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Pathogenicity and Virulence
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
While it is generally held that adherence is a prerequisite for infection and the production of disease, there are some situations in which this characteristic is detrimental to the microorganism. Study of urinary tract infections with Proteus in rats revealed that the presence of fimbriae was required for establishment of infection in the urinary tract, but that these same fimbriae enhanced phagocytosis of the organism when it entered the bloodstream. Those species that can undergo phase variation to suppress adhesins may therefore have a distinct survival advantage in systemic infections.
Urinary Tract Infection
Published in Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George, The Scientific Basis of Urology, 2010
The observations noted above might assist treatment of affected individuals in a number of ways. Variation in adhesion potential might identify at-risk groups. Fimbriae would appear to be a rational target for antimicrobial therapy and vaccine development. In the veterinary piglets experiment referred to above, effective vaccines based initially on the K-88 antigen were developed and successfully prevented neonatal diarrhea in the susceptible groups. Immunization with purified P fimbriae has been attempted in a number of animal models, with variable success. In a primate setting, vaccination with a FimH adhesin– chaperone complex protected three of four treated monkeys while all control animals developed cystitis, suggesting that such techniques might have application in humans with chronic lower UTI (68). As might be expected, phase variation and other types of antigen variability might be expected to cause problems in this type of therapeutic approach.
Neisseria gonorrhoeae
Published in Peter M. Lydyard, Michael F. Cole, John Holton, William L. Irving, Nino Porakishvili, Pradhib Venkatesan, Katherine N. Ward, Case Studies in Infectious Disease, 2010
Peter M. Lydyard, Michael F. Cole, John Holton, William L. Irving, Nino Porakishvili, Pradhib Venkatesan, Katherine N. Ward
The pilin (PilE) protein contains a constant N-terminal domain, a hyper-variable C-terminal domain, and several variable regions termed mini-cassettes, which are encoded by genes with varying DNA sequence. The gonococcus has a single complete copy of the pilin gene termed pilE but as many as 15 truncated genes with variable DNA sequence. The truncation is at the 5′ end, resulting in lack of the sequence encoding the N-terminal constant domain and promoter elements. These truncated genes are termed pilS (silent) and form the pilS locus. By recombination of pilS sequences into the pilE gene the bacterium can express a high number of antigenically distinct pili. In addition to antigenic variation the pili undergo phase variation. In phase variation the bacterium has the ability to turn pilus expression on or off at a high frequency.
Flagellum and toxin phase variation impacts intestinal colonization and disease development in a mouse model of Clostridioides difficile infection
Published in Gut Microbes, 2022
Dominika Trzilova, Mercedes A. H. Warren, Nicole C. Gadda, Caitlin L. Williams, Rita Tamayo
Many bacterial species employ phase variation to generate phenotypic heterogeneity within a clonal population. Bacteria frequently encounter selective pressures in their environment, and phenotypic heterogeneity helps ensure survival by creating subpopulations that are differentially equipped to overcome these pressures.1 Phase variation typically affects the production of surface factors that directly interface with the bacterium’s environment, such as flagella, pili, and exopolysaccharides. Both mucosal pathogens and commensal species employ phase variation to balance the fitness advantages conferred by these structures with the costs of producing them; in a host environment, the ability to phase vary can promote immune evasion and persistence in the host.2 Phase variation can be achieved by multiple epigenetic and genetic mechanisms, including DNA modification by methylation, slipped-strand mispairing, homologous recombination, and site-specific recombination.1,3
Promoter orientation of the immunomodulatory Bacteroides fragilis capsular polysaccharide A (PSA) is off in individuals with inflammatory bowel disease (IBD)
Published in Gut Microbes, 2019
Lucy E. Blandford, Emma L. Johnston, Jeremy D. Sanderson, William G. Wade, Alistair J. Lax
We describe here the first analysis of B. fragilis PSA promoter orientation from human samples, and their possible correlation with disease states. The analysis was conducted on DNA extracted from snap frozen samples, and therefore represents as closely as possible PSA promoter orientation in vivo. PSA promoter orientation has not previously been studied in human tissue samples. The nearest comparable research was carried out in fecal samples from various mouse models22, where it was found that in monocolonized mice after 9 weeks approximately 80% of B. fragilis has the PSA promoter orientated on, but, after 11 weeks, this value decreased towards ~50%. In the most comparable result from our study it was observed that in a healthy cohort there is a heterogeneous population of B. fragilis in terms of capsular polysaccharide. The percentage of B. fragilis with the PSA promoter orientated ON in healthy individuals had a median value of between 40% and 60% with a 95% C.I. (Figure 2). This concurs with a theory of the biological significance of phase variation, that it creates heterogeneity within a clonal population allowing for diversity to protect against sudden environmental stresses.23
The adhesins of non-typeable Haemophilus influenzae
Published in Expert Review of Anti-infective Therapy, 2018
Karen L. Osman, Johanna M. Jefferies, Christopher H. Woelk, David W. Cleary, Stuart C. Clarke
Despite the proposed role of HMW in colonization, HMW along with HIA display high levels of immunogenicity [31], but risk of immune evasion can be lowered by reducing the expression of these proteins. This is achieved by phase variation which results in an alteration to the promoter sequence of the genes. (Figure 1) [32–34]. HMW expression is reduced by the addition of 7bp tandem repeats inserted near the hmw promotor [33]. This results in a stepped reduction of the protein with each increase of repeat, and is reversible, resulting in strains of NTHi that can switch between a spectrum of colonization or immune evasion [34]. Similarly, a reduction in Hia is observed with an extension of a poly T tract again located near the promoter of the hia gene [32]. The size of the poly T tract correlates negatively with protein expression of HIA [32]. Although somewhat off topic for this review it is interesting to note also that HMW has been reported to have a supplementary role in auto immune disease [35]. Antibodies to hyperglucosylated HMW1A have been found in the sera of multiple sclerosis patients, indicating HMW as an exogenous agent that triggers an auto immune response in multiple sclerosis [35]. This exhibits the wide and varied roles of the adhesins found in H. influenzae in the aetiologies of different diseases.