ABSTRACT
CONTENTS 6.1 Introduction ................................................................................................. 88 6.2 Modes of Action.......................................................................................... 90
6.2.1 General Considerations.................................................................. 90 6.2.2 Cross-Linking=Coagulation........................................................... 91 6.2.3 Oxidation and Oxidizing Agents ................................................. 93 6.2.4 Energy Transfer............................................................................... 95 6.2.5 Other Structure-Disruption Mechanisms.................................... 97
6.3 Modes of Resistance ................................................................................. 100 6.3.1 Introduction ................................................................................... 100 6.3.2 Intrinsic Mechanisms ................................................................... 103
6.3.2.1 Introduction .................................................................... 103 6.3.2.2 Growth Phase Responses ............................................. 104 6.3.2.3 Biofilm Development .................................................... 106 6.3.2.4 Dormancy........................................................................ 108 6.3.2.5 Revival ............................................................................. 111 6.3.2.6 Extreme Mechanism Examples ................................... 112
6.3.3 Acquired Mechanisms ................................................................. 114 6.3.3.1 Introduction .................................................................... 114 6.3.3.2 Mutation .......................................................................... 115 6.3.3.3 Transmissible Elements ................................................ 117
6.4 Conclusions and Perspectives ................................................................ 119 Appendix............................................................................................................. 120 References ........................................................................................................... 120
For the purpose of this chapter, an antimicrobial is considered as any physical or chemical agent that kills or inhibits the growth of microorganisms. These can be further classified as biocides and anti-infectives. Anti-infectives may be described as being rather specific drugs in their interaction and their use for the control of various microorganisms, including antibacterials (with the typical example being antibiotics), antifungals, antivirals, and antiprotozoal agents. Anti-infectives have a rather narrow spectrum of activity, in comparison to most biocides, but have been effective in the treatment of infections due to minimal associated toxicity in humans, animals, and plants, allowing for their systematic use. Examples include antibiotics that demonstrate specific mechanisms of action, narrow ranges of antimicrobial activity, and greater demonstrated risks in the development of bacterial resistance to their action [1]. If antibiotics are considered further, their mechanisms of action have been particularly well studied, and it is known that they specifically target important bacterial processes such as DNA replication (e.g., quinolones) and protein translation (e.g., aminoglycosides, tetracyclines). Their effects on the various types of bacteria can range, but they are generally much narrower than those described for biocides. For example, glycopeptides (e.g., vancomycin) are particularly effective against gram-positive bacteria (with the notable exception of mycobacteria), isoniazid is specifically antimycobacterial, and the macrolides and aminoglycosides are active against most gram-positive and gram-negative bacteria [1]. These limitations in the range of activity are linked to the presence of (or access to) specific targets in these bacteria, which are simply not found in other microorganisms or host cells. Therefore, the majority of antibiotics have no therapeutic uses against viruses and fungi. Others, especially specific antifungal agents such as the azoles and polyenes, target ergosterol synthesis and structure; ergosterol is a specific sterolic molecule found in fungal cell membranes [1]. Further, antiviral drugs such as amantadine inhibit viral (specifically influenza virus) penetration into host cells [2]. Their mechanisms of action [1,2] and resistance [1-3] have been particularly well described elsewhere and are not considered further in this chapter. In contrast, biocides are chemical or indeed physical agents that are used on inanimate surfaces or on the skin and mucous membranes. These antimicrobials are much more widely employed for various applications including preservation, sanitization, pasteurization, fumigation, antisepsis, disinfection, and sterilization. As these terms can vary in definition and use, some standardized definitions are provided in the Appendix for reference. These broad-spectrum chemical agents include chlorine, phenols, heavy metals, and quaternary ammonium compounds (QACs). Physical agents include heat and radiation. They demonstrate a wider range of antimicrobial activity but also have associated cellular toxicity, which has therefore limited their use to surface=air applications,
and Related
with only a limited number being used on the skin, mucous membranes, or in wounds (e.g., iodophors, triclosan, and chlorhexidine (CHG)) [4]. The mechanisms of action of biocides are often difficult to study and determine as they have been shown to have multiple targets on surface components and interior structures in microorganisms [5,6]. Despite this, their principal modes of action may be considered under four general mechanisms including cross-linking or coagulation, oxidation, energy transfer, and other structure-disrupting agents (Table 6.1).
