Evolving serodiagnostics by rationally designed peptide arrays: the Burkholderia paradigm in Cystic Fibrosis.
Efficient diagnosis of emerging and novel bacterial infections is fundamental to guide decisions on therapeutic treatments. Here, we engineered a novel rational strategy to design peptide microarray platforms, which combines structural and genomic analyses to predict the binding interfaces between diverse protein antigens and antibodies against Burkholderia cepacia complex infections present in the sera of Cystic Fibrosis (CF) patients. The predicted binding interfaces on the antigens are synthesized in the form of isolated peptides and chemically optimized for controlled orientation on the surface. Our platform displays multiple Burkholderia-related epitopes and is shown to diagnose infected individuals even in presence of superinfections caused by other prevalent CF pathogens, with limited cost and time requirements. Moreover, our data point out that the specific patterns determined by combined probe responses might provide a characterization of Burkholderia infections even at the subtype level (genomovars). The method is general and immediately applicable to other bacteria.
Istituto di Chimica del Riconoscimento Molecolare, ICRM, CNR. Via Mario Bianco 9, 20131, Milano (Italy).
Claudio
C
Peri
Istituto di Chimica del Riconoscimento Molecolare, ICRM, CNR. Via Mario Bianco 9, 20131, Milano (Italy).
Alessandro
A
Gori
Istituto di Chimica del Riconoscimento Molecolare, ICRM, CNR. Via Mario Bianco 9, 20131, Milano (Italy).
Paola
P
Gagni
Istituto di Chimica del Riconoscimento Molecolare, ICRM, CNR. Via Mario Bianco 9, 20131, Milano (Italy).
Laura
L
Sola
Cystic Fibrosis Microbiology Laboratory, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, via San Barnaba 8, 20122, Milano (Italy).
Daniela
D
Girelli
Cystic Fibrosis Microbiology Laboratory, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, via San Barnaba 8, 20122, Milano (Italy).
Samantha
S
Sottotetti
Cystic Fibrosis Microbiology Laboratory, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, via San Barnaba 8, 20122, Milano (Italy).
Lisa
L
Cariani
Istituto di Chimica del Riconoscimento Molecolare, ICRM, CNR. Via Mario Bianco 9, 20131, Milano (Italy).
Marcella
M
Chiari
Istituto di Chimica del Riconoscimento Molecolare, ICRM, CNR. Via Mario Bianco 9, 20131, Milano (Italy).
Marina
M
Cretich
Istituto di Chimica del Riconoscimento Molecolare, ICRM, CNR. Via Mario Bianco 9, 20131, Milano (Italy).
Giorgio
G
Colombo
D000907:Antibodies, Bacterial / Q000737:chemistry; D000942:Antigens, Bacterial / Q000737:chemistry / Q000378:metabolism; D015373:Bacterial Typing Techniques; D019121:Burkholderia Infections / Q000175:diagnosis* / Q000276:immunology; D042602:Burkholderia cepacia complex / Q000276:immunology*; D003550:Cystic Fibrosis / Q000097:blood / Q000382:microbiology*; D006801:Humans; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D040081:Protein Array Analysis / Q000379:methods; D012680:Sensitivity and Specificity
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D010455:Peptides