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Walid Mohamed

Publications and source records attributed to Walid Mohamed.

4 recordsLinked to original sources

The MprF protein is required for lysinylation of phospholipids in listerial membranes and confers resistance to cationic antimicrobial peptides (CAMPs) on Listeria monocytogenes.

Pathogenic bacteria have to cope with defence mechanisms mediated by adaptive and innate immunity of the host cells. Cationic antimicrobial peptides (CAMPs) represent one of the most effective components of the host innate immune response. Here we establish the function of Lmo1695, a member of the VirR-dependent virulence regulon, recently identified in Listeria monocytogenes. Lmo1695 encodes a membrane protein of 98 kDa with strong homology to the multiple peptide resistance factor (MprF) of Staphylococcus aureus. Like staphylococcal MprF, we found that Lmo1695 is involved in the synthesis of the membrane phospholipid lysylphosphatidylglycerol (L-PG). In addition, Lmo1695 is also essential for lysinylation of diphosphatidylglycerol (DPG), another phospholipid widely distributed in bacterial membranes. A Deltalmo1695 mutant lacking the lysinylated phospholipids was particularly susceptible to CAMPs of human and bacterial origin. The mutant strain infected both epithelial cells and macrophages only poorly and was attenuated for virulence when tested in a mouse model of infection. Lmo1695 is a member of a growing list of survival factors which enable growth of L. monocytogenes in different environments.

Animals↗

The ferritin-like protein Frm is a target for the humoral immune response to Listeria monocytogenes and is required for efficient bacterial survival.

The identity and role of listerial antigens recognized by antibodies following listerial infection is largely unknown. We identified the listerial ferritin-like protein Frm as a target of the humoral response following infection of mice with pathogenic Listeria monocytogenes. Specific antibodies to Frm are detected in antisera of mice infected with a pathogenic strain but not in antisera of mice infected with a non-pathogenic L. innocua strain. Antibodies raised to purified listerial ferritin allowed us to demonstrate that the expression of Frm is both growth phase- and temperature-dependent. Using an isogenic Deltafrm mutant, we find that ferritin is essential for bacterial growth in chemically defined minimal media but not in complex media such as brain-heart infusion. Mutant bacteria also exhibit a defect in intracellular replication. The Deltafrm strain is hypersensitive to hydrogen peroxide indicating that the Frm is required for protection against reactive oxygen intermediates under various growth conditions. Animal studies show that Frm contributes to pathogenesis in mice, in particular, at early time points following infection.

Animals↗

Human infective endocarditis caused by Streptococcus suis serotype 2.

Human infective endocarditis due to Streptococcus suis occurs infrequently. The case of a 43-year-old male who sustained life-threatening infective endocarditis is reported. Since growth of S. suis on commonly used sheep blood agar plates resembles viridans streptococci, diagnosis of S. suis constitutes a diagnostic pitfall. Identification was accomplished by using molecular methods.

Adult↗

Induction of immune responses by attenuated isogenic mutant strains of Listeria monocytogenes.

We have generated isogenic Listeria monocytogenes mutant strains to study the induction of protective immunity in mice. These strains harbored either a specific deletion within the actin nucleator (actA) and/or have multiple deletions within the actA and phospholipase B (plcB) genes. In comparison to the wild type parental L. monocytogenes EGDe strains, the mutant strains were extremely low in virulence and were rapidly eliminated by the host during the first days of infection. Nevertheless, a single immunization with both mutant strains (EGDe DeltaactA2 and DeltaactADeltaplcB) efficiently induced and maintained effector memory (CD8(+)) T cells and has provided animals with a state of long-lasting protective immunity against wild type L. monocytogenes. These mutant strains can be used as live vaccines against the corresponding virulent pathogen and as carriers for introducing heterologous protective antigens into animals and humans.

Animals↗