Unravelling the Roles of Bacterial Nanomachines Bistability in Pathogens' Life Cycle.

Bacterial nanomachines represent remarkable feats of evolutionary engineering, showcasing intricate molecular mechanisms that enable bacteria to perform a diverse array of functions essential to persist, thrive, and evolve within ecological and pathological niches. Injectosomes and bacterial flagella represent two categories of bacterial nanomachines that have been particularly well studied both at the molecular and functional levels. Among the diverse functionalities of these nanomachines, bistability emerges as a fascinating phenomenon, underscoring their dynamic and complex regulation as well as their contribution to shaping the bacterial community behavior during the infection process.

The macrophage-bacterium mismatch in persister formation.

Many pathogens are hard to eradicate, even in the absence of genetically detectable antimicrobial resistance mechanisms and despite proven antibiotic susceptibility. The fraction of clonal bacteria that temporarily elude effective antibiotic treatments is commonly known as 'antibiotic persisters.' Over the past decade, there has been a growing body of research highlighting the pivotal role played by the cellular host in the development of persisters.

Intracellular persister: A stealth agent recalcitrant to antibiotics.

The bulk of bacteria transiently evading appropriate antibiotic regimes and recovered from non-resolutive infections are commonly refer to as persisters. In this mini-review, we discuss how antibiotic persisters stem from the interplay between the pathogen and the cellular defenses mechanisms and its underlying heterogeneity.

Quorum sensing governs a transmissive Legionella subpopulation at the pathogen vacuole periphery.

The Gram-negative bacterium Legionella pneumophila is the causative agent of Legionnaires' disease and replicates in amoebae and macrophages within a distinct compartment, the Legionella-containing vacuole (LCV). The facultative intracellular pathogen switches between a replicative, non-virulent and a non-replicating, virulent/transmissive phase. Here, we show on a single-cell level that at late stages of infection, individual motile (P -GFP-positive) and virulent (P - and P -GFP-positive) L.

Possible Prosthetic Valve Endocarditis by and Specific Virulence Mechanisms.

Bacteremia by spp. has rarely been described before. We report the first case of a possible prosthetic valve endocarditis, according to the modified Duke criteria, in a 37-year old male injecting drug user suffering from recurrent endocarditis.

Quorum sensing controls persistence, resuscitation, and virulence of Legionella subpopulations in biofilms.

The water-borne bacterium Legionella pneumophila is the causative agent of Legionnaires' disease. In the environment, the opportunistic pathogen colonizes different niches, including free-living protozoa and biofilms. The physiological state(s) of sessile Legionella in biofilms and their functional consequences are not well understood.

Keap1 governs ageing-induced protein aggregation in endothelial cells.

The breach of proteostasis, leading to the accumulation of protein aggregates, is a hallmark of ageing and age-associated disorders, up to now well-established in neurodegeneration. Few studies have addressed the issue of dysfunctional cell response to protein deposition also for the cardiovascular system. However, the molecular basis of proteostasis decline in vascular cells, as well as its relation to ageing, are not understood.

Mycobacterium marinum produces distinct mycobactin and carboxymycobactin siderophores to promote growth in broth and phagocytes.

Mycobacterium marinum is a model organism for pathogenic Mycobacterium species, including Mycobacterium tuberculosis, the causative agent of tuberculosis. These pathogens enter phagocytes and replicate within the Mycobacterium-containing vacuole, possibly followed by vacuole exit and growth in the host cell cytosol. Mycobacteria release siderophores called mycobactins to scavenge iron, an essential yet poorly soluble and available micronutrient.

Quorum sensing modulates the formation of virulent Legionella persisters within infected cells.

The facultative intracellular bacterium Legionella pneumophila replicates in environmental amoebae and in lung macrophages, and causes Legionnaires' disease. Here we show that L. pneumophila reversibly forms replicating and nonreplicating subpopulations of similar size within amoebae.

Keap1 controls protein S-nitrosation and apoptosis-senescence switch in endothelial cells.

Premature senescence, a death escaping pathway for cells experiencing stress, is conducive to aging and cardiovascular diseases. The molecular switch between senescent and apoptotic fate remains, however, poorly recognized. Nrf2 is an important transcription factor orchestrating adaptive response to cellular stress.

PIKfyve/Fab1 is required for efficient V-ATPase and hydrolase delivery to phagosomes, phagosomal killing, and restriction of Legionella infection.

By engulfing potentially harmful microbes, professional phagocytes are continually at risk from intracellular pathogens. To avoid becoming infected, the host must kill pathogens in the phagosome before they can escape or establish a survival niche. Here, we analyse the role of the phosphoinositide (PI) 5-kinase PIKfyve in phagosome maturation and killing, using the amoeba and model phagocyte Dictyostelium discoideum.

Single Cell Analysis of Legionella and Legionella-Infected Acanthamoeba by Agarose Embedment.

Legionella pneumophila resides in multispecies biofilms, where it infects and replicates in environmental protozoa such as Acanthamoeba castellanii. Studies on L. pneumophila physiology and host-pathogen interactions are frequently conducted using clonal bacterial populations and population level analysis, overlooking the remarkable differences in single cell behavior.

Legionella quorum sensing and its role in pathogen-host interactions.

Legionella pneumophila is a water-borne opportunistic pathogen causing a life-threatening pneumonia called 'Legionnaires' disease'. The Legionella quorum sensing (Lqs) system produces and responds to the α-hydroxyketone signaling molecule 3-hydroxypentadecane-4-one (Legionella autoinducer-1, LAI-1). The Lqs system controls the switch between the replicative/non-virulent and the transmissive/virulent phase of L.

ER remodeling by the large GTPase atlastin promotes vacuolar growth of .

The pathogenic bacterium replicates in host cells within a distinct ER-associated compartment termed the -containing vacuole (LCV). How the dynamic ER network contributes to pathogen proliferation within the nascent LCV remains elusive. A proteomic analysis of purified LCVs identified the ER tubule-resident large GTPase atlastin3 (Atl3, yeast Sey1p) and the reticulon protein Rtn4 as conserved LCV host components.

Subversion of Retrograde Trafficking by Translocated Pathogen Effectors.

Intracellular bacterial pathogens subvert the endocytic bactericidal pathway to form specific replication-permissive compartments termed pathogen vacuoles or inclusions. To this end, the pathogens employ type III or type IV secretion systems, which translocate dozens, if not hundreds, of different effector proteins into their host cells, where they manipulate vesicle trafficking and signaling pathways in favor of the intruders. While the distinct cocktail of effectors defines the specific processes by which a pathogen vacuole is formed, the different pathogens commonly target certain vesicle trafficking routes, including the endocytic or secretory pathway.

Phenotypic variation of Salmonella in host tissues delays eradication by antimicrobial chemotherapy.

Antibiotic therapy often fails to eliminate a fraction of transiently refractory bacteria, causing relapses and chronic infections. Multiple mechanisms can induce such persisters with high antimicrobial tolerance in vitro, but their in vivo relevance remains unclear. Using a fluorescent growth rate reporter, we detected extensive phenotypic variation of Salmonella in host tissues.

Regulated shift from helical to polar localization of Listeria monocytogenes cell wall-anchored proteins.

Many virulence factors of Gram-positive bacterial pathogens are covalently anchored to the peptidoglycan (PG) by sortase enzymes. However, for rod-shaped bacteria little is known about the spatiotemporal organization of these surface proteins in the cell wall. Here we report the three-dimensional (3D) localization of the PG-bound virulence factors InlA, InlH, InlJ, and SvpA in the envelope of Listeria monocytogenes under different growth conditions.

The stress-induced virulence protein InlH controls interleukin-6 production during murine listeriosis.

The genome of the pathogenic bacterium Listeria monocytogenes contains a family of genes encoding proteins with a leucine-rich repeat domain. One of these genes, inlH, is a sigma(B)-dependent virulence gene of unknown function. Previously, inlH was proposed to be coexpressed with two adjacent internalin genes, inlG and inlE.

The Listeria monocytogenes virulence factor InlJ is specifically expressed in vivo and behaves as an adhesin.

The food-borne pathogen Listeria monocytogenes is adapted to a diversity of environments, such as soil, food, body fluids, and the cytosol of eukaryotic cells. The transition between saprophytic and pathogenic life is mediated through complex regulatory pathways that modulate the expression of virulence factors. Here we examined the expression of inlJ, a recently identified gene encoding a protein of the LPXTG-internalin family and involved in pathogenesis.