Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a food-borne pathogen that causes hemorrhagic colitis and the hemolytic uremic syndrome. Colonization of the human gut mucosa and production of potent Shiga toxins are critical virulence traits of EHEC. Although EHEC O157:H7 contains numerous putative pili operons, their role in the colonization of the natural bovine or accidental human hosts remains largely unknown. We have identified in EHEC an adherence factor, herein called E. coli common pilus (ECP), composed of a 21-kDa pilin subunit whose amino acid sequence corresponds to the product of the yagZ (renamed ecpA) gene present in all E. coli genomes sequenced to date. ECP production was demonstrated in 121 (71.6%) of a total of 169 ecpA ؉ strains representing intestinal and extraintestinal pathogenic as well as normal flora E. coli. High-resolution ultrastructural and immunofluorescence studies demonstrated the presence of abundant peritrichous fibrillar structures emanating from the bacterial surface forming physical bridges between bacteria adhering to cultured epithelial cells. Isogenic ecpA mutants of EHEC O157:H7 or fecal commensal E. coli showed significant reduction in adherence to cultured epithelial cells. Our data suggest that ECP production is a common feature of E. coli colonizing the human gut or other host tissues. ECP is a pilus of EHEC O157:H7 with a potential role in host epithelial cell colonization and may represent a mechanism of adherence of both pathogenic and commensal E. coli.pili ͉ enterohemorrhagic Escherichia coli ͉ normal flora
Commensal bacteria comprise a large part of the microbial world, playing important roles in human development, health and disease. However, little is known about the genomic content of commensals or how related they are to their pathogenic counterparts. The genus Neisseria, containing both commensal and pathogenic species, provides an excellent opportunity to study these issues. We undertook a comprehensive sequencing and analysis of human commensal and pathogenic Neisseria genomes. Commensals have an extensive repertoire of virulence alleles, a large fraction of which has been exchanged among Neisseria species. Commensals also have the genetic capacity to donate DNA to, and take up DNA from, other Neisseria. Our findings strongly suggest that commensal Neisseria serve as reservoirs of virulence alleles, and that they engage extensively in genetic exchange.
Highlights d Commensal Neisseria kill STD pathogen N. gonorrhoeae by releasing DNA into the environment d Killing requires DNA entry and recombination and a foreign DNA methylation pattern d Commensal N. elongata accelerates clearance of N. gonorrhoeae from the mouse vagina d A N. gonorrhoeae DNA uptake mutant resists this clearance
SummaryBrucella is an invasive organism that multiplies and survives within eukaryotic cells. The brucellae are able to adhere to the surface of cultured epithelial cells, a mechanism that may facilitate penetration and dissemination to other host tissues. However, no adhesins that allow the bacteria to interact with the surface of epithelial cells before migration within polymorphonuclear leukocytes, monocytes and macrophages have been described. Here, we show that Brucella surface proteins (SPs) with apparent molecular masses of 14, 18 and 41 kDa bound selectively to HeLa cells. However, only antibodies directed against the 41 kDa surface protein (SP41) inhibited in doseresponse manner, bacterial adherence and invasion of HeLa cells. HeLa cells treated with neuraminidase did not bind SP41, suggesting the involvement of cellular sialic acid residues in this interaction. Biochemical analysis of SP41 revealed that this protein is the predicted product of the ugpB locus, which showed significant homology to the glycerol-3-phosphatebinding ATP-binding cassette (ABC) transporter protein found in several bacterial species. SP41 appears to be exposed on the bacterial surface as determined by immunofluorescence and immunogold labelling with anti-SP41 antibody. An isogenic D ugpB mutant showed a significant inhibitory effect on Brucella adherence and invasion of human cultured epithelial cells and this effect could be reversed by restoration of the ugpB on a plasmid. Lastly, we also show that most of the sera from individuals with acute brucellosis, but not sera obtained from healthy donors or patients with chronic brucellosis, mount antibody reactivity against SP41, suggesting that this protein is produced in vivo and that it elicits an antibody immune response. These data are novel findings that offer new insights into understanding the interplay between this bacterium and host target cells, and identify a new target for vaccine development and prevention of brucellosis.
The genome of Vibrio cholerae contains five flagellin genes that encode proteins (FlaA-E) of 39 -41 kDa with 61-82% identity among them. Although the existing live oral attenuated vaccine strains against cholera are protective in humans, there is an intrinsic residual cytotoxic and inflammatory component associated with these candidate vaccine strains. Bacterial flagellins are known to be potent inducers of proinflammatory molecules via activation of Toll-like receptor 5. Here we found that purified flagella from wild type V. cholerae 395 induced significant release of interleukin (IL)-8 from cultured HT-29 human colonic epithelial cells. Furthermore we found that filtered supernatants of KKV90, a ⌬flaA isogenic strain unable to produce flagella, were still able to activate production of IL-8 albeit to significantly lower levels than the wild type, suggesting that other activators of proinflammatory molecules were still present in these supernatants. Cholera remains a devastating bacterial cause of human morbidity and mortality in some areas of the world (1). The disease is produced by Vibrio cholerae, a Gram-negative curved rod that colonizes the human intestine where it secretes the potent cholera toxin (CT), 1 which ultimately stimulates cellular adenylate cyclase to cause massive intestinal fluid loss leading to profuse watery diarrhea. CT is the major V. cholerae virulence factor, and it is encoded by the ctxA and ctxB genes carried on the transmissible prophage CTX⌽ (2). V. cholerae produces an array of virulence factors, which are coordinately regulated by the transcriptional activator ToxR (3). In turn, ToxR activates ToxT, a second transcriptional regulator that activates the expression of CT and the toxincoregulated pilus (TCP) (4, 5). TCP is considered the most important intestinal colonization factor of V. cholerae (6).In addition to CT, the accessory cholera toxin (Ace) (7) and the zonula occludens toxin (Zot) (7, 8) were reported as potential cytotoxic factors, but these proteins were later demonstrated to be components of a filamentous bacteriophage (2). Several in vitro studies have shown that V. cholerae secretes other cytotoxic factors such as the hemagglutinin/ protease (HAP), hemolysin (Hly), and repeats-in-toxin (RTX) (9 -11). These cytotoxic factors may cause tissue damage by different mechanisms that could contribute to proinflammatory responses. However, only RTX mutants have been demonstrated in a murine pulmonary cholera model to show less severe pathology and decreased serum levels of proinflammatory IL-6 and murine macrophage inflammatory protein-2, suggesting that RTX participates in the severity of acute inflammatory responses (12).Research on cholera vaccines has focused largely on oral formulations that stimulate the mucosal immune system thereby mimicking natural infection (13). Through the years, different formulations of cholera vaccines have been proposed that include formalin or heat-killed bacteria alone or in combination with CT B-subunit. As new putative virulence factors ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.