Intracellular Antibiotic Molecules

Abstract

Phagocytes kill microbes through the action of intracellularly molecules that can be released into the phagolysosome or to the extracellular milieu. In particular, neutrophils have a vast arsenal of peptides and proteins with antimicrobial activity of importance for killing of ingested microbes. Many of these (poly)peptides act through membrane permeabilisation and subsequent lysis of bacteria, while others kill by depriving microbes of important nutrients such as iron. Furthermore, phagocytes generate short‐lived low‐molecular intermediates such as oxygen radicals and nitric oxide of great importance for the ability to kill ingested microbes. Microbes have developed elaborate strategies to circumvent exposure to intracellular antibiotic molecules by blocking cellular activation or blocking granule fusion with the phagolysosome.

Key Concepts

  • Phagocytes kill microbes through the action of intracellular antibiotic molecules.
  • Antibiotic (poly)peptides are positively charged molecules that bind to the negatively charged surface of microorganisms and kill bacteria through lysis.
  • Other antibiotic molecules limit bacterial growth by iron deprivation or through enzymatic activity.
  • Reactive oxygen derivatives such as superoxide anions and hypochlorous acid are generated by phagocytes and kill microorganisms.
  • Microbes have developed several strategies to circumvent killing of intracellular antibiotic molecules.

Keywords: antibiotic peptides; Nramp; lactoferrin; phospholipase A2; reactive oxygen derivatives, NADPH oxidase

Figure 1. Schematic drawing of a neutrophil that phagocytises microorganisms and takes them into a phagocytic vacuole (framed) where the two major granule subsets empty their content to create a microbicidal milieu.
Figure 2. Insert from Figure showing how major bactericidal systems are generated by combining the contents of peroxidase‐positive and peroxidase‐negative granules. MPO works on the hydrogen peroxide end product of the NADPH oxidase from specific granule membranes. Elastase from peroxidase‐positive granules activates the cathelicidin hCAP‐18 from specific granules.
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Sørensen, Ole E(Aug 2015) Intracellular Antibiotic Molecules. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000495.pub4]