Publications

@article{Osborne2025-gb,

title = {Alpha-linolenic acid-modified liposomes associate with and  modulate antibiotic activity against Helicobacter pylori},

author = {Nicola C Osborne and Rosa Catania and Snow Stolnik and Karen Robinson},

doi = {10.1099/mic.0.001562},

year  = {2025},

date = {2025-05-01},

urldate = {2025-05-01},

journal = {Microbiology},

volume = {171},

number = {5},

abstract = {Fatty acids have antimicrobial activity against a wide range of 

 bacteria. We therefore aimed to incorporate omega-3 unsaturated 

 alpha-linolenic acid (αLA) into the membrane of 

 antibiotic-loaded liposomes to create a system with dual 

 antibacterial activity against Helicobacter pylori. Liposomes 

 containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, 

 cholesterol, sphingomyelin and the far-red fluorescent DiD label, 

 with varying content of αLA (mol% to total lipid), were 

 fabricated using the thin film evaporation method and hydrated 

 with PBS or amoxicillin solution. The liposomes were 

 characterized for αLA and amoxicillin content, particle 

 size, membrane fluidity and permeability, prior to their addition 

 to cultures of H. pylori strains and clinical isolates. 

 αLA-modified liposomes enhanced the antibacterial action 

 of amoxicillin against H. pylori, as determined using a viable 

 count method. The liposomal formulation achieved a 3-log 

 reduction in bacterial density, compared to a 1.5- to 2-log 

 reduction by amoxicillin in solution. The application of imaging 

 cytometry revealed a significantly increased association of 

 αLA-modified liposomes with H. pylori cells, compared to 

 non-αLA control liposomes. In conclusion, this study 

 demonstrated, for the first time, that the incorporation of 

 αLA increased the attraction of the liposomes to H. pylori 

 and increased antibiotic potency. This suggests that αLA 

 incorporation into liposomes may not only act as an 

 antimicrobial, but also as a potential in vivo targeting 

 strategy.},

keywords = {antibiotics, fatty acids, Helicobacter pylori, linolenic acid, liposomes},

pubstate = {published},

tppubtype = {article}

}

@article{Garvey2023-ao,

title = {High incidence of antibiotic resistance amongst isolates of 

 Helicobacter pylori collected in Nottingham, UK, between 2001 

 and 2018},

author = {Elizabeth Garvey and Joanne Rhead and Suffi Suffian and Daniel Whiley and Farah Mahmood and Naveen Bakshi and Darren Letley and Jonathan White and John Atherton and Jody Anne Winter and Karen Robinson},

year  = {2023},

date = {2023-11-01},

journal = {J. Med. Microbiol.},

volume = {72},

number = {11},

publisher = {Microbiology Society},

abstract = {Introduction. Helicobacter pylori is the leading cause of peptic 

 ulcers and gastric cancer. The most common treatment regimens 

 use combinations of two or three antibiotics and a proton pump 

 inhibitor (PPI) to suppress stomach acid. The World Health 

 Organization designated clarithromycin-resistant H. pylori as a 

 high priority pathogen for drug development, due to increasing 

 antibiotic resistance globally.Hypothesis/Gap Statement. There 

 is no routine surveillance of H. pylori primary antimicrobial 

 sensitivities in the UK, and published data are lacking.Aim. 

 This study aimed to characterize antimicrobial sensitivities of 

 isolates collected in Nottingham, UK, between 2001 and 

 2018.Methodology. Gastric biopsy samples were collected, with 

 informed written consent and ethics approval, from 162 patients 

 attending the Queen's Medical Centre in Nottingham for an upper 

 GI tract endoscopy. Antibiotic sensitivity was assessed using 

 E-Tests and a more cost-effective disc diffusion test.Results. 

 The clarithromycin, amoxicillin and levofloxacin disc diffusion 

 tests provided identical results to E-Tests on a subset of 30 

 isolates. Disparities were observed in the metronidazole test 

 results, however. In total, 241 isolates from 162 patients were 

 tested using at least one method. Of all isolates, 28 % were 

 resistant to clarithromycin, 62 % to metronidazole and 3 % to 

 amoxicillin, which are used in first-line therapies. For those 

 antibiotics used in second- and third-line therapies, 4 % were 

 resistant to levofloxacin and none of the isolates were 

 resistant to tetracycline. Resistance to more than one 

 antibiotic was found in 27 % of isolates. The frequency of 

 patients with a clarithromycin-resistant strain increased 

 dramatically over time: from 16 % between 2001 and 2005 to 40 % between 2011 and 2018 (P=0.011). For the same time periods, 

 there was also an increase in those with a metronidazole-resistant strain (from 58 to 78 %; P=0.05). The 

 frequencies of clarithromycin and metronidazole resistance were 

 higher in isolates from patients who had previously received 

 eradication therapy, compared to those who had not (40 % versus 

 77 %, and 80 % versus 92 %, respectively). Of 79 pairs of 

 isolates from the antrum and corpus regions of the same 

 patient's stomach, only six had differences in their 

 antimicrobial susceptibility profiles.Conclusion. Although there 

 was high and increasing resistance to clarithromycin and 

 metronidazole, there was no resistance to tetracycline and the 

 frequencies of amoxicillin and levofloxacin resistance were very 

 low.},

keywords = {amoxicillin, antimicrobial resistance, clarithromycin, Helicobacter pylori, levofloxacin, metronidazole, susceptibility   testing},

pubstate = {published},

tppubtype = {article}

}

@article{Kaneko2022-jg,

title = {The active form of Helicobacter pylori vacuolating cytotoxin 

 induces decay-accelerating factor CD55 in association with 

 intestinal metaplasia in the human gastric mucosa},

author = {Kazuyo Kaneko and Abed M Zaitoun and Darren P Letley and Joanne L Rhead and Javier Torres and Ian Spendlove and John C Atherton and Karen Robinson},

year  = {2022},

date = {2022-10-01},

journal = {J. Pathol.},

volume = {258},

number = {2},

pages = {199\textendash209},

publisher = {Wiley},

abstract = {High-level expression of decay-accelerating factor, CD55, has 

 previously been found in human gastric cancer (GC) and 

 intestinal metaplasia (IM) tissues. Therapeutic effects of CD55 

 inhibition in cancer have been reported. However, the role of 

 Helicobacter pylori infection and virulence factors in the 

 induction of CD55 and its association with histological changes 

 of the human gastric mucosa remain incompletely understood. We 

 hypothesised that CD55 would be increased during infection with 

 more virulent strains of H. pylori, and with more marked gastric 

 mucosal pathology. RT-qPCR and immunohistochemical analyses of 

 gastric biopsy samples from 42 H. pylori-infected and 42 

 uninfected patients revealed that CD55 mRNA and protein were 

 significantly higher in the gastric antrum of H. pylori-infected 

 patients, and this was associated with the presence of IM, but 

 not atrophy, or inflammation. Increased gastric CD55 and IM were 

 both linked with colonisation by vacA i1-type strains 

 independently of cagA status, and in vitro studies using 

 isogenic mutants of vacA confirmed the ability of VacA to induce 

 CD55 and sCD55 in gastric epithelial cell lines. siRNA 

 experiments to investigate the function of H. pylori-induced 

 CD55 showed that CD55 knockdown in gastric epithelial cells 

 partially reduced IL-8 secretion in response to H. pylori, but 

 this was not due to modulation of bacterial adhesion or 

 cytotoxicity. Finally, plasma samples taken from the same 

 patients were analysed for the soluble form of CD55 (sCD55) by 

 ELISA. sCD55 levels were not influenced by IM and did not 

 correlate with gastric CD55 mRNA levels. These results suggest a 

 new link between active vacA i1-type H. pylori, IM, and CD55, 

 and identify CD55 as a molecule of potential interest in the 

 management of IM as well as GC treatment. © 2022 The 

 Authors. The Journal of Pathology published by John Wiley \& 

 Sons Ltd on behalf of The Pathological Society of Great Britain 

 and Ireland.},

keywords = {CD55, decay-accelerating factor, gastric   cancer, Helicobacter pylori, intestinal metaplasia, vacuolating cytotoxin, virulence   factor},

pubstate = {published},

tppubtype = {article}

}

@article{Robinson2021-la,

title = {The spectrum of Helicobacter-mediated diseases},

author = {Karen Robinson and John C Atherton},

year  = {2021},

date = {2021-01-01},

journal = {Annu. Rev. Pathol.},

volume = {16},

number = {1},

pages = {123\textendash144},

publisher = {Annual Reviews},

abstract = {Helicobacter pylori is the leading cause of peptic ulcer 

 disease. The infection has been implicated in more than 75% of 

 duodenal ulcer cases and 17% of gastric ulcer cases. H. pylori 

 has been classified as a human carcinogen, since it is the main 

 cause of distal gastric adenocarcinoma and B cell 

 mucosa-associated lymphoid tissue lymphoma. Evidence also links 

 H. pylori with extragastric conditions including iron deficiency 

 anemia, idiopathic thrombocytopenic purpura, and vitamin B12 

 deficiency. Studies indicate that H. pylori may be protective 

 against other conditions of the gastrointestinal tract (e.g., 

 reflux esophagitis and related pathologies) and elsewhere in the 

 body (e.g., asthma). The infection is asymptomatic in the vast 

 majority of cases; more serious outcomes occur in only 10-15% 

 of infected individuals. Despite extensive research over the 

 past 3 decades, there is no effective vaccine, and the 

 circumstances leading to disease development remain unclear. In 

 addition, there is now a growing prevalence of antimicrobial 

 resistance in H. pylori. This review discusses these important 

 issues.},

keywords = {antimicrobial resistance, duodenal ulcer, gastric adenocarcinoma, gastric ulcer, gastritis, Helicobacter pylori, MALT lymphoma, reflux esophagitis},

pubstate = {published},

tppubtype = {article}

}

@article{Robinson2020-vc,

title = {Review - Helicobacter, inflammation, immunology and vaccines},

author = {Karen Robinson and Philippe Lehours},

year  = {2020},

date = {2020-09-01},

journal = {Helicobacter},

volume = {25 Suppl 1},

number = {S1},

pages = {e12737},

publisher = {Wiley},

abstract = {Understanding the mechanisms involved in induction and 

 regulation of the immune and inflammatory response to 

 Helicobacter pylori is extremely important in determining 

 disease outcomes. H pylori expresses a plethora of factors that 

 influence the host response. Vaccines against H pylori are 

 desperately needed for the prevention of gastric carcinogenesis, 

 especially with the increasing trends in antimicrobial 

 resistance. This review summarizes some important findings, 

 published between 1 April 2019 and 31 March 2020, in the areas 

 of H pylori-mediated inflammation, immunity and vaccines.},

keywords = {adaptive immunity, cytokines, Helicobacter pylori, inflammation, innate immunity, vaccines},

pubstate = {published},

tppubtype = {article}

}