Characteristics of the copper‐induced viable‐but‐non‐culturable state in bacteria

Abstract

The antimicrobial applications of copper (Cu) are exploited in several industries, such as agriculture and healthcare settings. While Cu is capable of efficiently killing microorganisms, sub-lethal doses can induce a viable-but-non-culturable (VBNC) state in bacteria of many distinct clades. VBNC cells cannot be detected by standard culture-based detection methods, and can become a threat to plants and animals as they often retain virulent traits upon resuscitation. Here we discuss the putative mechanisms of the Cu-induced VBNC state. Common observations in Cu-induced VBNC cells include a cellular response to reactive oxygen species, the exhaustion of energy reserves, and a reconfiguration of the proteome. While showing partial overlap with other VBNC state-inducing stressors, these changes seem to be part of an adaptive response to Cu toxicity. Furthermore, we argue that Cu resistance mechanisms such as P-type ATPases and multicopper oxidases may ward off entry into the VBNC state to some extent. The spread of these mechanisms across multi-species populations could increase population-level resistance to Cu antimicrobials. As Cu resistance mechanisms are often co-selected with antibiotic resistance mechanisms, this threat is exacerbated.

From Copper Tolerance to Resistance in Pseudomonas aeruginosa towards Patho-Adaptation and Hospital Success

“…The transition to the VBNC state is a cell-programmed phenomenon and is not the consequence of sustained cellular damage. It is an active induction of a regulated cellular state, a secondary adaptive response to metal stress [ 77 ].…”

“…The VBNC state shares common features with the quiescent cell state and is defined by a loss of cultivability associated with the maintenance of viability characteristics (intact cell membranes and existence of metabolic activity and gene expression) [ 77 ]. It allows Pa to reorient its metabolism in order to repair the damage suffered and to induce copper tolerance mechanisms by the synthesis of an arsenal of efflux pumps, multi-copper oxidases, storage proteins…[ 78 , 79 ].…”

Current Perspectives on Viable but Non-culturable Bacteria in Food Safety and Public Health

“…Although large-scale studies are yet to determine the comprehensive impacts of different conditions on VBNC induction, several physical and chemical stress factors are suggested to disturb the natural balance of bacterial growth conditions and lead the bacteria to induce the VBNC state (13). Starvation (14), extreme or low temperature (15), osmotic (16) and oxidative stress (17), UV irradiation (18), pulsed light, pulsed electric field (19), heavy metal (20), and acute alteration of pH or salinity (21), as well as food processing and preservation strategies (22), are the main uncovered factors stressing the bacteria to VBNC state as shown in Figure 1.…”

Nanomaterials-Upconverted Hydroxyapatite for Bone Tissue Engineering and a Platform for Drug Delivery

“…Cu can destroy bacteria through lipid peroxidation, oxidation of protein, DNA disruption and promoting reactive oxygen species (ROS). 69 Essentially, the antibacterial activities of copper are known to be more efficient in high temperatures and high relative humidity within hours. 31 , 34 In one study viable endospores in Clostridium difficile spp.…”