Digalactoside expression in the lipopolysaccharide of Haemophilus influenzae and its role in intravascular survival.

Digalactoside (galalpha-1-4 galbeta) structures of the lipopolysaccharide (LPS) of Haemophilus influenzae are implicated in virulence. A confounding factor is that tetranucleotide repeats within the lic2A, lgtC, and lex2 genes mediate phase-variable expression of the digalactosides. By deleting these repeats, we constructed recombinant strains of RM153 constitutively expressing either one or two LPS digalactosides. Expression of two digalactosides, rather than one, was associated with increased virulence of H. influenzae in vivo.

Genetic islands of Streptococcus agalactiae strains NEM316 and 2603VR and their presence in other Group B streptococcal strains.

BACKGROUND: Streptococcus agalactiae (Group B Streptococcus; GBS) is a major contributor to obstetric and neonatal bacterial sepsis. Serotype III strains cause the majority of late-onset sepsis and meningitis in babies, and thus appear to have an enhanced invasive capacity compared with the other serotypes that cause disease predominantly in immunocompromised pregnant women. We compared the serotype III and V whole genome sequences, strains NEM316 and 2603VR respectively, in an attempt to identify genetic attributes of strain NEM316 that might explain the propensity of strain NEM316 to cause late-onset disease in babies. Fourteen putative pathogenicity islands were described in the strain NEM316 whole genome sequence. Using PCR- and targeted microarray- strategies, the presence of these islands were assessed in a diverse strain collection including 18 colonizing isolates from healthy pregnant women, and 13 and 8 invasive isolates from infants with early- and late-onset sepsis, respectively. RESULTS: Side-by-side comparison of the strain NEM316 and strain 2603VR genomes revealed that they are extremely similar, with the only major difference being the capsulation loci and mobile genetic elements. PCR and Comparative Genome Hybridization (CGH) were used to define the presence of each island in 39 GBS isolates. Only islands I, VI, XII, and possibly X, met criteria of a true pathogenicity island, but no significant correlation was found between the presence of any of the fourteen islands and whether the strains were invasive or colonizing. Possible associations were seen between the presence of island VI and late-onset sepsis, and island X and early-onset sepsis, which warrant further investigation. CONCLUSION: The NEM316 and 2603VR strains are remarkable in that their whole genome sequences are so similar, suggesting that the capsulation loci or other genetic differences, such as pathogenicity islands, are the main determinants of the propensity of serotype III strains to cause late-onset disease. This study supports the notion that GBS strain NEM316 has four putative pathogenicity islands, but none is absolutely necessary for disease causation, whether early- or late-onset sepsis. Mobile genetic elements are a common feature of GBS isolates, with each strain having its own peculiar burden of transposons, phages, integrases and integrated plasmids. The majority of these are unlikely to influence the disease capacity of an isolate. Serotype associated disease phenotypes may thus be solely related to differences in the capsulation loci.

Bacterial virulence factors in neonatal sepsis: group B streptococcus.

PURPOSE OF REVIEW: Group B streptococcus is a leading cause of neonatal pneumonia, septicaemia and meningitis. Up to one quarter of women in labour are now given intravenous antibiotics to prevent early-onset disease by the organism, a situation that will remain constant until a successful vaccine is available. From a molecular understanding of the pathogenicity of group B streptococcus we may be able to devise novel means for controlling disease, such as identifying inhibitors of key metabolic pathways or regulatory networks. This review summarizes our post-genomic knowledge of the regulation, metabolism and virulence of group B streptococcus. RECENT FINDINGS: Although advances have been made in the understanding of classic group B streptococcus virulence traits, such as capsular polysaccharide, beta-haemolysin, C5a peptidase, adhesins and immunogenic surface proteins, the major recent contribution to group B streptococcus pathogenesis has been the whole genome sequencing of three group B streptococcus strains, representing serotypes Ia, III and V. From these genomes, we not only see where the classic virulence genes map, but we can also gain insights into the metabolism and regulation of the organism and how these affect its virulence. SUMMARY: Knowledge of virulence factors and the organism's metabolism and gene regulation offers opportunities to find novel means of preventing group B streptococcus infection in babies.

Evidence for extensive transmission distortion in the human genome.

It is a basic principle of genetics that each chromosome is transmitted from parent to offspring with a probability that is given by Mendel's laws. However, several known biological processes lead to skewed transmission probabilities among surviving offspring and, therefore, to excess genetic sharing among relatives. Examples include in utero selection against deleterious mutations, meiotic drive, and maternal-fetal incompatibility. Although these processes affect our basic understanding of inheritance, little is known about their overall impact in humans or other mammals. In this study, we examined genome screen data from 148 nuclear families, collected without reference to phenotype, to look for departures from Mendelian transmission proportions. Using single-point and multipoint linkage analysis, we detected a modest but significant genomewide shift towards excess genetic sharing among siblings (average sharing of 50.43% for the autosomes; P=.009). Our calculations indicate that many loci with skewed transmission are required to produce a genomewide shift of this magnitude. Since transmission distortion loci are subject to strong selection, this raises interesting questions about the evolutionary forces that keep them polymorphic. Finally, our results also have implications for mapping disease genes and for the genetics of fertility.