title: Signatures of conformational stability and oxidation resistance in proteomes of pathogenic bacteria.
abstract: Protein oxidation is known to compromise vital cellular functions. Therefore, invading pathogenic bacteria must resist damage inflicted by host defenses via reactive oxygen species. Using comparative genomics and experimental approaches, we provide multiple lines of evidence that proteins from pathogenic bacteria have acquired resistance to oxidative stress by an increased conformational stability. Representative pathogens exhibited higher survival upon HSP90 inhibition and a less-oxidation-prone proteome. A proteome signature of the 46 pathogenic bacteria encompasses 14 physicochemical features related to increasing protein conformational stability. By purifying ten representative proteins, we demonstrate in vitro that proteins with a pathogen-like signature are more resistant to oxidative stress as a consequence of their increased conformational stability. A compositional signature of the pathogens' proteomes allowed the design of protein fragments more resilient to both unfolding and carbonylation, validating the relationship between conformational stability and oxidability with implications for synthetic biology and antimicrobial strategies.
authors.affiliation: Mediterranean Institute for Life Sciences, Mestrovicevo setaliste 45, 21000 Split, Croatia.
authors.forename: Anita
authors.initials: A
authors.lastname: Vidovic
authors.affiliation: Division of Electronics, Rudjer Boskovic Institute, Bijenicka cesta 54, 10000 Zagreb, Croatia; EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain.
authors.forename: Fran
authors.initials: F
authors.lastname: Supek
authors.affiliation: Mediterranean Institute for Life Sciences, Mestrovicevo setaliste 45, 21000 Split, Croatia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Nikolic
authors.affiliation: Mediterranean Institute for Life Sciences, Mestrovicevo setaliste 45, 21000 Split, Croatia. Electronic address: anita.krisko@medils.hr.
authors.forename: Anita
authors.initials: A
authors.lastname: Krisko
mesh_terms: D001419:Bacteria / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress; D011487:Protein Conformation; D055550:Protein Stability; D020543:Proteome / Q000737:chemistry* / Q000378:metabolism; D014774:Virulence / Q000235:genetics
chemical_list: D018841:HSP90 Heat-Shock Proteins; D020543:Proteome