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The gastrointestinal system
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Sharon J. White, Francis A. Carey
Gastric mucosal colonization by H. pylori and the consequent superficial active chronic gastritis are not necessarily (or even commonly) associated with clinical disease. In the absence of ulceration there is a very poor correlation between infection and dyspeptic symptoms. Infection is, however, associated, with varying degrees of certainty, with a number of important conditions, ranging from peptic ulceration to atrophic gastritis, adenocarcinoma, and lymphoma (Figure 10.25). There is also an epidemiological link with extraintestinal disease such as abnormally short stature and ischaemic heart disease, although the link in these instances is unlikely to be causal. The ability of H. pylori to cause disease is dependent (as in many chronic infectious diseases) on both bacterial virulence factors and variations in host response. Studies of mutant organisms have shown that bacterial motility and urease activity are essential for survival. The organism also produces adhesion factors, including a haemagglutinin that binds to sugar moieties on the gastric epithelial cell membrane. Virulent strains have also been shown to produce a number of tissue-injuring factors, including Gram-negative lipopolysaccharide and the highly antigenic CagA and VacA proteins, as well as a number of heat shock proteins. The host cell response (polymorph leukocytes, lymphocytes, and plasma cells) is characterized by high levels of proinflammatory cytokines including IL-1, IL-8, and TNF-α. Cytokine production is thought to be important in the increased gastrin secretion seen in H. pylori gastritis. Other physiological changes have been identified, including an increased gastrin response to infused gastrin-releasing peptide (GRP). These changes are most marked in patients with duodenal ulceration. Some individuals show a tendency to low gastric acid output, and these tend to develop a severe pangastritis, gastric ulceration, and possibly adenocarcinoma.
Microbial Biofilms
Published in Chaminda Jayampath Seneviratne, Microbial Biofilms, 2017
Chaminda Jayampath Seneviratne, Neha Srivastava, Intekhab Islam, Kelvin Foong and Finbarr Allen
The critical question that needs to be addressed is the trigger that makes a bacterium adhere to a particular surface, abandoning its free-floating or ‘planktonic’ mode of growth. Although contact with a surface is a primary requisite, not all bacteria in close proximity to a surface adhere to it. The properties of the surfaces and their interactions with the bacteria play a major role in the initial attachment phase. Microorganisms can come into contact with a given surface by means of Brownian motion, sedimentation, movement with liquid flow, bacterial motility conferred by cell surface appendages or by travelling with other cells as aggregates [17]. A bacterium in liquid without any means of active locomotion will move as a result of random collisions with its surrounding molecules. Random walks describe the trajectory of a particle that steps in any direction in space with equal probability per unit time [18]. These random movements are called diffusion or Brownian motion. Bacterial surface appendages such as type IV pili (TFP) facilitate surface sensing by the bacterium, allowing it to transit from vertical into horizontal cell orientation such as seen in Pseudomonas aeruginosa [18]. The net interactions occurring as a result of these motions or surface appendages determine the course of attachment of the microbe to the surface. For example, it is suggested that a low level of TFP production primes planktonic microorganisms to use their pili to ‘feel’ the surface [19]. Once attached to the surface, TFP helps microbes to ‘crawl’ when the surface is oriented parallel to the cell and ‘walk’ when the cell is in upright position [20]. However, adhesion mediated by TFP seems to be unspecific, as it allows the bacterium to adhere to almost all known abiotic and biotic surfaces [18]. The critical proximity distance determining microbial attachment to a surface is less than 1 nm. At this proximity, the net sum of attractive and repulsive forces determines the adhesion process. These include electrostatic and hydrophobic interactions, steric hindrance, van der Waals forces, temperature and hydrodynamic forces. Though bacterial surfaces are negatively charged in general [21], surface charges may become irrelevant in the case of dead cells among floating bacterial communities, as they may change their coadhesion properties. For example, bacteria swimming in close proximity to surfaces experience hydrodynamic forces that both attract them towards the surface and cause them to move in circular trajectories [22].
Recent advances in lipopolysaccharide-based glycoconjugate vaccines
Published in Expert Review of Vaccines, 2021
Henderson Zhu, Christine S. Rollier, Andrew J. Pollard
In many instances, antibodies targeting LPS confer protection against bacterial infections. In vitro studies showed antibodies to the O-Ag (O-SP and the core oligosaccharide) induced protection against Klebsiella pneumoniae, Vibrio cholerae, N. meningitidis, and Salmonella enterica by mediating opsonophagocytosis, complement-mediated lysis, and agglutination [37–40]. It has been recently shown that anti-LPS IgG within the mucus layer of the gastrointestinal mucosa can crosslink with mucin to capture S. Typhimurium on the mucin mesh, thus inhibiting the flagellum-based bacterial motility [41]. This capturing of bacteria highlighted a new, but potentially conserved mechanism of protection, likely involved in the protection against other enteric pathogens. The neutralizing effect of the O-Ag-specific antibodies is weaker in encapsulated bacteria, such as encapsulated serotypes of Klebsiella pneumoniae, because the shielding created by CPS can lower the accessibility of anti-LPS antibodies to the LPS [42].
Insights into coumarin-mediated inhibition of biofilm formation in Salmonella Typhimurium
Published in Biofouling, 2020
Samriddhi Thakur, Semanti Ray, Siddharth Jhunjhunwala, Dipankar Nandi
Since bacterial motility is inherently linked to biofilm formation in bacteria (Ray et al. 2020), the effects of coumarin on the two major types of flagellar motility, swimming and swarming were investigated. As seen in Figure 3(A), coumarin hindered swimming motility initially (6 h), and the effect persisted for a period of time (12 h). However, by the end of the incubation period at 24 h, this retardation in swimming motility was alleviated. Swimming motility did not recover completely when coumarin was used at the highest dose (5 mM), possibly due to the partial lethality of this dose (Figure 3(A, i and ii)). Swarming motility, on the other hand, showed significant abrogation even at 2.5 mM at earlier (12 h) and later time points (18 and 24 h). At 5 mM coumarin, swarming motility was completely abrogated (Figure 3(B, i and ii)).
Micro-nanorobots: important considerations when developing novel drug delivery platforms
Published in Expert Opinion on Drug Delivery, 2019
Ajay Vikram Singh, Mohammad Hasan Dad Ansari, Peter Laux, Andreas Luch
More downstream challenges arise, as robust protocols are developed to attach these self-propelled biological cells, enhancing longevity of cell-micro/nano component and uncontrolled proliferation of biological cells attached to propel the robots. Adhering biological cells to power the microrobots needs engineering pervasive to head on attachment to propel the microrobots with maximum torque to achieve a maximum propulsion speed [54]. The longevity of biological bonds can be achieved with covalent modifications and rendering to maneuver for longer durations. However, new method devices will always make the field better for TDD. The biological cells with a short doubling time (E. coli doubling time 45 minutes, microalgae C. reinhardtii 4–5 hours) further populate the drug delivery site via continuous proliferation, and may cause infections in case of bacteria-propelled robots. Propulsion media inhibiting growth of such microswimmer are following challenges for such biohybrid designs for the TDD. A bacterial motility medium has been formulated which checks the growth. However, studies that are more systematic are needed to decode the influence of such a medium on bacterial flagellar motor smooth navigation and on/off cycle control.