Lysine-modified phospholipids important for virulence and survival of L. monocytogenes
The intracellular, foodborne gastrointestinal pathogen Listeria monocytogenes is primarily responsible for causing listeriosis or food poisoning in otherwise healthy individuals. Infections during pregnancy or within immune compromised individuals can be very serious, with the risk of fetal termination or fetal fatality postpartum in the former and septicemia or meningitis with a 20% fatality rate in the latter group. The roles of internalin proteins and listeriolysin-O in the infection process are well characterized, but little is known about the specific roles of lysine-modified phospholipids in the membrane of L. monocytogenes. A recent study investigating the lipid bilayer composition of L. monocytogenes indicated that the overall proportions of lipids, including lysylcardiolipin and lysylphosphatidylglycerol (LysPG), vary with growth temperature and growth phase. Dr Michael Ibba and his colleagues showed that LysPG formation is essential for L. monocytogenes survival in the presence of increased osmolytic stress but has no effect on bacterial adherence, invasion or survival in the presence of physiologically relevant concentrations of human neutrophil peptide (HNP-1). In the absence of LysPG synthesis, L. monocytogenes unexpectedly retained flagellum-mediated motility at 37 °C. In summary, these findings show that LysPG formation in L. monocytogenes has broader functions in virulence and survival beyond its known role in the modification of membrane potential previously observed in other bacteria.
Reference
Dare K, Shepherd J, Roy H, Seveau S, Ibba M. LysPGS formation in Listeria monocytogenes has broad roles in maintaining membrane integrity beyond antimicrobial peptide resistance. Virulence 2014; 5(4): 534–546; http://dx.doi.org/10.4161/viru.28359
Rotavirus immunity and the success of rotavirus vaccination
Acute gastroenteritis is a major killer of the very young worldwide. Rotavirus is the most common intestinal virus, causing acute gastroenteritis and extra-intestinal complications especially in young and chronically ill subjects. As early as 1991, the WHO recommended as high priority the development of a vaccine against rotavirus, the major pathogen causing enteric infections. Since the introduction of rotavirus vaccines for infant immunization programmes in different parts of the world in 2006, vaccination against rotavirus has resulted in substantial declines in severe gastroenteritis. The oral rotavirus vaccines RotaTeq® and Rotarix® are excellent examples for their unique features and principles of mucosal immunization. A recent review by Dr Markus Rose elaborates on rotavirus immunity and the success of rotavirus vaccination and aspects also beyond infants’ acute gastroenteritis.
Reference
Rose MA. Mucosal Immunity and acute viral gastroenteritis: The example rotavirus. Hum Vaccin Immunother 2014; 10(7): 2112–2114; http://dx.doi.org/10.4161/hv.29605
Mucosal VP6-specific IgA antibodies inhibit rotavirus infection in vitro
Rotavirus (RV) is a common cause of severe gastroenteritis (GE) in children worldwide. Live oral RV vaccines protect against severe RVGE, but the immune correlates of protection are not yet clearly defined. Inner capsid VP6 protein is a highly conserved, abundant, and immunogenic RV protein, and VP6-specific mucosal antibodies, especially IgA, have been implicated to protect against viral challenge in mice. In a recent study, systemic and mucosal IgG and IgA responses were induced by immunizing BALB/c mice intranasally with a combination of recombinant RV VP6 protein and norovirus virus-like particles used in a candidate vaccine. Following immunization mice were challenged orally with a murine RV strain. Neutralizing activity of fecal samples, sera, and vaginal washes against human RV and rhesus RV was measured with an ELISA-based antigen reduction neutralization assay. The researchers led by Dr Vesna Blazevic found that only vaginal washes of immunized mice inhibited replication of both RVs, indicating heterotypic protection of induced antibodies. IgA antibody depletion and blocking experiments using recombinant VP6 confirmed that neutralization was mediated by anti-VP6 IgA antibodies. Most importantly, after the RV challenge significant reduction in viral shedding was observed in feces of immunized mice. The results of this study suggest a significant role for mucosal RV VP6-specific IgA for the inhibition of RV replication in vitro and in vivo. In addition, these results underline the importance of non-serotype-specific immunity induced by the conserved subgroup-specific RV antigen VP6 in clearance of RV infection.
Reference
Lappalainen S, Pastor AR, Tamminen K, López-Guerrero V, Esquivel-Guadarrama F, Palomares LA, Vesikari T, Blazevic V. Immune responses elicited against rotavirus middle layer protein VP6 inhibit viral replication in vitro and in vivo. Hum Vaccin Immunother 2014; 10(7): 2039–2047; http://dx.doi.org/10.4161/hv.28858
L. monoytogenes interferes with host cell cycle progression to promote infection
The facultative intracellular, foodborne pathogen Listeria monocytogenes is able to cross tight human barriers and spread from cell to cell, causing listeriosis, a severe human disease. It is known that several bacterial pathogens, including Shigella, Escherichia coli or Helicobacter pylori, modulate the host cell cycle to support infection. As pathogens often exploit similar pathways to cause infection, a recent study set out to investigate if L. monocytogenes also interferes with the host cell cycle progression to create a suitable replication niche. Together with their co-workers, Drs Didier Cabanes and Sandra Sousa showed that L. monocytogenes infection indeed affects the host cell cycle progression, increasing its overall duration but allowing consecutive rounds of division. A complete L. monocytogenes infectious cycle induced a S-phase delay accompanied by a slower rate of DNA synthesis and increased levels of host DNA strand breaks. Additionally, DNA damage/replication checkpoint responses were triggered in a L. monocytogenes dose-dependent manner through the phosphorylation of the DNA-dependent protein kinase DNA-PK, histone H2A.X, and the phosphatase CDC25A and independently from the serine/threonine protein kinases ATM/ATR. While exogenously induced host DNA damage favored dissemination of L. monocytogenes, the override of checkpoint pathways limited infection. The authors propose that host DNA replication disturbed by L. monocytogenes infection culminates in DNA strand breaks, triggering DNA damage/replication responses, and ensuring a cell cycle delay that favors L. monocytogenes propagation.
Reference
Leitão E, Costa AC, Brito C, Costa L, Pombinho R, Cabanes D, Sousa S. Listeria monocytogenes induces host DNA damage and delays the host cell cycle to promote infection. Cell Cycle 2014; 13(6): 928–940; http://dx.doi.org/10.4161/cc.27780