Virulence Factors of <i>Streptococcus pneumoniae</i>. Comparison between African and French Invasive Isolates and Implication for Future Vaccines

<div><p>Background</p><p>Many surface proteins thought to promote <i>Streptocococcus pneumoniae</i> virulence have recently been discovered and are currently being considered as future vaccine targets. We assessed the prevalence of 16 virulence genes among 435 <i>S</i>. <i>pneumoniae</i> 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.</p><p>Methods</p><p>Detection by PCR of <i>pspA</i> (+families), <i>pspC</i> (+<i>pspC</i>.<i>4</i>), <i>pavA</i>, <i>lytA</i>, <i>phtA</i>,<i>B</i>,<i>D</i>,<i>E</i>, <i>nanA</i>,<i>B</i>,<i>C</i>, <i>rrgA</i> (Pilus-1), <i>sipA</i> (Pilus-2), <i>pcpA</i> and <i>psrp</i> was performed on all isolates, as well as antibiotic resistance testing and MLVA typing (+MLST on 54 representative strains). Determination of <i>ply</i> alleles was performed by sequencing (Sp1 isolates).</p><p>Results</p><p>MLVA and virulence genes profiles segregated Sp1 isolates into 2 groups that followed continent distribution. The <i>ply</i> allele 5 and most of the genes that were variable (<i>nanC</i>, Pilus-2, <i>psrp</i>, <i>pcpA</i>, <i>phtD</i>) were present in the French Sp1 isolates (PMEN clone Sweden¹-28, 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 <i>psrp</i> were more prevalent in bacteraemic pneumonia yielded isolates and <i>phtB</i> in meningitis-related isolates. Considering vaccine candidates, <i>phtD</i> was less prevalent than anticipated (50%) and <i>pcpA</i> varied importantly between France and Africa (98% versus 34%). Pilus-1 was carried by 7-11% of isolates and associated with β-lactams resistance.</p><p>Conclusions</p><p>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.</p>