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The cell envelope is the first line of defense between a bacterium and the world-at-large. Often, the initial steps that determine the outcome of chemical warfare, bacteriophage infections, and battles with other bacteria or the immune system greatly depend on the structure and composition of the bacterial cell surface. One of the most studied bacterial surface molecules is the glycolipid known as lipopolysaccharide (LPS), which is produced by most Gram-negative bacteria. Much of the initial attention LPS received in the early 1900s was owed to its ability to stimulate the immune system, for which the glycolipid was commonly known as endotoxin. It was later discovered that LPS also creates a permeability barrier at the cell surface and is a main contributor to the innate resistance that Gram-negative bacteria display against many antimicrobials. Not surprisingly, these important properties of LPS have driven a vast and still prolific body of literature for more than a hundred years. LPS research has also led to pioneering studies in bacterial envelope biogenesis and physiology, mostly using Escherichia coli and Salmonella as model systems. In this review, we will focus on the fundamental knowledge we have gained from studies of the complex structure of the LPS molecule and the biochemical pathways for its synthesis, as well as the transport of LPS across the bacterial envelope and its assembly at the cell surface.

The F plasmid or F-factor is a large, 100-kbp, circular conjugative plasmid of Escherichia coli and was originally described as a vector for horizontal gene transfer and gene recombination in the late 1940s. Since then, F and related F-like plasmids have served as role models for bacterial conjugation. At present, more than 200 different F-like plasmids with highly related DNA transfer genes, including those for the assembly of a type IV secretion apparatus, are completely sequenced. They belong to the phylogenetically related MOB_F12A group. F-like plasmids are present in enterobacterial hosts isolated from clinical as well as environmental samples all over the world. As conjugative plasmids, F-like plasmids carry genetic modules enabling plasmid replication, stable maintenance, and DNA transfer. In this plasmid backbone of approximately 60 kbp, the DNA transfer genes occupy the largest and mostly conserved part. Subgroups of MOB_F12A plasmids can be defined based on the similarity of TraJ, a protein required for DNA transfer gene expression. In addition, F-like plasmids harbor accessory cargo genes, frequently embedded within transposons and/or integrons, which harness their host bacteria with antibiotic resistance and virulence genes, causing increasingly severe problems for the treatment of infectious diseases. Here, I focus on key genetic elements and their encoded proteins present on the F-factor and other typical F-like plasmids belonging to the MOB_F12A group of conjugative plasmids.

The biogenesis of periplasmic and outer membrane proteins (OMPs) in Escherichia coli is assisted by a variety of processes that help with their folding and transport to their final destination in the cellular envelope. Chaperones are macromolecules, usually proteins, that facilitate the folding of proteins or prevent their aggregation without becoming part of the protein's final structure. Because chaperones often bind to folding intermediates, they often (but not always) act to slow protein folding. Protein folding catalysts, on the other hand, act to accelerate specific steps in the protein folding pathway, including disulfide bond formation and peptidyl prolyl isomerization. This review is primarily concerned with E. coli and Salmonella periplasmic and cellular envelope chaperones; it also discusses periplasmic proline isomerization.

Extraintestinal pathogenic Escherichia coli (ExPEC) are important pathogens in humans and certain animals. Molecular epidemiological analyses of ExPEC are based on structured observations of E. coli strains as they occur in the wild. By assessing real-world phenomena as they occur in authentic contexts and hosts, they provide an important complement to experimental assessment. Fundamental to the success of molecular epidemiological studies are the careful selection of subjects and the use of appropriate typing methods and statistical analysis. To date, molecular epidemiological studies have yielded numerous important insights into putative virulence factors, host-pathogen relationships, phylogenetic background, reservoirs, antimicrobial-resistant strains, clinical diagnostics, and transmission pathways of ExPEC, and have delineated areas in which further study is needed. The rapid pace of discovery of new putative virulence factors and the increasing awareness of the importance of virulence factor regulation, expression, and molecular variation should stimulate many future molecular epidemiological investigations. The growing sophistication and availability of molecular typing methodologies, and of the new computational and statistical approaches that are being developed to address the huge amounts of data that whole genome sequencing generates, provide improved tools for such studies and allow new questions to be addressed.

Gram-negative bacteria assemble a variety of surface structures, including the hair-like organelles known as pili or fimbriae. Pili typically function in adhesion and mediate interactions with various surfaces, with other bacteria, and with other types of cells such as host cells. The chaperone/usher (CU) pathway assembles a widespread class of adhesive and virulence-associated pili. Pilus biogenesis by the CU pathway requires a dedicated periplasmic chaperone and integral outer membrane protein termed the usher, which forms a multifunctional assembly and secretion platform. This review addresses the molecular and biochemical aspects of the CU pathway in detail, focusing on the type 1 and P pili expressed by uropathogenic Escherichia coli as model systems. We provide an overview of representative CU pili expressed by E. coli and Salmonella, and conclude with a discussion of potential approaches to develop antivirulence therapeutics that interfere with pilus assembly or function.

Proteus mirabilis, a Gram-negative rod-shaped bacterium most noted for its swarming motility and urease activity, frequently causes catheter-associated urinary tract infections (CAUTIs) that are often polymicrobial. These infections may be accompanied by urolithiasis, the development of bladder or kidney stones due to alkalinization of urine from urease-catalyzed urea hydrolysis. Adherence of the bacterium to epithelial and catheter surfaces is mediated by 17 different fimbriae, most notably MR/P fimbriae. Repressors of motility are often encoded by these fimbrial operons. Motility is mediated by flagella encoded on a single contiguous 54-kb chromosomal sequence. On agar plates, P. mirabilis undergoes a morphological conversion to a filamentous swarmer cell expressing hundreds of flagella. When swarms from different strains meet, a line of demarcation, a "Dienes line," develops due to the killing action of each strain's type VI secretion system. During infection, histological damage is caused by cytotoxins including hemolysin and a variety of proteases, some autotransported. The pathogenesis of infection, including assessment of individual genes or global screens for virulence or fitness factors has been assessed in murine models of ascending urinary tract infections or CAUTIs using both single-species and polymicrobial models. Global gene expression studies performed in culture and in the murine model have revealed the unique metabolism of this bacterium. Vaccines, using MR/P fimbria and its adhesin, MrpH, have been shown to be efficacious in the murine model. A comprehensive review of factors associated with urinary tract infection is presented, encompassing both historical perspectives and current advances.

The history of Shigella, the causative agent of bacillary dysentery, is a long and fascinating one. This brief historical account starts with descriptions of the disease and its impact on human health from ancient time to the present. Our story of the bacterium starts just before the identification of the dysentery bacillus by Kiyoshi Shiga in 1898 and follows the scientific discoveries and principal scientists who contributed to the elucidation of Shigella pathogenesis in the first 100 years. Over the past century, Shigella has proved to be an outstanding model of an invasive bacterial pathogen and has served as a paradigm for the study of other bacterial pathogens. In addition to invasion of epithelial cells, some of those shared virulence traits include toxin production, multiple-antibiotic resistance, virulence genes encoded on plasmids and bacteriophages, global regulation of virulence genes, pathogenicity islands, intracellular motility, remodeling of host cytoskeleton, inflammation/polymorphonuclear leukocyte signaling, apoptosis induction/inhibition, and "black holes" and antivirulence genes. While there is still much to learn from studying Shigella pathogenesis, what we have learned so far has also contributed greatly to our broader understanding of bacterial pathogenesis.

In Escherichia coli, proteins found in the periplasm or the outer membrane are exported from the cytoplasm by the general secretory, Sec, system before they acquire stably folded structure. This dynamic process involves intricate interactions among cytoplasmic and membrane proteins, both peripheral and integral, as well as lipids. In vivo, both ATP hydrolysis and proton motive force are required. Here, we review the Sec system from the inception of the field through early 2016, including biochemical, genetic, and structural data.