuberculosis withstands drug killing. Because existing methods lack sensitivity to quantify low-...

Nontuberculous mycobacteria (NTM) are ubiquitous environmental opportunistic pathogens that can cause chronic lung disease. Within the United States, Hawai’i has the highest incidence of NTM lung disease, though the precise reasons are yet to be fully elucidated. One possibility is the high prevalence of NTM in the Hawai’i environment acting as a p...

Rationale The prevalence of nontuberculous mycobacterial (NTM) pulmonary disease varies geographically in the United States. Previous studies indicate that the presence of certain water-quality constituents in source water increases NTM infection risk. Objective To identify water-quality constituents that influence the risk of NTM pulmonary infect...

Rationale: Outbreaks of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) have been reported at CF Centers with conflicting conclusions. Occurrence of NTM at the University of Vermont Medical Center Adult CF Program was investigated. Objectives: Utilize the Healthcare-associated Links in Transmission of NTM (HALT NTM) to...

Two mycobacteriophages were administered intravenously to a male with treatment-refractory Mycobacterium abscessus pulmonary infection and severe cystic fibrosis lung disease. The phages were engineered to enhance their capacity to lyse M. abscessus and were selected specifically as the most effective against the subject’s bacterial isolate. In the...

Nontuberculous mycobacteria (NTM) are opportunistic pathogens that cause chronic pulmonary disease (PD). NTM infections are thought to be acquired from the environment; however, the basal environmental factors that drive and sustain NTM prevalence are not well understood. The highest prevalence of NTM PD cases in the United States is reported from...

Rationale Nontuberculous mycobacteria (NTM) are ubiquitous environmental bacteria that may cause chronic lung disease and are one of the most difficult-to-treat infections among persons with cystic fibrosis (pwCF). Environmental factors likely contribute to increased NTM densities, with higher potential for exposure and infection. Objective To ide...

Rationale: Healthcare-associated transmission of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) has been investigated at CF Centers worldwide, with conflicting conclusions. We investigated transmission at the Colorado Adult CF Program. Objectives: To systematically investigate healthcare-associated transmission and/or...

Motivation Short-read whole genome sequencing (WGS) is a vital tool for clinical applications and basic research. Genetic divergence from the reference genome, repetitive sequences, and sequencing bias reduce the performance of variant calling using short-read alignment, but the loss in recall and specificity has not been adequately characterized....

Background Healthcare-associated transmission of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) has been reported and is of increasing concern. No standardized epidemiologic investigation tool has been published for healthcare-associated NTM outbreak investigations. This report describes the design of an ongoing observat...

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Whole genome sequencing (WGS) has recently been used to investigate acquisition of Mycobacterium abscessus (MABC). Investigators have reached conflicting conclusions about the meaning of genetic distances for interpretation of person-to-person transmission. Existing genomic studies were limited by a lack of WGS from environmental MABC isolates. In...

Mycobacterium abscessus, a multidrug-resistant nontuberculous mycobacterium, has emerged as a major pathogen affecting people with cystic fibrosis (CF). Although originally thought to be acquired independently from the environment, most individuals are infected with one of several dominant circulating clones (DCCs), indicating the presence of globa...

Recent studies have characterized a dominant clone (Clone 1) of Mycobacterium abscessus subspecies massiliense ( M. massiliense ) associated with high prevalence in cystic fibrosis (CF) patients, pulmonary outbreaks in the United States (US) and United Kingdom (UK), and a Brazilian epidemic of skin infections. The prevalence of Clone 1 in non-CF pa...

Whole-genome sequencing (WGS) has shown immense value in enabling identification and characterization of bacterial taxa. This is particularly true for mycobacteria, where culture-based characterization becomes delayed by the inherently slow growth rate of these organisms. This chapter reviews the general techniques behind WGS and their optimization...

Building upon the foundational research of Robert Koch, who demonstrated the ability to grow Mycobacterium tuberculosis for the first time in 1882 using media made of coagulated bovine serum, microbiologists have continued to develop new and more efficient ways to grow mycobacteria. Presently, all known mycobacterial species can be grown in the lab...

Background Viruses, including bacteriophages, are important components of environmental and human associated microbial communities. Viruses can act as extracellular reservoirs of bacterial genes, can mediate microbiome dynamics, and can influence the virulence of clinical pathogens. Various targeted metagenomic analysis techniques detect viral sequ...

Mycobacterium abscessus is a rapidly growing nontuberculous mycobacterial species that comprises three subspecies; M. abscessus subsp . abscessus, M. abscessus subsp . massiliense, and M. abscessus subsp . bolletii . These predominantly environmental microorganisms have emerged as life-threatening chronic pulmonary pathogens in both immunocompetent...

Background: Short-read whole genome sequencing (WGS) is a vital tool for clinical applications and basic research. Genetic divergence from the reference genome, repetitive sequences, and sequencing bias, reduce the performance of variant calling using short-read alignment, but the loss in recall and specificity has not been adequately characterized...

Although uncommon, nontuberculous mycobacterial (NTM) pulmonary infection in the Hawaiian Islands has a relatively high incidence and mortality compared to the mainland U.S. As a result, this study examines the possible geological and hydrological pathways by which NTM patients may become infected, including the environmental conditions that may fa...

Amid the ongoing COVID-19 pandemic, it has become increasingly important to monitor the mutations that arise in the SARS-CoV-2 virus, to prepare public health strategies and guide the further development of vaccines and therapeutics. The spike (S) protein and the proteins comprising the RNA-Dependent RNA Polymerase (RdRP) are key vaccine and drug t...

Background: Viruses, including bacteriophage, are important components of environmental and human associated microbial communities. Viruses can act as extracellular reservoirs of bacterial genes, can mediate microbiome dynamics, and can influence the virulence of clinical pathogens. It is essential, therefore, to have robust sequence analysis metho...

With the development of transcriptomic technologies, we are able to quantify precise changes in gene expression profiles from astronauts and other organisms exposed to spaceflight. Members of NASA GeneLab and GeneLab-associated analysis working groups (AWGs) have developed a consensus pipeline for analyzing short-read RNA-sequencing data from space...

Tuberculosis (TB) is a leading cause of death globally. Understanding the population dynamics of TB's causative agent Mycobacterium tuberculosis complex (Mtbc) in-host is vital for understanding the efficacy of antibiotic treatment. We use longitudinally collected clinical Mtbc isolates that underwent Whole-Genome Sequencing from the sputa of 200 p...

Nontuberculous mycobacteria (NTM) are environmental organisms that can cause opportunistic pulmonary disease with species diversity showing significant regional variation. In the United States, Hawai’i shows the highest rate of NTM pulmonary disease. The need for improved understanding of NTM reservoirs led us to identify NTM from patient respirato...

Free-living amoebae are ubiquitous in aquatic environments and act as environmental reservoirs for nontuberculous mycobacteria. Mycobacterium avium subsp. hominissuis recovered from Acanthamoeba has been demonstrated to be more virulent in both human and murine models. Here, we investigate the persistence of M. avium subsp. hominissuis after short-...

Mycobacterium kubicae is 1 of nearly 200 species of nontuberculous mycobacteria (NTM), environmental micro-organisms that in some situations can infect humans and cause severe lung, skin and soft tissue infections. Although numerous studies have investigated the genetic variation among prevalent clinical NTM species, including Mycobacterium abscess...

With the development of transcriptomic technologies, we are able to quantify precise changes in gene expression profiles from astronauts and other organisms exposed to spaceflight. Members of NASA GeneLab and GeneLab-associated analysis working groups (AWGs) have developed a consensus pipeline for analyzing short-read RNA-sequencing data from space...

Globally and in the United States, the prevalence of NTM pulmonary disease—a potentially life-threatening but underdiagnosed chronic illness—is prominently rising. While NTM are ubiquitous in the environment, including in soil, the specific soil components that promote or inhibit NTM growth have not been elucidated. We hypothesized that NTM culture...

Background: Nontuberculous mycobacterial (NTM) infections are increasing in prevalence, with current estimates suggesting that over 100,000 people in the United States are affected each year. It is unclear how certain species of mycobacteria transition from environmental bacteria to clinical pathogens, or what genetic elements influence the differ...

Background: The increasing incidence of drug resistance in tuberculosis and other infectious diseases poses an escalating cause for concern, emphasizing the urgent need to devise robust computational and molecular methods identify drug resistant strains. Although machine learning-based approaches using whole-genome sequence data can facilitate the...

Understanding the physiological processes underlying the ability of Mycobacterium abscessus to become a chronic pathogen of the cystic fibrosis (CF) lung is important to the development of prophylactic and therapeutic strategies to better control and treat pulmonary infections caused by these bacteria. Gene expression profiling of a diversity of M....

Nontuberculous mycobacteria (NTM) are environmental bacteria that may cause chronic lung disease. Environmental factors that favor NTM growth likely increase the risk of NTM exposure within specific environments. We aimed to identify water-quality constituents (Al, As, Cd, Ca, Cu, Fe, Pb, Mg, Mn, Mo, Ni, K, Se, Na, Zn, and pH) associated with NTM d...

Background Nontuberculous mycobacterial (NTM) infections are increasing in prevalence, with current estimates suggesting that over 100,000 people in the United States are affected each year. It is unclear how certain species of mycobacteria transition from environmental bacteria to clinical pathogens, or what genetic elements influence the differen...

Background Nontuberculous mycobacterial (NTM) infections are increasing in prevalence, with current estimates suggesting that over 100,000 people in the United States are affected each year. It is unclear how certain species of mycobacteria transition from environmental bacteria to clinical pathogens, or what genetic elements influence the differen...

We asked young scientists to serve as peer mentors for “Seeking Career Clarity,” the author of the question below. By asking reflective questions, sharing relevant personal experiences, and offering advice, these scientists provide support and perspective.

The rapid development in sequencing technology is creating an increase in demand for largely intact DNA as starting material as very long strands of DNA are sequenced directly to generate reads that are thousands of bases long. Organisms with thick cell walls are difficult to lyse, often impacting both DNA recovery and quality. Consequently, most m...

Comparisons in infectivity among the clinically important nontuberculous mycobacterial (NTM) species have not been explored in great depth. Rapid-growing mycobacteria including Mycobacterium abscessus and Mycobacterium porcinum can cause indolent, but progressive lung disease. Slow-growing members of the Mycobacterium avium complex (MAC) are the mo...

Background Tuberculosis (TB) is a leading cause of death globally from an infectious agent. Understanding the population dynamics of TB’s causative agent Mycobacterium tuberculosis (Mtb) in-host is vital for understanding the efficacy of antibiotic treatment. Here we use longitudinally collected clinical Mtb isolates that underwent Whole-Genome Seq...

Nontuberculous mycobacteria (NTM) pose a threat to individuals with cystic fibrosis (CF) due to an increased prevalence of pulmonary infections, innate drug resistance of the bacteria, and potential transmission between CF patients. To explore the genetic diversity of NTM isolated from CF patients within the United States (US) and to identify poten...

A surgical heater–cooler unit has been implicated as the source for Mycobacterium chimaera infections among cardiac surgery patients in several countries. We isolated M. chimaera from heater–cooler units and patient infections in the United States. Whole-genome sequencing corroborated a risk for these units acting as a reservoir for this pathogen.

Accurate and timely mycobacterial species identification is imperative for successful diagnosis, treatment, and management of disease caused by nontuberculous mycobacteria (NTM). The current most widely utilized method for NTM species identification is Sanger sequencing of one or more genomic loci, followed by BLAST sequence analysis. MALDI-TOF MS...