Mechanisms of action of microbicides commonly used in infection prevention and control

Abstract

SUMMARYUnderstanding how commonly used chemical microbicides affect pathogenic microorganisms is important for formulation of microbicides. This review focuses on the mechanism(s) of action of chemical microbicides commonly used in infection prevention and control. Contrary to the typical site-specific mode of action of antibiotics, microbicides often act via multiple targets, causing rapid and irreversible damage to microbes. In the case of viruses, the envelope or protein capsid is usually the primary structural target, resulting in loss of envelope integrity or denaturation of proteins in the capsid, causing loss of the receptor-binding domain for host cell receptors, and/or breakdown of other viral proteins or nucleic acids. However, for certain virucidal microbicides, the nucleic acid may be a significant site of action. The region of primary damage to the protein or nucleic acid is site-specific and may vary with the virus type. Due to their greater complexity and metabolism, bacteria and fungi offer more targets. The rapid and irreversible damage to microbes may result from solubilization of lipid components and denaturation of enzymes involved in the transport of nutrients. Formulation of microbicidal actives that attack multiple sites on microbes, or control of the pH, addition of preservatives or potentiators, and so on, can increase the spectrum of action against pathogens and reduce both the concentrations and times needed to achieve microbicidal activity against the target pathogens.

Keywords: bacteria; formulated microbicides; mechanism of action; microbicidal actives; virus.

Fig 1

Classes of active ingredients used in United States EPA-registered microbicidal formulations intended for (A) households or (B) industrial and institutional use [data from reference (7)].

Fig 2

Hierarchy of susceptibility of pathogens to microbicidal active ingredients. Certain formulated microbicides may include combinations of active ingredients, resulting in synergistic virucidal efficacy greater than that displayed by the individual active ingredients [data are from reference (12)].

Fig 3

The rapid effect of the QAC/bacterial cell membrane interaction results in disruption of the bacterial membrane and inactivation upon contact. Blue spheres represent positively charged nitrogen atoms [based on reference (31)].

Fig 4

Inactivation versus time (log₁₀ reduction equivalents) studies for ADBAC (top panel) and DDAC (bottom panel) versus 2 × 10⁹ CFU/mL S. aureus at 25°C (—) and 35°C (----) in a HEPES buffer medium. Final challenge concentrations studied were 35 µg/mL (▲ and Δ), 45 µg/mL (■ and □), and 55 µg/mL (● and ○), and each symbol indicates the mean ± standard error (SE) for five observations [data are from reference (30)].

Fig 5

The rapid effect of the QAC/viral envelope interaction results in disruption of the lipid envelope (analogous to the microbial membrane) and inactivation upon contact [adapted from reference (37) with permission of American Chemical Society].

Fig 6

Ultrastructural changes in S. aureus NCIMB 9518 following 5 min exposure to an alcohol hand rub, as observed using transmission electron microscopy. Cell wall damage (WD) leading to leakage of intracellular material (L) is evident, as shown by arrows; UEM, unidentified extracellular material; scale bar, 157 nm [reprinted from reference (40), with permission of the publisher (copyright Elsevier)].