Host Response to Nontuberculous Mycobacterial Infections of Current Clinical Importance

Abstract

The nontuberculous mycobacteria are a large group of acid-fast bacteria that are very widely distributed in the environment. While Mycobacterium avium was once regarded as innocuous, its high frequency as a cause of disseminated disease in HIV-positive individuals illustrated its potential as a pathogen. Much more recently, there is growing evidence that the incidence of M. avium and related nontuberculous species is increasing in immunocompetent individuals. The same has been observed for M. abscessus infections, which are very difficult to treat; accordingly, this review focuses primarily on these two important pathogens. Like the host response to M. tuberculosis infections, the host response to these infections is of the TH1 type but there are some subtle and as-yet-unexplained differences.A lthough nontuberculous mycobacteria have long been recognized, there is far less information regarding their pathogenicity than that of their more famous relatives Mycobacterium tuberculosis and Mycobacterium leprae. It is becoming increasingly clear, however, that the incidence of certain members of the nontuberculous mycobacterial family may be increasing, an observation not related simply to better recognition, typing, and diagnosis. Of this family, the host response to M. avium is perhaps the best understood, but even here there are interesting differences in the expression of immunity that have yet to be explained. NOMENCLATUREOne cannot begin to address this issue without considering the current nomenclature, a morass in itself. We are using here the term "nontuberculous mycobacteria" (NTM) but could easily use "atypical mycobacteria," "environmental mycobacteria," the subset "rapidly growing mycobacteria" (RGM), "mycobacteria other than M. tuberculosis," or even the "quasi-too-complex" term that can be applied to M. avium and M. abscessus. NTM is perhaps the most widely used, but one has to realize that "tuberculous" refers to "not tuberculosis" not "no tubercles." ECOLOGY AND EPIDEMIOLOGYNTM were suspected as potential causes of human infections in the sanatorium era, but it was not until the 1950s that direct evidence became available. Even then, NTM were initially regarded as simple saprophytes of limited, if any, virulence occurring only in people with other predisposing lung conditions (as discussed further below). This opinion, of course, changed dramatically when M. avium complex (MAC) species emerged as major opportunistic infections in patients with HIV and more recently with observations of increases in infections with other NTM such as M. abscessus in elderly patients.Because of extensive research, including seminal work by Falkinham, we now know that NTM are widely distributed in the environment and can cause opportunistic infections in multiple mammals, fish, and birds (particularly poultry) (1). In fact, it seems that NTM can grow essentially anywhere (2) and thrive where competing microbes are destroyed, such as in chlorinated water (3). In untreated water, NTM can even parasitize amoebae (4, 5). Eve...

Susceptibility of Mycobacterium abscessus to Antimycobacterial Drugs in Preclinical Models

“…The cure rate for chronic lung and disseminated infections due to NTM is dismal despite prolonged treatment with various multidrug regimens (6,7). Treatment of M. abscessus consists of macrolides, quinolones, amikacin, and other antibiotics.…”

“…RGM cause serious, lifethreatening chronic lung disease and are responsible for disseminated and often fatal infections (6,7). Infections are typically caused by contaminated materials and invasive procedures involving catheters, nonsterile surgical procedures, or injections and implantations of foreign bodies.…”

“…Additional impediments include erythromycin ribosomal methylase (erm) genes found in almost all M. abscessus subsp. abscessus isolates, which result in methylation of the 23S rRNA, rendering the bacteria resistant against macrolides-a mainstay of RGM treatment regimens (6,11,12).…”

“…NTM are ubiquitous in the environment and are responsible for colonization, infection, and pseudo-outbreaks in health care settings throughout the world (5,6). RGM cause serious, lifethreatening chronic lung disease and are responsible for disseminated and often fatal infections (6,7).…”

The Environment of “Mycobacterium avium subsp. hominissuis” Microaggregates Induces Synthesis of Small Proteins Associated with Efficient Infection of Respiratory Epithelial Cells

“…In recent years, there has been a significant increase in the incidence of nontuberculous mycobacterial (NTM) lung infections, including in cystic fibrosis patients, where M. avium subsp. hominissuis accounts for 72% of mycobacterial infections (2)(3)(4). Studies have also found an increase in NTM lung infections in middle-aged women with no known underlying conditions (5).…”