To survive in the iron-devoid environment of their host, pathogenic bacteria have devised multifarious cunning tactics such as evolving intricate heme transport systems to pirate extracellular heme. Yet, the potential of heme transport systems as antimicrobial targets has not been explored. Herein we developed a strategy to deliver antimicrobials by exploiting the extracellular heme acquisition system protein A (HasA) of . We demonstrated that, analogous to heme uptake, HasA can specifically traffic an antimicrobial, gallium phthalocyanine (GaPc), into the intracellular space of the interaction of HasA with its outer membrane receptor HasR. HasA enables water-insoluble GaPc to be mistakenly acquired by , permitting its sterilization (>99.99%) by irradiation with near-infrared (NIR) light, irrespective of antibiotic resistance. Our findings substantiate that bacterial heme uptake protein-protein recognition is an attractive target for antimicrobials, enabling specific and effective sterilization.
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http://dx.doi.org/10.1021/acschembio.9b00373 | DOI Listing |
Commun Biol
January 2025
Faculty of Science, Ibaraki University, Mito, Japan.
Halorhodospira (Hlr.) halophila strain BN9622 is an extremely halophilic and alkaliphilic purple phototrophic bacterium and has been widely used as a model for exploring the osmoadaptive and photosynthetic strategies employed by phototrophic extreme halophiles that enable them to thrive in hypersaline environments. Here we present the cryo-EM structures of (1) a unique native Hlr.
View Article and Find Full Text PDFEvol Med Public Health
December 2024
Department of Anthropology, Michigan State University, East Lansing, MI, USA.
Background And Objectives: The optimal iron hypothesis (OIH) posits that risk for infection is lowest at a mild level of iron deficiency. The extent to which this protection results from arms race dynamics in the evolution of iron acquisition and sequestration mechanisms is unclear. We evaluated the OIH with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an emerging infectious agent.
View Article and Find Full Text PDFChembiochem
December 2024
Friedrich-Schiller-Universitat Jena, Institute of Physical Chemistry, GERMANY.
Heme is involved in many critical processes in pathogenic bacteria as iron acquisition by these microorganisms is achieved by either direct uptake of heme or use of heme-binding proteins called hemophores. Exploring the underlying mechanisms on a molecular level can open new avenues in understanding the host-pathogen interactions. Any imbalance of the heme concentration has a direct impact on the bacterial growth and survival.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095.
To successfully mount infections, nearly all bacterial pathogens must acquire iron, a key metal cofactor that primarily resides within human hemoglobin. causes the life-threatening respiratory disease diphtheria and captures hemoglobin for iron scavenging using the surface-displayed receptor HbpA. Here, we show using X-ray crystallography, NMR, and in situ binding measurements that selectively captures iron-loaded hemoglobin by partially ensconcing the heme molecules of its α subunits.
View Article and Find Full Text PDFJ Fungi (Basel)
November 2024
Department of Molecular Biotechnology and Microbiology, Institute of Biotechnology, Faculty of Science and Technology, University of Debrecen, H-4032 Debrecen, Hungary.
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