scholarly journals Shared and distinct mechanisms of iron acquisition by bacterial and fungal pathogens of humans

Author(s):  
Mélissa Caza ◽  
James W. Kronstad
2012 ◽  
Vol 81 (1) ◽  
pp. 292-302 ◽  
Author(s):  
Guanggan Hu ◽  
Mélissa Caza ◽  
Brigitte Cadieux ◽  
Vivienne Chan ◽  
Victor Liu ◽  
...  

Iron availability is a key regulator of virulence factor elaboration inCryptococcus neoformans, the causative agent of fungal meningoencephalitis in HIV/AIDS patients. In addition, iron is an essential nutrient for pathogen proliferation in mammalian hosts but little is known about the mechanisms of iron sensing and uptake in fungal pathogens that attack humans. In this study, we mutagenizedC. neoformansbyAgrobacterium-mediated T-DNA insertion and screened for mutants with reduced growth on heme as the sole iron source. Among 34 mutants, we identified a subset with insertions in the gene for the ESCRT-I (endosomalsortingcomplexrequired fortransport) protein Vps23 that resulted in a growth defect on heme, presumably due to a defect in uptake via endocytosis or misregulation of iron acquisition from heme. Remarkably,vps23mutants were also defective in the elaboration of the cell-associated capsular polysaccharide that is a major virulence factor, while overexpression ofVps23resulted in cells with a slightly enlarged capsule. These phenotypes were mirrored by a virulence defect in thevps23mutant in a mouse model of cryptococcosis and by hypervirulence of the overexpression strain. Overall, these results reveal an important role for trafficking via ESCRT functions in both heme uptake and capsule formation, and they further reinforce the connection between iron and virulence factor deployment inC. neoformans.


Author(s):  
Sixto M. Leal ◽  
Sanhita Roy ◽  
Chairut Vareechon ◽  
Steven deJesus Carrion ◽  
Heather Clark ◽  
...  

2016 ◽  
Vol 113 (47) ◽  
pp. 13462-13467 ◽  
Author(s):  
Martina Sassone-Corsi ◽  
Phoom Chairatana ◽  
Tengfei Zheng ◽  
Araceli Perez-Lopez ◽  
Robert A. Edwards ◽  
...  

Infections with Gram-negative pathogens pose a serious threat to public health. This scenario is exacerbated by increases in antibiotic resistance and the limited availability of vaccines and therapeutic tools to combat these infections. Here, we report an immunization approach that targets siderophores, which are small molecules exported by enteric Gram-negative pathogens to acquire iron, an essential nutrient, in the host. Because siderophores are nonimmunogenic, we designed and synthesized conjugates of a native siderophore and the immunogenic carrier protein cholera toxin subunit B (CTB). Mice immunized with the CTB–siderophore conjugate developed anti-siderophore antibodies in the gut mucosa, and when mice were infected with the enteric pathogenSalmonella, they exhibited reduced intestinal colonization and reduced systemic dissemination of the pathogen. Moreover, analysis of the gut microbiota revealed that reduction ofSalmonellacolonization in the inflamed gut was accompanied by expansion ofLactobacillusspp., which are beneficial commensal organisms that thrive in similar locales as Enterobacteriaceae. Collectively, our results demonstrate that anti-siderophore antibodies inhibitSalmonellacolonization. Because siderophore-mediated iron acquisition is a virulence trait shared by many bacterial and fungal pathogens, blocking microbial iron acquisition by siderophore-based immunization or other siderophore-targeted approaches may represent a novel strategy to prevent and ameliorate a broad range of infections.


2016 ◽  
Vol 1 (11) ◽  
Author(s):  
Lena Nasser ◽  
Ziva Weissman ◽  
Mariel Pinsky ◽  
Hadar Amartely ◽  
Hay Dvir ◽  
...  

2013 ◽  
Vol 9 (7) ◽  
pp. e1003436 ◽  
Author(s):  
Sixto M. Leal ◽  
Sanhita Roy ◽  
Chairut Vareechon ◽  
Steven deJesus Carrion ◽  
Heather Clark ◽  
...  

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1296
Author(s):  
Felicia Adelina Stanford ◽  
Kerstin Voigt

Iron is a key transition metal required by most microorganisms and is prominently utilised in the transfer of electrons during metabolic reactions. The acquisition of iron is essential and becomes a crucial pathogenic event for opportunistic fungi. Iron is not readily available in the natural environment as it exists in its insoluble ferric form, i.e., in oxides and hydroxides. During infection, the host iron is bound to proteins such as transferrin, ferritin, and haemoglobin. As such, access to iron is one of the major hurdles that fungal pathogens must overcome in an immunocompromised host. Thus, these opportunistic fungi utilise three major iron acquisition systems to overcome this limiting factor for growth and proliferation. To date, numerous iron acquisition pathways have been fully characterised, with key components of these systems having major roles in virulence. Most recently, proteins involved in these pathways have been linked to the development of antifungal resistance. Here, we provide a detailed review of our current knowledge of iron acquisition in opportunistic fungi, and the role iron may have on the development of resistance to antifungals with emphasis on species of the fungal basal lineage order Mucorales, the causative agents of mucormycosis.


Metallomics ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 215-227 ◽  
Author(s):  
Gaurav Bairwa ◽  
Won Hee Jung ◽  
James W. Kronstad

Fungal pathogens of humans acquire iron by high affinity reductive uptake, the use of siderophores, and by heme acquisition. These systems contribute to virulence to different extents in the pathogens.


2017 ◽  
Vol 23 (2) ◽  
Author(s):  
NAVALSINGH J. TODAWAT

Sooty mould diseases of Tress from Aurangabad district were surveyed. During the survey of tress, 5 species were found infected by fungal pathogens causing sooty mould diseases. Disease is easily identifiable by the presence of a black, velvety growth covering the leaf surface area. The fungus produces mycelium which is superficial and dark grows on the flowers, leaf, stem and sometime on fruits also. The severity of disease depends on the honeydew secretions by insects. The diseases were found to be caused by 5 species of fungi viz. Capnodium anonae, C. ramosum, Capnodium sp., Meliola bangalorensis and Meliola ranganthii.


2009 ◽  
Vol 62 ◽  
pp. 402-402
Author(s):  
S.L. Lewthwaite ◽  
P.J. Wright

The predominant diseases of the commercial kumara (Ipomoea batatas) or sweetpotato crop are caused by fungal pathogens The field disease pink rot results from infection by the fungus Sclerotinia sclerotiorum Lesions form on vines but may spread down stems to the roots The widespread nature of this disease in sweetpotato appears peculiar to New Zealand Scurf is a disease caused by Monilochaetes infuscans which occurs in the field but may proliferate amongst stored roots The disease causes a superficial discolouration of the root surface which is mainly cosmetic but can also increase root water loss in storage Infection by Ceratocystis fimbriata produces a disease known as black rot The disease can be transmitted amongst plants at propagation but is particularly rampant amongst roots in storage This disease is readily transmitted and can cause severe economic loss Fusarium oxysporum causes surface rots in stored roots characterised by light to dark brown lesions that tend to be firm dry and superficial The lesions may be circular and centred on wounds caused by insects or mechanical damage at harvest Soft rot caused by Rhizopus stolonifer generally occurs in roots after they are washed and prepared for the market Fungal infection occurs through wounds or bruised tissue producing distinctive tufts of white fungal strands and black spores


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