DiiA is a novel dimorphic cell wall protein of Streptococcus pneumoniae involved in invasive disease.
Many outer multidomain proteins play fundamental virulent roles in an allele-dependent manner. We aimed to investigate the influence of the outer SP1992 protein, here renamed DiiA (Dimorphic invasion-involved A), in pneumococcal disease.



The presence and type of diiA allele was screened by PCR in 560 clinical isolates. Isogenic mutants carrying progressive diiA deletions were constructed and checked in mouse models of infection. DiiA binding to human molecules was carried out by surface plasmon resonance.



The diiA gene is exclusive of Streptococcus pneumoniae and included in the core genome. DiiA variants contain one or two imperfect repeats (R1 and R2), an unstructured region and a cell-wall anchor domain. Clonal complexes carrying both repeats were associated with invasive disease, while those carrying R2 preferentially caused non-invasive syndromes in patients with underlying risk factors. Mutants lacking both repeats were less efficient in nasopharyngeal colonization and dissemination from lungs. Moreover, the ΔdiiA defective strain suffered a severe impairment in bacterial proliferation in blood. Purified DiiA bound to collagen and lactoferrin with high affinity.



DiiA is a distinctive pneumococcal virulence factor contributing to colonization and long-term invasion in this pathogen.
Instituto de Salud Carlos III, Centro Nacional de Microbiología, Carretera a Pozuelo, km 2.2, Majadahonda, 28220 Madrid, Spain.
María S
MS
Escolano-Martínez
CIBER de Enfermedades Respiratorias (CIBERES), Spain; Servicio de Microbiología, Hospital Universitari de Bellvitge, Universitat de Barcelona, IDIBELL, Feixa Llarga, sn. L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
Arnau
A
Domenech
Instituto de Salud Carlos III, Centro Nacional de Microbiología, Carretera a Pozuelo, km 2.2, Majadahonda, 28220 Madrid, Spain; CIBER de Enfermedades Respiratorias (CIBERES), Spain.
José
J
Yuste
Instituto de Salud Carlos III, Centro Nacional de Microbiología, Carretera a Pozuelo, km 2.2, Majadahonda, 28220 Madrid, Spain.
María I
MI
Cercenado
CIBER de Enfermedades Respiratorias (CIBERES), Spain; Servicio de Microbiología, Hospital Universitari de Bellvitge, Universitat de Barcelona, IDIBELL, Feixa Llarga, sn. L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
Carmen
C
Ardanuy
CIBER de Enfermedades Respiratorias (CIBERES), Spain; Servicio de Microbiología, Hospital Universitari de Bellvitge, Universitat de Barcelona, IDIBELL, Feixa Llarga, sn. L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
Josefina
J
Liñares
Instituto de Salud Carlos III, Centro Nacional de Microbiología, Carretera a Pozuelo, km 2.2, Majadahonda, 28220 Madrid, Spain; Presidencia, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Adela G
AG
de la Campa
Instituto de Salud Carlos III, Centro Nacional de Microbiología, Carretera a Pozuelo, km 2.2, Majadahonda, 28220 Madrid, Spain. Electronic address: mgaliano@isciii.es.
Antonio J
AJ
Martin-Galiano
D000328:Adult; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D017353:Gene Deletion; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D013290:Streptococcal Infections / Q000382:microbiology* / Q000473:pathology*; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*; D020349:Surface Plasmon Resonance; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D037521:Virulence Factors; D003094:Collagen; D007781:Lactoferrin
Adhesine; Genomics; Hypothetical protein; Invasion; Vaccine; Virulence factor