title: Bacillus anthracis Overcomes an Amino Acid Auxotrophy by Cleaving Host Serum Proteins.
abstract: Bacteria sustain an infection by acquiring nutrients from the host to support replication. The host sequesters these nutrients as a growth-restricting strategy, a concept termed "nutritional immunity." Historically, the study of nutritional immunity has centered on iron uptake because many bacteria target hemoglobin, an abundant circulating protein, as an iron source. Left unresolved are the mechanisms that bacteria use to attain other nutrients from host sources, including amino acids. We employed a novel medium designed to mimic the chemical composition of human serum, and we show here that Bacillus anthracis, the causative agent of anthrax disease, proteolyzes human hemoglobin to liberate essential amino acids which enhance its growth. This property can be traced to the actions of InhA1, a secreted metalloprotease, and extends to at least three other serum proteins, including serum albumin. The results suggest that we must also consider proteolysis of key host proteins to be a way for bacterial pathogens to attain essential nutrients, and we provide an experimental framework to determine the host and bacterial factors involved in this process.
  
  
  OBJECTIVE
  The mechanisms by which bacterial pathogens acquire nutrients during infection are poorly understood. Here we used a novel defined medium that approximates the chemical composition of human blood serum, blood serum mimic (BSM), to better model the nutritional environment that pathogens encounter during bacteremia. Removing essential amino acids from BSM revealed that two of the most abundant proteins in blood-hemoglobin and serum albumin-can satiate the amino acid requirement for Bacillus anthracis, the causative agent of anthrax. We further demonstrate that hemoglobin is proteolyzed by the secreted protease InhA1. These studies highlight that common blood proteins can be a nutrient source for bacteria. They also challenge the historical view that hemoglobin is solely an iron source for bacterial pathogens.
authors.affiliation: Molecular Virology and Microbiology Department, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Austen
authors.initials: A
authors.lastname: Terwilliger
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Swick
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Pflughoeft
authors.affiliation: National Institute of Allergy and Infectious Diseases, Microbial Pathogenesis Section, Bethesda, Maryland, USA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Pomerantsev
authors.affiliation: Infectious Disease Research Complex, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: C Rick
authors.initials: CR
authors.lastname: Lyons
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Koehler
authors.affiliation: Molecular Virology and Microbiology Department, Baylor College of Medicine, Houston, Texas, USA maresso@bcm.edu.
authors.forename: Anthony
authors.initials: A
authors.lastname: Maresso
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism*; D001408:Bacillus anthracis / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism*; D003470:Culture Media / Q000737:chemistry; D006418:Heme / Q000378:metabolism; D006454:Hemoglobins; D006801:Humans; D007501:Iron / Q000378:metabolism; D008969:Molecular Sequence Data; D044967:Serum / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D001798:Blood Proteins; D003470:Culture Media; D006454:Hemoglobins; D006418:Heme; D007501:Iron