Septins and Bacterial Infection

Septins, a unique cytoskeletal component associated with cellular membranes, are increasingly recognized as having important roles in host defense against bacterial infection. A role for septins during invasion of Listeria monocytogenes into host cells was first proposed in 2002. Since then, work has shown that septins assemble in response to a wide variety of invasive bacterial pathogens, and septin assemblies can have different roles during the bacterial infection process. Here we review the interplay between septins and bacterial pathogens, highlighting septins as a structural determinant of host defense. We also discuss how investigation of septin assembly in response to bacterial infection can yield insight into basic cellular processes including phagocytosis, autophagy, and mitochondrial dynamics

Shigella sonnei

Shigella sonnei is a rod-shaped, Gram-negative facultative intracellular pathogen. It was named ‘Sonne’s bacillus’ after Carl Olaf Sonne who described it as a causative agent of bacillary dysentery. S. sonnei is distributed worldwide and represents the most common cause of shigellosis in industrialized regions in Europe, North America, and Australia. It is currently undergoing expansion in middle-income countries across Asia, Latin America, and the Middle East. S. sonnei evolved from Escherichia coli to specialize in intracellular infection of the human gut epithelium, and its genome comprises a 4.99 Mbp circular chromosome and a 216 kbp invasion plasmid (pINV) required for virulence. The chromosome is ~6% smaller than other E. coli and is punctuated by >300 copies of insertion sequence (IS) elements, whose expansion has degraded the genome through disruption and deletion of genes. Here we describe the key and disease facts allowing bacteria to evade host immune defences and to establish infection

Diversity-generating machines: genetics of bacterial sugar-coating

Bacterial pathogens and commensals are surrounded by diverse surface polysaccharides which include capsules and lipopolysaccharides. These carbohydrates play a vital role in bacterial ecology and interactions with the environment. Here, we review recent rapid advancements in this field, which have improved our understanding of the roles, structures, and genetics of bacterial polysaccharide antigens. Genetic loci encoding the biosynthesis of these antigens may have evolved as bacterial diversity-generating machines, driven by selection from a variety of forces, including host immunity, bacteriophages, and cell-cell interactions. We argue that the high adaptive potential of polysaccharide antigens should be taken into account in the design of polysaccharide-targeting medical interventions like conjugate vaccines and phage-based therapies

Autophagy and bacterial clearance: a not so clear picture.

Autophagy, an intracellular degradation process highly conserved from yeast to humans, is viewed as an important defence mechanism to clear intracellular bacteria. However, recent work has shown that autophagy may have different roles during different bacterial infections that restrict bacterial replication (antibacterial autophagy), act in cell autonomous signalling (non-bacterial autophagy) or support bacterial replication (pro-bacterial autophagy). This review will focus on newfound interactions of autophagy and pathogenic bacteria, highlighting that, in addition to delivering bacteria to the lysosome, autophagy responding to bacterial invasion may have a much broader role in mediating disease outcome

Distribution of Demersal Fishes on Unconsolidated Bottom Habitat of the Northern Gulf of Mexico

Benthic habitat on the continental shelf in the northern Gulf of Mexico (NGoM) is dominated by large plains of unconsolidated terrigenous sediment. This unconsolidated bottom habitat (UBH) is presumed to be sparsely inhabited by demersal fishes, and little is known about the factors that structure the distribution and abundance of fishes on UBH. In this study, an integrated acoustic/video approach was employed to quantify the distribution of demersal fishes on UBH across the continental shelf off Texas. Split-beam echo sounder surveys were paired with simultaneous video from imaging sonar and standard cameras to determine the occurrence and density of demersal fishes on UBH. The relative performances of the different gear types at detecting and enumerating both demersal fishes and bottom relief anomalies were compared. Occurrence (presence/absence) and density of demersal fishes was then related to a suite of habitat and environmental variables using generalized additive models (GAMs) to identify the variables that contribute to the quality of UBH used by demersal fishes. Standard camera video performed poorly for detection and enumeration of demersal fishes as well as bottom relief anomalies associated with UBH due to the persistent nepheloid layer at all locations surveyed. Echo sounder and imaging sonar surveys showed similar performances in detecting fishes and relief anomalies, but their performance varied in enumerating both variables. GAMs constructed from the echo sounder dataset indicated that a shallow depth, high percent coverage and large size of relief anomalies, low salinity, warmer temperature and closer proximity to non-platform artificial structure positively influenced the quality of UBH for demersal fishes. Close proximity to active petroleum platforms had a slight negative influence. The results of this study provide insight into the factors that regulate the distribution and abundance of demersal fishes in the NGoM, and the methodological refinements developed here will guide future efforts to characterize populations of demersal fishes on UBH

Bacterial cell division is recognized by the septin cytoskeleton for restriction by autophagy.

Septins are cytoskeletal proteins widely recognized for their role in eukaryotic cell division. Septins also assemble into cage-like structures that entrap cytosolic Shigella flexneri targeted to macroautophagy/autophagy. Although the Shigella septin cage was discovered ~10 y ago, how septins recognize Shigella was poorly understood. We found that septins are recruited to regions of micrometer-scale curvature presented by dividing bacterial cells, and cardiolipin (a curvature-specific phospholipid) promotes septin recruitment to these regions. Chemical manipulation of bacteria revealed that following recruitment, septins assemble into cages around growing bacterial cells. Once assembled, septin cages inhibit Shigella cell division by autophagy and fusion with lysosomes. Thus, recognition of dividing bacterial cells by the septin cytoskeleton targets intracellular pathogens to antibacterial autophagy

The history of septin biology and bacterial infection.

Investigation of cytoskeleton during bacterial infection has significantly contributed to both cell and infection biology. Bacterial pathogens Listeria monocytogenes and Shigella flexneri are widely recognised as paradigms for investigation of the cytoskeleton during bacterial entry, actin-based motility, and cell-autonomous immunity. At the turn of the century, septins were a poorly understood component of the cytoskeleton mostly studied in the context of yeast cell division and human cancer. In 2002, a screen performed in the laboratory of Pascale Cossart identified septin family member MSF (MLL septin-like fusion, now called SEPT9) associated with L. monocytogenes entry into human epithelial cells. These findings inspired the investigation of septins during L. monocytogenes and S. flexneri infection at the Institut Pasteur, illuminating important roles for septins in host-microbe interactions. In this review, we revisit the history of septin biology and bacterial infection, and discuss how the comparative study of L. monocytogenes and S. flexneri has been instrumental to understand septin roles in cellular homeostasis and host defence