Synthesis of Rare 6-Deoxy-d-/l-Heptopyranosyl Fluorides: Assembly of a Hexasaccharide Corresponding to Campylobacter jejuni Strain CG8486 Capsular Polysaccharide

2021 ◽  
Vol 143 (29) ◽  
pp. 11171-11179
Author(s):  
Tiantian Li ◽  
Jianjun Wang ◽  
Xinhao Zhu ◽  
Xin Zhou ◽  
Shaozi Sun ◽  
...  
2017 ◽  
Vol 85 (6) ◽  
Author(s):  
Orhan Sahin ◽  
Samantha A. Terhorst ◽  
Eric R. Burrough ◽  
Zhangqi Shen ◽  
Zuowei Wu ◽  
...  

ABSTRACT Campylobacter jejuni is a zoonotic pathogen, and a hypervirulent clone, named clone SA, has recently emerged as the predominant cause of ovine abortion in the United States. To induce abortion, orally ingested Campylobacter must translocate across the intestinal epithelium, spread systemically in the circulation, and reach the fetoplacental tissue. Bacterial factors involved in these steps are not well understood. C. jejuni is known to produce capsular polysaccharide (CPS), but the specific role that CPS plays in systemic infection and particularly abortion in animals remains to be determined. In this study, we evaluated the role of CPS in bacteremia using a mouse model and in abortion using a pregnant guinea pig model following oral challenge. Compared with C. jejuni NCTC 11168 and 81-176, a clone SA isolate (IA3902) resulted in significantly higher bacterial counts and a significantly longer duration of bacteremia in mice. The loss of capsule production via gene-specific mutagenesis in IA3902 led to the complete abolishment of bacteremia in mice and abortion in pregnant guinea pigs, while complementation of capsule expression almost fully restored these phenotypes. The capsule mutant strain was also impaired for survival in guinea pig sera and sheep blood. Sequence-based analyses revealed that clone SA possesses a unique CPS locus with a mosaic structure, which has been stably maintained in all clone SA isolates derived from various hosts and times. These findings establish CPS as a key virulence factor for the induction of systemic infection and abortion in pregnant animals and provide a viable candidate for the development of vaccines against hypervirulent C. jejuni.


2008 ◽  
Vol 190 (6) ◽  
pp. 1879-1890 ◽  
Author(s):  
Baoqing Guo ◽  
Ying Wang ◽  
Feng Shi ◽  
Yi-Wen Barton ◽  
Paul Plummer ◽  
...  

ABSTRACT CmeR functions as a transcriptional repressor modulating the expression of the multidrug efflux pump CmeABC in Campylobacter jejuni. To determine if CmeR also regulates other genes in C. jejuni, we compared the transcriptome of the cmeR mutant with that of the wild-type strain using a DNA microarray. This comparison identified 28 genes that showed a ≥2-fold change in expression in the cmeR mutant. Independent real-time quantitative reverse transcription-PCR experiments confirmed 27 of the 28 differentially expressed genes. The CmeR-regulated genes encode membrane transporters, proteins involved in C4-dicarboxylate transport and utilization, enzymes for biosynthesis of capsular polysaccharide, and hypothetical proteins with unknown functions. Among the genes whose expression was upregulated in the cmeR mutant, Cj0561c (encoding a putative periplasmic protein) showed the greatest increase in expression. Subsequent experiments demonstrated that this gene is strongly repressed by CmeR. The presence of the known CmeR-binding site, an inverted repeat of TGTAAT, in the promoter region of Cj0561c suggests that CmeR directly inhibits the transcription of Cj0561c. Similar to expression of cmeABC, transcription of Cj0561c is strongly induced by bile compounds, which are normally present in the intestinal tracts of animals. Inactivation of Cj0561c did not affect the susceptibility of C. jejuni to antimicrobial compounds in vitro but reduced the fitness of C. jejuni in chickens. Loss-of-function mutation of cmeR severely reduced the ability of C. jejuni to colonize chickens. Together, these findings indicate that CmeR governs the expression of multiple genes with diverse functions and is required for Campylobacter adaptation in the chicken host.


2007 ◽  
Vol 73 (24) ◽  
pp. 7959-7966 ◽  
Author(s):  
Christopher Pope ◽  
Janet Wilson ◽  
Eduardo N. Taboada ◽  
Joanne MacKinnon ◽  
Cristiano A. Felipe Alves ◽  
...  

ABSTRACT One hundred forty-one Campylobacter jejuni isolates from humans with diarrhea and 100 isolates from retailed poultry meat were differentiated by flaA typing. The bacteria were isolated in a specific geographical area (Dunedin) in New Zealand over a common time period. Twenty nine flaA types were detected, one of which (flaA restriction fragment length polymorphism type 15 [flaA-15]) predominated among isolates from humans (∼30% of isolates). This strain was of low prevalence (5% of isolates) among poultry isolates. flaA-15 strains were five to six times more invasive of HEp2 cells in an in vitro assay than a flaA type (flaA-3) that was commonly encountered on poultry meat (23% of isolates) but was seldom associated with human illness (5%). Competitive-exclusion experiments with chickens, utilizing real-time quantitative PCR to measure the population sizes of specific strains representing flaA-15 (T1016) and flaA-3 (Pstau) in digesta, were carried out. These experiments showed that T1016 always outcompeted Pstau in the chicken intestine. Genomic comparisons of T1016 and Pstau were made using DNA microarrays representing the genome of C. jejuni NCTC 11168. These comparisons revealed differences between the strains in the gene content of the Cj1417c-to-Cj1442c region of the genome, which is associated with the formation of capsular polysaccharide. The strains differed in Penner type (T1016, O42; Pstau, O53). It was concluded that poultry meat was at least one source of human infection with C. jejuni, that some Campylobacter strains detected in poultry meat are of higher virulence for humans than others, and that bacterial attributes affecting strain virulence and commensal colonization ability may be linked.


2021 ◽  
Vol 12 ◽  
Author(s):  
Athina Zampara ◽  
Martine C. Holst Sørensen ◽  
Yilmaz Emre Gencay ◽  
Dennis Grimon ◽  
Sebastian Hougaard Kristiansen ◽  
...  

Campylobacter contaminated poultry remains the major cause of foodborne gastroenteritis worldwide, calling for novel antibacterials. We previously developed the concept of Innolysin composed of an endolysin fused to a phage receptor binding protein (RBP) and provided the proof-of-concept that Innolysins exert bactericidal activity against Escherichia coli. Here, we have expanded the Innolysin concept to target Campylobacter jejuni. As no C. jejuni phage RBP had been identified so far, we first showed that the H-fiber originating from a CJIE1-like prophage of C. jejuni CAMSA2147 functions as a novel RBP. By fusing this H-fiber to phage T5 endolysin, we constructed Innolysins targeting C. jejuni (Innolysins Cj). Innolysin Cj1 exerts antibacterial activity against diverse C. jejuni strains after in vitro exposure for 45 min at 20°C, reaching up to 1.30 ± 0.21 log reduction in CAMSA2147 cell counts. Screening of a library of Innolysins Cj composed of distinct endolysins for growth inhibition, allowed us to select Innolysin Cj5 as an additional promising antibacterial candidate. Application of either Innolysin Cj1 or Innolysin Cj5 on chicken skin refrigerated to 5°C and contaminated with C. jejuni CAMSA2147 led to 1.63 ± 0.46 and 1.18 ± 0.10 log reduction of cells, respectively, confirming that Innolysins Cj can kill C. jejuni in situ. The receptor of Innolysins Cj remains to be identified, however, the RBP component (H-fiber) recognizes a novel receptor compared to lytic phages binding to capsular polysaccharide or flagella. Identification of other unexplored Campylobacter phage RBPs may further increase the repertoire of new Innolysins Cj targeting distinct receptors and working as antibacterials against Campylobacter.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoqi Zang ◽  
Hongyue Lv ◽  
Haiyan Tang ◽  
Xinan Jiao ◽  
Jinlin Huang

Campylobacter jejuni (C. jejuni) is the leading causative agent of gastroenteritis and Guillain–Barré syndrome (GBS). Capsular polysaccharide (CPS) and lipooligosaccharide (LOS) contribute to the susceptibility of campylobacteriosis, which have been concern the major evaluation indicators of C. jejuni isolates from clinical patients. As a foodborne disease, food animal plays a primary role in the infection of campylobacteriosis. To assess the pathogenic characterizations of C. jejuni isolates from various ecological origins, 1609 isolates sampled from 2005 to 2019 in China were analyzed using capsular genotyping. Strains from cattle and poultry were further characterized by LOS classification and multilocus sequence typing (MLST), compared with the isolates from human patients worldwide with enteritis and GBS. Results showed that the disease associated capsular genotypes and LOS classes over-represented in human isolates were also dominant in animal isolates, especially cattle isolates. Based on the same disease associated capsular genotype, more LOS class types were represented by food animal isolates than human disease isolates. Importantly, high-risk lineages CC-22, CC-464, and CC-21 were found dominated in human isolates with GBS worldwide, which were also represented in the food animal isolates with disease associated capsular types, suggesting a possibility of clonal spread of isolates across different regions and hosts. This is the first study providing genetic evidence for food animal isolates of particular capsular genotypes harbor similar pathogenic characteristics to human clinical isolates. Collective efforts for campylobacteriosis hazard control need to be focused on the zoonotic pathogenicity of animal isolates, along the food chain “from farm to table.”


FEBS Journal ◽  
2005 ◽  
Vol 272 (17) ◽  
pp. 4407-4422 ◽  
Author(s):  
David J. McNally ◽  
Harold C. Jarrell ◽  
Jianjun Li ◽  
Nam H. Khieu ◽  
Evgeny Vinogradov ◽  
...  

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