Iron contributes to the antibacterial functions of the haemolymph of Galleria mellonella

Dunphy, Gary B.; Niven, Donald F.; Chadwick, June S.

doi:10.1016/s0022-1910(02)00159-2

Cited by 22 publications

(9 citation statements)

References 34 publications

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“…7). G. mellonella hemolymph contains both iron transport and storage proteins (transferrin and ferritin, respectively), and iron has been shown to be essential to an early antimicrobial response of the insect, where hemocytes limit iron availability to invading pathogens (21). Considering that iron concentration in G. mellonella hemolymph is ca.…”

Section: Discussionmentioning

confidence: 99%

In Vitro and In Vivo Antimicrobial Activities of Gallium Nitrate against Multidrug-Resistant Acinetobacter baumannii

Antunes

Imperi

Minandri

et al. 2012

Antimicrob Agents Chemother

133

144

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b Multidrug-resistant Acinetobacter baumannii poses a tremendous challenge to traditional antibiotic therapy. Due to the crucial role of iron in bacterial physiology and pathogenicity, we investigated iron metabolism as a possible target for anti-A. baumannii chemotherapy using gallium as an iron mimetic. Due to chemical similarity, gallium competes with iron for binding to several redox enzymes, thereby interfering with a number of essential biological reactions. We found that Ga(NO 3 ) 3 , the active component of an FDA-approved drug (Ganite), inhibits the growth of a collection of 58 A. baumannii strains in both chemically defined medium and human serum, at concentrations ranging from 2 to 80 M and from 4 to 64 M, respectively. Ga(NO 3 ) 3 delayed the entry of A. baumannii into the exponential phase and drastically reduced bacterial growth rates. Ga(NO 3 ) 3 activity was strongly dependent on iron availability in the culture medium, though the mechanism of growth inhibition was independent of dysregulation of gene expression controlled by the ferric uptake regulator Fur. Ga(NO 3 ) 3 also protected Galleria mellonella larvae from lethal A. baumannii infection, with survival rates of >75%. At therapeutic concentrations for humans (28 M plasma levels), Ga(NO 3 ) 3 inhibited the growth in human serum of 76% of the multidrug-resistant A. baumannii isolates tested by >90%, raising expectations on the therapeutic potential of gallium for the treatment of A. baumannii bloodstream infections. Ga(NO 3 ) 3 also showed strong synergism with colistin, suggesting that a colistin-gallium combination holds promise as a last-resort therapy for infections caused by pan-resistant A. baumannii.

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Section: Discussionmentioning

confidence: 99%

In Vitro and In Vivo Antimicrobial Activities of Gallium Nitrate against Multidrug-Resistant Acinetobacter baumannii

Antunes

Imperi

Minandri

et al. 2012

Antimicrob Agents Chemother

133

144

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“…The ability of living organisms to sequester free iron is not only necessary for protection against iron toxicity but it is also an innate resistance mechanism of hosts (mammals or insects) to fight infections [45],[46]. Iron incorporated into heme is the most abundant iron source in the mammalian host, being mainly associated with the oxygen-carrying molecule, hemoglobin, sequestered within erythrocytes.…”

Section: Discussionmentioning

confidence: 99%

IlsA, A Unique Surface Protein of Bacillus cereus Required for Iron Acquisition from Heme, Hemoglobin and Ferritin

et al. 2009

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The human opportunistic pathogen Bacillus cereus belongs to the B. cereus group that includes bacteria with a broad host spectrum. The ability of these bacteria to colonize diverse hosts is reliant on the presence of adaptation factors. Previously, an IVET strategy led to the identification of a novel B. cereus protein (IlsA, Iron-regulated leucine rich surface protein), which is specifically expressed in the insect host or under iron restrictive conditions in vitro. Here, we show that IlsA is localized on the surface of B. cereus and hence has the potential to interact with host proteins. We report that B. cereus uses hemoglobin, heme and ferritin, but not transferrin and lactoferrin. In addition, affinity tests revealed that IlsA interacts with both hemoglobin and ferritin. Furthermore, IlsA directly binds heme probably through the NEAT domain. Inactivation of ilsA drastically decreases the ability of B. cereus to grow in the presence of hemoglobin, heme and ferritin, indicating that IlsA is essential for iron acquisition from these iron sources. In addition, the ilsA mutant displays a reduction in growth and virulence in an insect model. Hence, our results indicate that IlsA is a key factor within a new iron acquisition system, playing an important role in the general virulence strategy adapted by B. cereus to colonize susceptible hosts.

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“…Despite the importance of iron availability in insects during infection by bacterial pathogens (Dunphy et al. ; Watson et al. ), the role of this metal during baculovirus infection is poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the importance of iron availability in insects during infection by bacterial pathogens (Dunphy et al 2002;Watson et al 2010), the role of this metal during baculovirus infection is poorly understood. Divalent and trivalent iron cations markedly reduced the pathogenicity of LdMNPV OBs when administered simultaneously with OB inoculum (Shapiro 2001).…”

Section: Discussionmentioning

confidence: 99%

Chemical and biological stress factors on the activation of nucleopolyhedrovirus infections in covertly infected Spodoptera exigua

Virto

Navarro

Tellez

et al. 2016

J Applied Entomology

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Following the consumption of baculovirus occlusion bodies (OBs), insects may succumb to lethal disease, but the survivors can harbour sublethal covert infections and may develop, reproduce and transmit the infection to their offspring. The use of different chemical and biological stressors was examined to determine whether they could be used to activate covert infections in populations of Spodoptera exigua larvae infected by the homologous nucleopolyhedrovirus (SeMNPV). Treatment of covertly infected S. exigua second instars with Tinopal UNPA‐GX, hydroxylamine, paraquat, Bacillus thuringiensis var. kurstaki crystals, spores or mixtures of crystals + spores, or a heterologous nucleopolyhedrovirus (Chrysodeixis chalcites SNPV) did not result in the activation of SeMNPV covert infections. Similarly, virus treatments involving permissive NPVs did not result in greater mortality in covertly infected insects compared with the virus‐free controls. In contrast, 0.1% copper sulphate, 1% iron (II) sulphate and 1 mg/l sodium selenite treatments resulted in 12–41% lethal polyhedrosis disease in covertly infected larvae. A greenhouse trial using copper sulphate and sodium selenite as activation factors applied to covertly infected S. exigua larvae on sweet pepper plants resulted in very low levels of SeMNPV activation (<3%). These results highlight the important roles of copper, iron and selenium in insect immunity and baculovirus‐induced disease. However, these substances seem unlikely to prove useful for the activation of covert SeMNPV infections in S. exigua larvae under greenhouse conditions.

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Iron contributes to the antibacterial functions of the haemolymph of Galleria mellonella

Cited by 22 publications

References 34 publications

In Vitro and In Vivo Antimicrobial Activities of Gallium Nitrate against Multidrug-Resistant Acinetobacter baumannii

In Vitro and In Vivo Antimicrobial Activities of Gallium Nitrate against Multidrug-Resistant Acinetobacter baumannii

IlsA, A Unique Surface Protein of Bacillus cereus Required for Iron Acquisition from Heme, Hemoglobin and Ferritin

Chemical and biological stress factors on the activation of nucleopolyhedrovirus infections in covertly infected Spodoptera exigua

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