The Impact of Dietary Transition Metals on Host-Bacterial Interactions

Abstract

Transition metals are required cofactors for many proteins that are critical for life, and their concentration within cells is carefully maintained to avoid both deficiency and toxicity. To defend against bacterial pathogens, vertebrate immune proteins sequester metals, in particular zinc, iron, and manganese, as a strategy to limit bacterial acquisition of these necessary nutrients in a process termed "nutritional immunity." In response, bacteria have evolved elegant strategies to access metals and counteract this host defense. In mammals, metal abundance can drastically shift due to changes in dietary intake or absorption from the intestinal tract, disrupting the balance between host and pathogen in the fight for metals and altering susceptibility to disease. This review describes the current understanding of how dietary metals modulate host-microbe interactions and the subsequent impact on the outcome of disease.

Boiling Acid Mimics Intracellular Giant Virus Genome Release

“…However, at and below pH 3, ~60% of the SMBV capsids had opened. While the conditions that produced an increase in SMBV POP (pH ≤ 3) are more acidic than the environment predicted within the amoebal phagosome (Flannagan et al, 2015;German et al, 2013;Lopez and Skaar, 2018), they are similar. Thus, it demonstrates that our in vitro results reflect a relevant stage of the GV infection mechanism.…”

“…Redox-active proteins are also thought to play an important role in protecting the viruses from the harsh conditions present in the host phagosome. During phagocytosis amoebal phagosomes drop to ~pH 4 (not low enough to trigger stargate opening), but they are also inundated with metals (like Cu and Zn) and reactive oxygen species (German et al, 2013;Lopez and Skaar, 2018). Both viruses release metalbinding proteins (identified by d in Table 1) including SMBV's lanosterol demethylase (AHJ40393.1) --a cytochrome p450-like protein--and prolyl 4-hydroxylase (AMK61959.1) and TV's mg709 (AUL77661.1) --a putative prolyl 4-hydroxylase with iron ion binding capabilities--and Cu-Zn superoxide dismutase (AUL78503.1).…”

Enterococcus faecalismanganese exporter MntE alleviates manganese toxicity and is required for mouse gastrointestinal colonization

“…Manganese (Mn) is an essential metal for most bacteria and serves as a cofactor for proteins involved in metabolism, DNA replication, respiration, and oxidative stress (1). Accordingly, Mn acquisition contributes to bacterial virulence in multiple bacterial species (2-4). In order to limit bacterial growth and virulence, the host sequesters Mn as a defense response termed nutritional immunity (1, 4-6).…”

“…Accordingly, Mn acquisition contributes to bacterial virulence in multiple bacterial species (2-4). In order to limit bacterial growth and virulence, the host sequesters Mn as a defense response termed nutritional immunity (1, 4-6). To counteract these host-mediated defences, many bacterial pathogens including Enterococci encode dedicated systems to acquire Mn.…”

Think zinc: Role of zinc poisoning in the intraphagosomal killing of bacteria by the amoeba Dictyostelium

“…Upon phagocytosis, the innate immune phagocyte restricts intravacuolar bacterial growth either by depleting essential metal ions (e.g. Fe 2+ and Mn 2+ ) or by accumulating others, such as Cu 2+ and Zn 2+ , to intoxicating concentrations [reviewed in (Flannagan et al, 2015; Lopez and Skaar, 2018)]. On the pathogen side, bacteria have evolved several strategies to survive excess of metal ions, both in the environment (Ducret et al, 2016; Gonzalez et al, 2018) and in contact with phagocytes (Botella et al, 2011).…”