NEW YORK (GenomeWeb) – At least some cases of neonatal sepsis or meningitis caused by group B streptococcus appear to involve isolates that have mutated to become virulent following transmission from mothers, according to a study appearing online this week in the Journal of Bacteriology.
In it, French researchers used genome sequencing to characterize 47 isolates of Streptococcus agalactiae, better known as group B streptococcus, a bug that is typically found commensally in the gut and genitourinary tract but which is also among the top culprits in neonatal infection.
By comparing genome sequences in group B streptococcus isolates from 19 mothers and their infants, the team narrowed in on seven small insertions and deletions and 21 SNPs that differed across these pairs, including 14 mutations in the group B streptococcus strains carried by the infants.
Together with gene expression profiles for group B streptococcus isolates grown in human blood, the results suggested that strains in a few of the infants were more apt to carry forms of the bugs with mutations boosting virulence, consistent with apparent adaptation after mother-to-child transmission.
"The mechanism that encourages these virulence mutations is unknown at present," co-corresponding author Claire Poyart, director of INSERM's barriers and pathogens team and researcher at the National Centre for Streptococcus Reference in Paris, said in a statement, noting that there's "an urgent need for better therapeutic interventions against neonatal [group B streptococcus] infections."
Poyart and colleagues used Illumina HiSeq and MiSeq platforms to do whole-genome sequencing on 47 group B streptococcus isolates, representing one to three samples per person from 19 mother-infant pairs at a dozen hospitals in France.
Roughly half of the maternal samples came from amniotic fluid, placental fluid, and vaginal fluid — specimens typically associated with infection-free carriage of the microbe — while 10 maternal isolates were obtained from contaminated milk, blood, or urine samples.
Almost all of the infant samples appeared to be infection-related, appearing in blood, urine, or cerebrospinal fluid. The remaining four isolates came from apparent carriage in the infant gastric fluid.
In all but two of the mother-infant pairs, the team found that infants had group B streptococcus isolates with the same capsular serotype and sequence type as isolates carried by their mothers, consistent with potential maternal transmission of the bugs.
Indeed, in eight of the pairs, mothers and their infants carried group B streptococcus isolates that were genetically identical.
But the team tracked down 21 SNPs and seven indels when it focused on non-identical isolates from nine mother-child pairs, as well as sequential samples taken from one of the infants infected with a strain that differed dramatically from matched maternal samples.
The SNP set included 16 fixed mutations and five polymorphic sites, with 14 mutations appearing specifically in the infant samples.
Comparisons with hundreds of other available group B streptococcus strain sequences indicated that two of the mutations that had become fixed in infant isolates affected the virulence regulatory locus covRS, while one insertion detected in an infant isolate fell in the promoter of a gene coding for an immunogenic surface protein.
The researchers also found two examples of mothers with septicemia who appear to have been infected with group B streptococcus isolates that become more virulent in their infants and were then passed back to them.
Nevertheless, co-senior author Philippe Glaser, leader of the bacterial genomes and evolution group at the Institut Pasteur, noted that the majority of neonatal infections involve group B streptococcus isolates that are innocuous in the mother but virulent in infants. "In most cases, [group B Streptococcus] is just naturally virulent in neonates," he said.