Exploring host-pathogen interactions through genome wide protein microarray analysis.
During bacterial pathogenesis extensive contacts between the human and the bacterial extracellular proteomes take place. The identification of novel host-pathogen interactions by standard methods using a case-by-case approach is laborious and time consuming. To overcome this limitation, we took advantage of large libraries of human and bacterial recombinant proteins. We applied a large-scale protein microarray-based screening on two important human pathogens using two different approaches: (I) 75 human extracellular proteins were tested on 159 spotted Staphylococcus aureus recombinant proteins and (II) Neisseria meningitidis adhesin (NadA), an important vaccine component against serogroup B meningococcus, was screened against ≈2300 spotted human recombinant proteins. The approach presented here allowed the identification of the interaction between the S. aureus immune evasion protein FLIPr (formyl-peptide receptor like-1 inhibitory protein) and the human complement component C1q, key players of the offense-defense fighting; and of the interaction between meningococcal NadA and human LOX-1 (low-density oxidized lipoprotein receptor), an endothelial receptor. The novel interactions between bacterial and human extracellular proteins here presented might provide a better understanding of the molecular events underlying S. aureus and N. meningitidis pathogenesis.
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Luigi
L
Scietti
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Katia
K
Sampieri
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Irene
I
Pinzuti
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Erika
E
Bartolini
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Barbara
B
Benucci
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Alessia
A
Liguori
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Andreas F
AF
Haag
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Paola
P
Lo Surdo
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Werner
W
Pansegrau
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Vincenzo
V
Nardi-Dei
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Laura
L
Santini
Novartis Institutes for Biomedical Research, Novartis Campus, 4056 Basel, Switzerland.
Seguinde
S
Arora
Novartis Institutes for Biomedical Research, Novartis Campus, 4056 Basel, Switzerland.
Xavier
X
Leber
Department of Molecular Medicine, Unit of Biochemistry, Viale Taramelli 3/b, 27100 Pavia, Italy.
Simonetta
S
Rindi
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Silvana
S
Savino
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Paolo
P
Costantino
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Domenico
D
Maione
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.|University of Naples "Federico II", Department of Biology, via Cinthia 4, 80126 Naples, Italy.
Marcello
M
Merola
Department of Molecular Medicine, Unit of Biochemistry, Viale Taramelli 3/b, 27100 Pavia, Italy.
Pietro
P
Speziale
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Matthew J
MJ
Bottomley
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Fabio
F
Bagnoli
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Vega
V
Masignani
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Mariagrazia
M
Pizza
Novartis Institutes for Biomedical Research, Novartis Campus, 4056 Basel, Switzerland.
Meike
M
Scharenberg
Novartis Institutes for Biomedical Research, Novartis Campus, 4056 Basel, Switzerland.
Jean-Marc
JM
Schlaeppi
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Mikkel
M
Nissum
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Sabrina
S
Liberatori
D018829:Adhesins, Bacterial / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001665:Binding Sites; D016466:CHO Cells; D015922:Complement C1q / Q000378:metabolism; D003412:Cricetulus; D054884:Host-Pathogen Interactions; D006801:Humans; D009345:Neisseria meningitidis / Q000502:physiology*; D040081:Protein Array Analysis / Q000379:methods*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000378:metabolism; D013211:Staphylococcus aureus / Q000502:physiology*
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; C516018:FPRL1 inhibitory protein, S aureus; C501982:NadA protein, Neisseria meningitidis; C495137:OLR1 protein, human; D011994:Recombinant Proteins; D051127:Scavenger Receptors, Class E; D015922:Complement C1q