Cellular microbiology

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Salmonella bacteria (red) invade cultured human cells SalmonellaNIAID.jpg
Salmonella bacteria (red) invade cultured human cells

Cellular microbiology is a discipline that bridges microbiology and cell biology.

The term "cellular microbiology" was coined by the authors of the book of the same title published in 1996. [1] Cooperation and mutual dependency between microbiology and cell biology had been increasing in the years before that, and the emergence of a new discipline had been suggested and discussed in several scientific conferences.

Cellular microbiology attempts to use pathogenic microorganisms as tools for cell-biology research, and to employ cell-biology methods to understand the pathogenicity of microorganisms. Toxins and virulence factors from microbes have been used for decades to influence processes in eukaryotic cells and to study them. It has increasingly appeared that applying a purified toxin on a cell does not always provide the complete picture, and that understanding the role of the toxin in pathogenicity, the way the toxin promotes the microbe, the way the toxin is produced and the co-evolution of the toxin and its host-cell counterparts, is crucial.

Numerous eukaryotic cellular processes have been clarified using microbial "tools". A major subject in this category is the cytoskeleton. Many microbes modify and influence the synthesis or degradation of the host-cell cytoskeleton, in particular the actin network. [2] Intracellular microbes, such as the bacteria Salmonella and Shigella , elicit actin polymerization in host cells that otherwise do not internalize microbes (non-phagocytes). This causes the formation of projections that eventually engulf the bacteria. Bacteria such as Yersinia inhibit actin polymerization in phagocytes, thereby preventing their uptake. Cellular microbiology tries to understand these processes and how they promote infection. Other eukaryotic processes that microbes influence and that are researched using microbes are signal transduction, metabolism, vesicle trafficking, cell cycle and transcriptional regulation, to name but a few.

Recently, the field of Cellular Microbiology has been expanded to incorporate investigation of the cell biology of microbes themselves. [3] [4] "The field of cellular microbiology is a coalescence of two fields: molecular microbiology and cell biology," said Professor Jacek Hawiger, Chair of Microbiology and Immunology at Vanderbilt University. [4] Particularly in the case of bacterial cells, new technology is starting to be used to reveal a high level of organization within the bacterial cells themselves. For example, high-resolution fluorescence microscopy [5] and atomic force microscopy [6] are both being used to show just how sophisticated bacterial cells are.

Related Research Articles

<span class="mw-page-title-main">Cytoskeleton</span> Network of filamentous proteins that forms the internal framework of cells

The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is composed of similar proteins in the various organisms. It is composed of three main components:microfilaments, intermediate filaments, and microtubules, and these are all capable of rapid growth or disassembly depending on the cell's requirements.

<span class="mw-page-title-main">Actin</span> Family of proteins

Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over 100 μM; its mass is roughly 42 kDa, with a diameter of 4 to 7 nm.

<i>Listeria monocytogenes</i> Species of pathogenic bacteria that causes the infection listeriosis

Listeria monocytogenes is the species of pathogenic bacteria that causes the infection listeriosis. It is a facultative anaerobic bacterium, capable of surviving in the presence or absence of oxygen. It can grow and reproduce inside the host's cells and is one of the most virulent foodborne pathogens: 20 to 30% of foodborne listeriosis infections in high-risk individuals may be fatal. In the European Union, listeriosis follows an upward trend that began in 2008, causing 2,161 confirmed cases and 210 reported deaths in 2014, 16% more than in 2013. Listeriosis mortality rates are also higher in the EU than for other foodborne pathogens. Responsible for an estimated 1,600 illnesses and 260 deaths in the United States annually, listeriosis ranks third in total number of deaths among foodborne bacterial pathogens, with fatality rates exceeding even Salmonella spp. and Clostridium botulinum.

<span class="mw-page-title-main">Phagosome</span>

In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs).

The bacterium, despite its simplicity, contains a well-developed cell structure which is responsible for some of its unique biological structures and pathogenicity. Many structural features are unique to bacteria and are not found among archaea or eukaryotes. Because of the simplicity of bacteria relative to larger organisms and the ease with which they can be manipulated experimentally, the cell structure of bacteria has been well studied, revealing many biochemical principles that have been subsequently applied to other organisms.

<span class="mw-page-title-main">Protein filament</span> Long chain of protein monomers

In biology, a protein filament is a long chain of protein monomers, such as those found in hair, muscle, or in flagella. Protein filaments form together to make the cytoskeleton of the cell. They are often bundled together to provide support, strength, and rigidity to the cell. When the filaments are packed up together, they are able to form three different cellular parts. The three major classes of protein filaments that make up the cytoskeleton include: actin filaments, microtubules and intermediate filaments.

Cytolysin refers to the substance secreted by microorganisms, plants or animals that is specifically toxic to individual cells, in many cases causing their dissolution through lysis. Cytolysins that have a specific action for certain cells are named accordingly. For instance, the cytolysins responsible for the destruction of red blood cells, thereby liberating hemoglobins, are named hemolysins, and so on. Cytolysins may be involved in immunity as well as in venoms.

Septins are a group of GTP-binding proteins expressed in all eukaryotic cells except plants. Different septins form protein complexes with each other. These complexes can further assemble into filaments, rings and gauzes. Assembled as such, septins function in cells by localizing other proteins, either by providing a scaffold to which proteins can attach, or by forming a barrier preventing the diffusion of molecules from one compartment of the cell to another, or in the cell cortex as a barrier to the diffusion of membrane-bound proteins.

The Rho family of GTPases is a family of small signaling G proteins, and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic kingdoms, including yeasts and some plants. Three members of the family have been studied in detail: Cdc42, Rac1, and RhoA. All G proteins are "molecular switches", and Rho proteins play a role in organelle development, cytoskeletal dynamics, cell movement, and other common cellular functions.

<span class="mw-page-title-main">Prokaryotic cytoskeleton</span> Structural filaments in prokaryotes

The prokaryotic cytoskeleton is the collective name for all structural filaments in prokaryotes. It was once thought that prokaryotic cells did not possess cytoskeletons, but advances in visualization technology and structure determination led to the discovery of filaments in these cells in the early 1990s. Not only have analogues for all major cytoskeletal proteins in eukaryotes been found in prokaryotes, cytoskeletal proteins with no known eukaryotic homologues have also been discovered. Cytoskeletal elements play essential roles in cell division, protection, shape determination, and polarity determination in various prokaryotes.

<span class="mw-page-title-main">Pathogenic bacteria</span> Disease-causing bacteria

Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and are often beneficial but others can cause infectious diseases. The number of these pathogenic species in humans is estimated to be fewer than a hundred. By contrast, several thousand species are part of the gut flora present in the digestive tract.

<span class="mw-page-title-main">Prokaryote</span> Unicellular organism that lacks a membrane-bound nucleus

A prokaryote is a single-cell organism whose cell lacks a nucleus and other membrane-bound organelles. The word prokaryote comes from the Ancient Greek πρό 'before' and κάρυον 'nut, kernel'. In the two-empire system arising from the work of Édouard Chatton, prokaryotes were classified within the empire Prokaryota. But in the three-domain system, based upon molecular analysis, prokaryotes are divided into two domains: Bacteria and Archaea. Organisms with nuclei are placed in a third domain, Eukaryota.

<span class="mw-page-title-main">Clostridium difficile toxin A</span>

Clostridium difficile toxin A (TcdA) is a toxin generated by Clostridioides difficile, formerly known as Clostridium difficile. It is similar to Clostridium difficile Toxin B. The toxins are the main virulence factors produced by the gram positive, anaerobic, Clostridioides difficile bacteria. The toxins function by damaging the intestinal mucosa and cause the symptoms of C. difficile infection, including pseudomembranous colitis.

<span class="mw-page-title-main">Microbiology</span> Study of microscopic organisms

Microbiology is the scientific study of microorganisms, those being of unicellular (single-celled), multicellular, or acellular. Microbiology encompasses numerous sub-disciplines including virology, bacteriology, protistology, mycology, immunology, and parasitology.

<span class="mw-page-title-main">Actin assembly-inducing protein</span>

The Actin assembly-inducing protein (ActA) is a protein encoded and used by Listeria monocytogenes to propel itself through a mammalian host cell. ActA is a bacterial surface protein comprising a membrane-spanning region. In a mammalian cell the bacterial ActA interacts with the Arp2/3 complex and actin monomers to induce actin polymerization on the bacterial surface generating an actin comet tail. The gene encoding ActA is named actA or prtB.

The Selman A. Waksman Award in Microbiology is awarded by the U.S. National Academy of Sciences "in recognition of excellence in the field of microbiology." Named after Selman Waksman, it was first awarded in 1968. A $5000 prize is included in the honor.

<span class="mw-page-title-main">Arp2/3 complex</span> Macromolecular complex

Arp2/3 complex is a seven-subunit protein complex that plays a major role in the regulation of the actin cytoskeleton. It is a major component of the actin cytoskeleton and is found in most actin cytoskeleton-containing eukaryotic cells. Two of its subunits, the Actin-Related Proteins ARP2 and ARP3, closely resemble the structure of monomeric actin and serve as nucleation sites for new actin filaments. The complex binds to the sides of existing ("mother") filaments and initiates growth of a new ("daughter") filament at a distinctive 70 degree angle from the mother. Branched actin networks are created as a result of this nucleation of new filaments. The regulation of rearrangements of the actin cytoskeleton is important for processes like cell locomotion, phagocytosis, and intracellular motility of lipid vesicles.

Paracytophagy is the cellular process whereby a cell engulfs a protrusion which extends from a neighboring cell. This protrusion may contain material which is actively transferred between the cells. The process of paracytophagy was first described as a crucial step during cell-to-cell spread of the intracellular bacterial pathogen Listeria monocytogenes, and is also commonly observed in Shigella flexneri. Paracytophagy allows these intracellular pathogens to spread directly from cell to cell, thus escaping immune detection and destruction. Studies of this process have contributed significantly to our understanding of the role of the actin cytoskeleton in eukaryotic cells.

The host–pathogen interaction is defined as how microbes or viruses sustain themselves within host organisms on a molecular, cellular, organismal or population level. This term is most commonly used to refer to disease-causing microorganisms although they may not cause illness in all hosts. Because of this, the definition has been expanded to how known pathogens survive within their host, whether they cause disease or not.

The type VI secretion system (T6SS) is molecular machine used by a wide range of Gram-negative bacterial species to transport effectors from the interior of a bacterial cell across the cellular envelope into an adjacent target cell. While often reported that the T6SS was discovered in 2006 by researchers studying the causative agent of cholera, Vibrio cholerae, the first study demonstrating that T6SS genes encode a protein export apparatus was actually published in 2004, in a study of protein secretion by the fish pathogen Edwardsiella tarda.

References

  1. Cossart, P.; Boquet, P.; Normark, S.; Rappuoli, R. (1996). "Cellular Microbiology Emerging". Science. 271 (5247): 315–316. Bibcode:1996Sci...271..315C. doi:10.1126/science.271.5247.315. PMID   8553065. S2CID   32437757.
  2. Dramsi S, Cossart P (1998). "Intracellular pathogens and the actin cytoskeleton". Annu Rev Cell Dev Biol. 14 (1): 137–166. doi:10.1146/annurev.cellbio.14.1.137. PMID   9891781.
  3. NHMRC Program in Cellular Microbiology (http://cellularmicrobiologyprogram.org.au/ Archived 2019-05-03 at the Wayback Machine )
  4. 1 2 NIH Cellular and Molecular Microbiology (CMM) training program (http://www.mc.vanderbilt.edu/reporter/index.html?ID=988)
  5. Ebersbach, G; Jacobs-Wagner, C (Mar 2007). "Exploration into the spatial and temporal mechanisms of bacterial polarity". Trends Microbiol. 15 (3): 101–8. doi:10.1016/j.tim.2007.01.004. PMID   17275310.
  6. Dufrêne, YF (Sep 2008). "Towards nanomicrobiology using atomic force microscopy". Nat Rev Microbiol. 6 (9): 674–80. doi:10.1038/nrmicro1948. PMID   18622407. S2CID   1525798.