Nontuberculous Mycobacteria Show Differential Infectivity and Use Phospholipids to Antagonize LL-37.
Honda. Jennifer R JR; Hess. Tamara T; Carlson. Rachel R; Kandasamy. Pitchaimani P; Nieto Ramirez. Luisa Maria LM; Norton. Grant J GJ; Virdi. Ravleen R; Islam. M Nurul MN; Mehaffy. Carolina C; Hasan. Nabeeh A NA; Epperson. L Elaine LE; Hesser. Danny D; Alper. Scott S; Strong. Michael M; Flores. Sonia C SC; Voelker. Dennis R DR; Dobos. Karen M KM; Chan. Edward D ED
Key Findings
- Infectivity of NTM species and even individual isolates varies widely in human macrophages.
- Some NTM strains are more virulent and harder for immune cells to clear.
- Modified phospholipids, possibly phosphatidylinositol or cardiolipin, can block the antibacterial action of LL‑37.
Practical Outcomes
- For those experimenting with immune‑boosting approaches (e.g., LL‑37 supplementation), be aware that certain bacterial lipids can neutralize its effect, so infection status matters. This insight doesn’t change any specific dosing or protocol yet, but it highlights the need to consider bacterial composition when targeting innate immunity.
Summary
The study shows that different types of non‑TB mycobacteria infect immune cells to varying degrees, and some of them can protect themselves from the natural antibacterial peptide LL‑37 by using special fats in their cell walls.
Abstract
Comparisons of infectivity among the clinically important nontuberculous mycobacteria (NTM) species have not been explored in great depth. Rapid-growing mycobacteria, including <i>Mycobacterium abscessus</i> and <i>M. porcinum</i>, can cause indolent but progressive lung disease. Slow-growing members of the <i>M. avium</i> complex are the most common group of NTM to cause lung disease, and molecular approaches can now distinguish between several distinct species of <i>M. avium</i> complex including <i>M. intracellulare</i>, <i>M. avium</i>, <i>M. marseillense</i>, and <i>M. chimaera</i>. Differential infectivity among these NTM species may, in part, account for differences in clinical outcomes and response to treatment; thus, knowing the relative infectivity of particular isolates could increase prognostication accuracy and enhance personalized treatment. Using human macrophages, we investigated the infectivity and virulence of nine NTM species, as well as multiple isolates of the same species. We also assessed their capacity to evade killing by the antibacterial peptide cathelicidin (LL-37). We discovered that the ability of different NTM species to infect macrophages varied among the species and among isolates of the same species. Our biochemical assays implicate modified phospholipids, which may include a phosphatidylinositol or cardiolipin backbone, as candidate antagonists of LL-37 antibacterial activity. The high variation in infectivity and virulence of NTM strains suggests that more detailed microbiological and biochemical characterizations are necessary to increase our knowledge of NTM pathogenesis.
Study Information
pubmed
2020
10.1165/rcmb.2018-0278oc