Antibiotic Molecules: Intracellular

Intracellular antibiotic molecules are the essential components of innate, that is nonadaptive, immunity. Some of these, such as the iron-binding molecules lactoferrin and neutrophil gelatinase-associated lipocalin, deprive microorganisms of the essential nutrient iron by binding iron directly or by binding siderophores that bacteria use for their iron uptake. These molecules inhibit bacterial growth but do not kill bacteria. This is in contrast to the antibiotic peptides that have a broad antibacterial spectrum such as the -defensins HNP1-3 and the human cathelicidin antimicrobial peptide hCAP-18. In general, these are small peptides that have a surplus of positively charged amino acids and hydrophobic amino acids. They bind to microorganisms by virtue of their positive charge and make lytic holes in the bacteria by inserting themselves into the surface membrane. Other antibiotic molecules are short-lived molecular reagents such as nitrous oxide and hypochlorous acid that are generated by specific activation of phagocytes, the cells equipped especially for microbicidal activity.

Key Concepts:

  • Iron deprivation is an important strategy for inhibiting growth of microorganisms.
  • Antibiotic peptides are positively charged molecules that bind to the negatively charged surface of microorganisms and make holes in their membrane.
  • Reactive oxygen derivatives such as superoxide anions and hypochlorous acid are generated by phagocytes and kill microorganisms.

Keywords: antibiotic peptides; Nramp; lactoferrin; vitamin B12-binding protein; phospholipase A2; reactive oxygen derivatives

Figure 1. A neutrophil phagocytises microorganisms and takes them into a phagocytic vacuole (inset, Figure 2) into which the two major granule subsets empty their contents to create a microbicidal milieu.
Figure 2. Inset from Figure 1 showing how major bactericidal systems are generated when contents of peroxidase-positive and peroxidase-negative granules meet in the phagocytic vacuole. MPO works on hydrogen peroxide, the end product of the NADPH oxidase from specific granule membranes. Proteinase 3 from peroxidase-positive granules activates the cathelicidin hCAP18 from specific granules.
Figure 3. The function of the NADPH oxidase as a combined electron and proton transporter.
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Borregaard, Niels, and Sørensen, Ole Erik(Jun 2010) Antibiotic Molecules: Intracellular. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000495.pub3]