title: Virulence Factors of Streptococcus pneumoniae. Comparison between African and French Invasive Isolates and Implication for Future Vaccines.
abstract: BACKGROUND
  Many surface proteins thought to promote Streptocococcus pneumoniae virulence have recently been discovered and are currently being considered as future vaccine targets. We assessed the prevalence of 16 virulence genes among 435 S. pneumoniae invasive isolates from France and the "African meningitis belt" region, with particular focus on serotype 1 (Sp1), to compare their geographical distribution, assess their association with site of infection and evaluate their potential interest as new vaccine candidates.
  
  
  METHODS
  Detection by PCR of pspA (+families), pspC (+pspC.4), pavA, lytA, phtA,B,D,E, nanA,B,C, rrgA (Pilus-1), sipA (Pilus-2), pcpA and psrp was performed on all isolates, as well as antibiotic resistance testing and MLVA typing (+MLST on 54 representative strains). Determination of ply alleles was performed by sequencing (Sp1 isolates).
  
  
  RESULTS
  MLVA and virulence genes profiles segregated Sp1 isolates into 2 groups that followed continent distribution. The ply allele 5 and most of the genes that were variable (nanC, Pilus-2, psrp, pcpA, phtD) were present in the French Sp1 isolates (PMEN clone Sweden(1)-28, ST306) but absent from the African ones. Whereas all African Sp1 isolates clustered into a single MLST CC (CC217), MLVA distinguished two CCs that followed temporal evolution. Pilus-2 and psrp were more prevalent in bacteraemic pneumonia yielded isolates and phtB in meningitis-related isolates. Considering vaccine candidates, phtD was less prevalent than anticipated (50%) and pcpA varied importantly between France and Africa (98% versus 34%). Pilus-1 was carried by 7-11% of isolates and associated with β-lactams resistance.
  
  
  CONCLUSIONS
  Most virulence genes were carried by the European ST306 clone but were lacking on Sp1 isolates circulating in the African meningitis belt, where a more serious pattern of infection is observed. While virulence proteins are now considered as vaccine targets, the geographical differences in their prevalence could affect the efficacy expected from future vaccines.
authors.affiliation: Paediatric Infectious Diseases Unit, Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Blumental
authors.affiliation: Molecular Biology Lab, Biology Department, Hôpital d'Instruction des Armées Robert Picqué, Bordeaux, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Granger-Farbos
authors.affiliation: Agence de Médecine Préventive, Paris, France.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Moïsi
authors.affiliation: Molecular Biology Lab, Biology Department, Hôpital d'Instruction des Armées Robert Picqué, Bordeaux, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Soullié
authors.affiliation: Molecular Biology Lab, Biology Department, Hôpital d'Instruction des Armées Robert Picqué, Bordeaux, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Leroy
authors.affiliation: Agence de Médecine Préventive, Paris, France.
authors.forename: Berthe-Marie
authors.initials: BM
authors.lastname: Njanpop-Lafourcade
authors.affiliation: Centre Muraz, Bobo-Dioulasso, Burkina Faso.
authors.forename: Seydou
authors.initials: S
authors.lastname: Yaro
authors.affiliation: Paediatric Unit, Centre Hospitalier Universitaire Sourô Sanou, Bobo-Dioulasso, Burkina Faso.
authors.forename: Boubacar
authors.initials: B
authors.lastname: Nacro
authors.affiliation: Centre for Molecular Diagnosis, IRIS Lab, Brussels, Belgium.
authors.forename: Marie
authors.initials: M
authors.lastname: Hallin
authors.affiliation: Molecular Biology Lab, Biology Department, Hôpital d'Instruction des Armées Robert Picqué, Bordeaux, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Koeck
mesh_terms: D000349:Africa; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D005602:France; D006801:Humans; D008586:Meningitis, Pneumococcal / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D008826:Microbial Sensitivity Tests; D058885:Multilocus Sequence Typing; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control; D022541:Streptococcal Vaccines / Q000235:genetics / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D022541:Streptococcal Vaccines; D037521:Virulence Factors