Ricerc@Sapienza

Brucella microti was isolated a decade ago from wildlife and soil in Europe. Compared to the classical Brucella species, it exhibits atypical virulence properties such as increased growth in human and murine macrophages and lethality in experimentally infected mice. A spontaneous rough (R) mutant strain, derived from the smooth reference strain CCM4915T, showed increased macrophage colonization and was non-lethal in murine infections. Whole-genome sequencing and construction of an isogenic mutant of B.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 is responsible of many kinds of infections of skin and soft-tissue. Antibiotic resistance, biofilm formation and the ability to adhere and invade are virulence factors that contribute to MRSA pathogenesis. In some cases, decreased bioavailability of antibiotics in systemic circulation could result; in these conditions sub-therapeutic levels of the antibiotics may be established, exposing bacteria to sub-inhibitory concentrations.

Efflux pumps represent an important and large group of transporter proteins found in all organisms. The importance of efflux pumps resides in their ability to extrude a wide range of antibiotics, resulting in the emergence of multidrug resistance in many bacteria. Besides antibiotics, multidrug efflux pumps can also extrude a large variety of compounds: Bacterial metabolites, plant-produced compounds, quorum-sensing molecules, and virulence factors. This versatility makes efflux pumps relevant players in interactions not only with other bacteria, but also with plant or animal cells.

Lipopolysaccharide (LPS) is an essential structural component of the outer membrane (OM) of most Gram-negative bacteria. In the model organism Escherichia coli, LPS transport to the OM requires seven essential proteins (LptABCDEFG) that form a continuous bridge across the cell envelope. In Pseudomonas aeruginosa the recently-demonstrated essentiality of LptD and LptH, the P. aeruginosa LptA homologue, confirmed the crucial role of the Lpt system and, thus, of LPS in OM biogenesis in this species. Surprisingly, independent high-throughput transposon mutagenesis studies identified viable P.

Modifications of the lipid A moiety of lipopolysaccharide influence the physicochemical properties of the outer membrane of Gram-negative bacteria. Some bacteria produce lipid A with a single hydroxylated secondary acyl chain. This hydroxylation is catalyzed by the dioxygenase LpxO, and is important for resistance to cationic antimicrobial peptides (e.g., polymyxins), survival in human blood, and pathogenicity in animal models.

Colistin represents the last-line treatment option against many multidrug-resistant Gram-negative pathogens. Several lines of evidence indicate that aminoarabinosylation of the lipid A moiety of lipopolysaccharide (LPS) is an essential step for the development of colistin resistance in Pseudomonas aeruginosa. However, whether it is sufficient to confer resistance in this bacterium remains unclear. The aim of this work was to investigate the specific contribution of lipid A aminoarabinosylation to colistin resistance in P.