Manganese in Pathogens

[percyval577]

A manganese-rich enviroment supports superoxide dismutase activity in a Lyme disease pathogen, Borrelia Burgdorferi
Aguirre et al 2013


Discussion, 2nd and 3rd paragraph

The accumulation of unusually high manganese in B. burgdorferi that we report here has not been previously documented, although our values are very similar to those published by Ouyang et al. (21). In studies by Posey and Gherardini (15), the manganese in B. burgdorferi cell lysates was reported to be only 2–3-fold higher than that of E. coli and might reflect differential growth conditions used because our cells were grown to near stationary phase. In any case, our findings clearly demonstrate a tremendous capacity for manganese uptake without toxicity in this spirochete. In fact, in our preliminary studies comparing manganese across various species (not shown), the levels of the metal in whole cell B. burgdorferi are comparable with Lactobacillus plantarum, notoriously known for hyperaccumulating manganese without a SOD enzyme (42).

First, in the absence of iron-requiring enzymes, manganese may be more widely used as a co-factor. Consistent with this, we observe a close association with B. burgdorferi manganese and an aminopeptidase (Fig. 2A), a metalloenzyme that employs iron in other organisms (35). Moreover, the ability of B. burgdorferi to accumulate high manganese may represent yet another fascinating adaptation of the organism to the metal starvation response of innate immunity. When infected, the host not only systemically starves pathogens of iron (16, 17), but macrophages and neutrophils attempt to limit manganese bioavailability for the invading species (43–45). High manganese is essential for virulence in B. burgdorferi (21), and SodA may only be part of the story.

From the Results, 5th paragraph

In the course of these metal analyses, we noted the spirochete accumulates unusually high levels of manganese. As seen in Fig. 3A, B. burgdorferi accumulated 2 orders of magnitude higher levels of manganese per cell than E. coli grown in BSK medium in parallel. This high level of manganese was seen with both the ML23 and the 297 strain backgrounds and by metal analysis with both AAS and ICP-MS (Fig. 3, A and C). Because cell volumes for the spirochete are difficult to estimate, we normalized manganese on the basis of soluble cellular protein and compared values in B. burgdorferi, E. coli, and the eukaryote, bakers' yeast. Yeast and E. coli are reported to accumulate similar micromolar concentrations of manganese (10, 11), and we also find similar manganese levels in these organisms when analyzed per mg of protein (Fig. 3B). By comparison, the level of manganese that accumulated in B. burgdorferi was 2 orders of magnitude higher (Fig. 3B).

open access
J Biol Chem. 2013 Mar 22;288(12):8468-78. doi: 10.1074/jbc.M112.433540. Epub 2013 Feb 2.​

 

[percyval577]

They measured the following amounts, at the y-axis in A, B and C upper diagram it´s not linear scales.
B shows Mn content per protein weight, A per cells, and upper C as well, including a Mn- transporter-mutant.

FIGURE 3.


The above mentioned Ouyang et al 2009 compare Mn content in wildtype (strain 297) with mutants [diagram B],
and give [in diagram C] the Zn content, which is still higher but only roughly 4 times (I don´t know normal or usual ratios, I had a short glance, but in vain so far).

 

[percyval577]

I guess high manganese serves candida albicans:

Candida albicans expresses an unusual cytoplasmic manganese-containing superoxide dismutase (SOD3 gene product) upon the entry and during the stationary phase
Lamarre et al 2001


abstract, my prgrphs

We report here that in addition to a cytoplasmic copper-zinc-containing superoxide dismutase (SOD) and a mitochondrial manganese-containing SOD,

Candida albicans expresses a third SOD gene (SOD3). The deduced amino acid sequence contains all of the motifs found in previously characterized manganese-containing SODs, except the presence of a mitochondrial transit peptide. Recombinant Sod3p expressed and purified from Escherichia coli is a homotetramer with a subunit mass of 25.4 kDa. Mass absorption spectrometry detected the presence of both iron and manganese in purified Sod3p but, as determined by metal replacement experiments,

the enzyme displays activity only when bound to manganese. Overexpression of SOD3 was shown to rescue the hypersensitivity to redox cycling agents of a Saccharomyces cerevisiae mutant lacking the cytoplasmic copper-zinc-containing SOD.

Northern blot analyses showed that the transcription of SOD3 is induced neither by the transition from the yeast to the mycelial form of C. albicans nor by drug-induced oxidative stress. In continuous cultures, the expression of SOD3 was strongly stimulated upon the entry and during the stationary phase, concomitantly with the repression of SOD1. We conclude that Sod3p is an atypical cytosolic manganese-containing superoxide dismutase that is involved in the protection of C. albicans against reactive oxygen species during the stationary phase.

open access​

Candida albicans adapts to host copper during infection by swapping metal cofactors for superoxide dismuase
Li et al 2015


abstract, my prgrphs

Copper is both an essential nutrient and potentially toxic metal, and during infection the host can exploit Cu in the control of pathogen growth. Here we describe a clever adaptation to Cu taken by the human fungal pathogen Candida albicans. In laboratory cultures with abundant Cu, C. albicans expresses a Cu-requiring form of superoxide dismutase (Sod1) in the cytosol;

but when Cu levels decline, cells switch to an alternative Mn-requiring Sod3. This toggling between Cu- and Mn-SODs is controlled by the Cu-sensing regulator Mac1 and ensures that C. albicans maintains constant SOD activity for cytosolic antioxidant protection despite fluctuating Cu.

This response to Cu is initiated during C. albicans invasion of the host where the yeast is exposed to wide variations in Cu. In a murine model of disseminated candidiasis, serum Cu was seen to progressively rise over the course of infection, but this heightened Cu response was not mirrored in host tissue.

The kidney that serves as the major site of fungal infection showed an initial rise in Cu, followed by a decline in the metal. C. albicans adjusted its cytosolic SODs accordingly and expressed Cu-Sod1 at early stages of infection,

followed by induction of Mn-Sod3 and increases in expression of CTR1 for Cu uptake. Together, these studies demonstrate that fungal infection triggers marked fluctuations in host Cu and C. albicans readily adapts by modulating Cu uptake and by exchanging metal cofactors for antioxidant SODs.

open access​

 

[percyval577]

As it looks that SARS COV 2 can trigger a post illness syndrome that might match ME criteria, the following might be of interest for this thread. Finding fits though all coronoviruses.

The Severe Acute Respiratory Syndrome Coronavirus Nsp15 Protein is an Endoribonuclease that preferes Manganese as a Cofactor

Bhardwaj et al

abstract

Nonstructural protein 15 (Nsp15) of the severe acute respiratory syndrome coronavirus (SARS-CoV) produced in Escherichia coli has endoribonuclease activity that preferentially cleaved 5′ of uridylates of RNAs. Blocking either the 5′ or 3′ terminus did not affect cleavage. Double- and single-stranded RNAs were both substrates for Nsp15 but with different kinetics for cleavage. Mn2+ at 2 to 10 mM was needed for optimal endoribonuclease activity, but Mg2+ and several other divalent metals were capable of supporting only a low level of activity.

Concentrations of Mn2+ needed for endoribonuclease activity induced significant conformation change(s) in the protein, as measured by changes in tryptophan fluorescence. A similar endoribonucleolytic activity was detected for the orthologous protein from another coronavirus, demonstrating that the endoribonuclease activity of Nsp15 may be common to coronaviruses. This work presents an initial biochemical characterization of a novel coronavirus endoribonuclease.

open access​