The Role of Intermetal Competition and Mis-Metalation in Metal Toxicity

Barwinska-Sendra, Anna; Waldron, Kevin J.

doi:10.1016/bs.ampbs.2017.01.003

Cited by 55 publications

(41 citation statements)

References 229 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because metal concentrations vary significantly throughout microenvironments, bacteria contain dedicated proteins for the import of essential metals and export of excess/toxic metals (Barwinska‐Sendra & Waldron, ). The L. plantarum reference strain WCFS1 contains 42 annotated metal cation transporters (Kleerebezem et al, ).…”

Section: Discussionmentioning

confidence: 99%

Sensitivity to the two peptide bacteriocin plantaricin EF is dependent on CorC, a membrane‐bound, magnesium/cobalt efflux protein

2019

View full text Add to dashboard Cite

Lactic acid bacteria produce a variety of antimicrobial peptides known as bacteriocins. Most bacteriocins are understood to kill sensitive bacteria through receptor‐mediated disruptions. Here, we report on the identification of the Lactobacillus plantarum plantaricin EF (PlnEF) receptor. Spontaneous PlnEF‐resistant mutants of the PlnEF‐indicator strain L. plantarum NCIMB 700965 (LP965) were isolated and confirmed to maintain cellular ATP levels in the presence of PlnEF. Genome comparisons resulted in the identification of a single mutated gene annotated as the membrane‐bound, magnesium/cobalt efflux protein CorC. All isolates contained a valine (V) at position 334 instead of a glycine (G) in a cysteine‐β‐synthase domain at the C‐terminal region of CorC. In silico template‐based modeling of this domain indicated that the mutation resides in a loop between two β‐strands. The relationship between PlnEF, CorC, and metal homeostasis was supported by the finding that PlnEF‐resistance was lost when PlnEF was applied together with high concentrations of Mg2+, Co2+, Zn2+, or Cu2+. Lastly, PlnEF sensitivity was increased upon heterologous expression of LP965 corC but not the G334V CorC mutant in the PlnEF‐resistant strain Lactobacillus casei BL23. These results show that PlnEF kills sensitive bacteria by targeting CorC.

show abstract

Section: Discussionmentioning

confidence: 99%

Sensitivity to the two peptide bacteriocin plantaricin EF is dependent on CorC, a membrane‐bound, magnesium/cobalt efflux protein

2019

View full text Add to dashboard Cite

show abstract

“…Therefore, the toxicity of reactive oxygen species (ROS) is generally thought to be exacerbated by conditions that elevate the intracellular iron pool. Conversely, high levels of intracellular iron may also be toxic independent of ROS, presumably due to the ability of iron to compete with other transition metals, such as manganese, for binding to metal-dependent enzymes or regulators, resulting in mismetallation and inactivation of these proteins 3, 4 . ROS such as H 2 O 2 and superoxide radical can disrupt iron-sulfur clusters and mononuclear iron centers of iron-enzymes, thereby leading to iron release 5, 6 .…”

Section: Introductionmentioning

confidence: 99%

Ferrous iron efflux systems in bacteria

Helmann

2017

Metallomics

View full text Add to dashboard Cite

Bacteria require iron for growth, with only a few reported exceptions. In many environments, iron is a limiting nutrient for growth and high affinity uptake systems play a central role in iron homeostasis. However, iron can also be detrimental to cells when it is present in excess, particularly under aerobic conditions where its participation in Fenton chemistry generates highly reactive hydroxyl radicals. Recent results have revealed a critical role for iron efflux transporters in protecting bacteria from iron intoxication. Systems that efflux iron are widely distributed amongst bacteria and fall into several categories: P1B-type ATPases, cation diffusion facilitator (CDF) proteins, major facilitator superfamily (MFS) proteins, and membrane bound ferritin-like proteins. Here, we review the emerging role of iron export in both iron homeostasis and as part of the adaptive response to oxidative stress.

show abstract

“…Although essential for life, metals can be toxic to bacteria at high concentrations through redox activity, inter-metal competition, and mis-metallation of metalloproteins. 8 Zn is a redox-inactive metal, but can be highly toxic to bacteria through its ability to mis-metallate proteins and liberate redox-active metals, such as copper and iron. 9 In the context of a complex microbial community like the gut microbiota, high gastrointestinal Zn levels likely kill off numerous bacterial species and create a competitive advantage for species that are resistant to metal toxicity.…”

Section: Introductionmentioning

confidence: 99%

The role of zinc and nutritional immunity inClostridium difficileinfection

Zackular

Skaar

2018

Gut Microbes

View full text Add to dashboard Cite

Clostridium difficile in one of the most commonly reported nosocomial pathogens worldwide. Beyond antibiotic use, little is known about the host, microbiota, and environmental factors that contribute to susceptibility to and severity of C. difficile infection (CDI). We recently observed that in a mouse model of CDI, excess dietary zinc (Zn) alters the gut microbiota and decreases resistance to CDI. Moreover, we determined that high levels of Zn exacerbate C. difficile-associated disease and calprotectin-mediated Zn limitation is an essential host response to infection. In this addendum, we discuss how these findings add to our understanding of CDI and consider the potential implications of excess metal intake on the microbiota and infection.

show abstract

The Role of Intermetal Competition and Mis-Metalation in Metal Toxicity

Cited by 55 publications

References 229 publications

Sensitivity to the two peptide bacteriocin plantaricin EF is dependent on CorC, a membrane‐bound, magnesium/cobalt efflux protein

Sensitivity to the two peptide bacteriocin plantaricin EF is dependent on CorC, a membrane‐bound, magnesium/cobalt efflux protein

Ferrous iron efflux systems in bacteria

The role of zinc and nutritional immunity inClostridium difficileinfection

Contact Info

Product

Resources

About