ORCID Profile
0000-0002-7009-1548
Current Organisation
University of Southampton
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: BMJ
Date: 04-2011
Publisher: Public Library of Science (PLoS)
Date: 04-09-2014
Publisher: Elsevier BV
Date: 08-2011
Publisher: American Society for Microbiology
Date: 04-2016
DOI: 10.1128/AAC.02432-15
Abstract: Streptococcus pneumoniae is one of the key pathogens responsible for otitis media (OM), the most common infection in children and the largest cause of childhood antibiotic prescription. Novel therapeutic strategies that reduce the overall antibiotic consumption due to OM are required because, although widespread pneumococcal conjugate immunization has controlled invasive pneumococcal disease, overall OM incidence has not decreased. Biofilm formation represents an important phenotype contributing to the antibiotic tolerance and persistence of S. pneumoniae in chronic or recurrent OM. We investigated the treatment of pneumococcal biofilms with nitric oxide (NO), an endogenous signaling molecule and therapeutic agent that has been demonstrated to trigger biofilm dispersal in other bacterial species. We hypothesized that addition of low concentrations of NO to pneumococcal biofilms would improve antibiotic efficacy and that higher concentrations exert direct antibacterial effects. Unlike in many other bacterial species, low concentrations of NO did not result in S. pneumoniae biofilm dispersal. Instead, treatment of both in vitro biofilms and ex vivo adenoid tissue s les (a reservoir for S. pneumoniae biofilms) with low concentrations of NO enhanced pneumococcal killing when combined with amoxicillin-clavulanic acid, an antibiotic commonly used to treat chronic OM. Quantitative proteomic analysis using iTRAQ (isobaric tag for relative and absolute quantitation) identified 13 proteins that were differentially expressed following low-concentration NO treatment, 85% of which function in metabolism or translation. Treatment with low-concentration NO, therefore, appears to modulate pneumococcal metabolism and may represent a novel therapeutic approach to reduce antibiotic tolerance in pneumococcal biofilms.
Publisher: Microbiology Society
Date: 10-2019
DOI: 10.1099/JMM.0.001046
Publisher: Oxford University Press (OUP)
Date: 15-04-2016
DOI: 10.1093/GBE/EVW072
Publisher: Microbiology Society
Date: 10-2010
Abstract: Data from 4727 invasive isolates of Streptococcus pneumoniae submitted to the Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory between 1999 and 2007 were analysed to establish susceptibility profiles to penicillin, erythromycin and cefotaxime. Pneumococcal resistance to penicillin over the study period remained low, with only 0.2 % ( n =7/4727) of isolates falling into this category (MIC ≥2 mg l −1 ). These isolates have been sporadic, and have mainly represented serogroup 14 (ST9) and 9 (ST156). In comparison, the ‘intermediate sensitivity’ group (MIC 0.12–1 mg l −1 ) ranged between 2 and 6 % per year, the majority from serogroup 9 (ST156). Over the study period, we found that 12 % ( n =585/4727) of isolates were erythromycin-resistant (MIC .5 mg l −1 ), with the majority ( n =467 80 %) of these isolates identified as serogroup 14 (ST9). Cephalosporin resistance (cefotaxime MIC mg l −1 ) was found in only 0.06 % ( n =2/3135) of isolates. Internationally recognized clones (Pneumococcal Molecular Epidemiology Network) accounted for 35 % ( n =28/81) of the penicillin non-susceptible isolates and 75 % ( n =248/330) of the macrolide-resistant isolates, with ST9 and ST306 predominating. Between 1999 and 2007 we found that 11.6 % ( n =18/155) of the penicillin non-susceptible isolates and 4.8 % ( n =28/585) of the macrolide-resistant isolates were from serogroups not covered by the 7-valent conjugate pneumococcal vaccine in use in the UK since 2006. Susceptibility to first-line antimicrobial agents for invasive pneumococcal disease in Scotland remained high over the period 1999–2007.
Publisher: Oxford University Press (OUP)
Date: 24-03-2016
DOI: 10.1093/GBE/EVW066
Publisher: Elsevier BV
Date: 06-2015
Publisher: Oxford University Press (OUP)
Date: 10-2011
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1016/J.JGAR.2022.08.019
Abstract: To analyse the genome sequences of four archival Acinetobacter nosocomialis clinical isolates (designated AC13, AC15, AC21 and AC25) obtained from Terengganu, Malaysia in 2011 to determine their genetic relatedness and basis of antimicrobial resistance. Antimicrobial susceptibility profiles of the A. nosocomialis isolates were determined by disk diffusion. Genome sequencing was performed using the Illumina NextSeq platform. The four A. nosocomialis isolates were cefotaxime resistant whereas three isolates (namely, AC13, AC15 and AC25) were tetracycline resistant. The carriage of the bla Genome sequencing of A. nosocomialis isolates led to the discovery of two novel plasmids, one of which encodes the tetA(39) tetracycline-resistant gene in a mobile pdif module. The high degree of genetic relatedness among the three tetracycline-resistant A. nosocomialis isolates is indicative of nosocomial transmission.
Publisher: Springer Science and Business Media LLC
Date: 25-03-2017
Publisher: Oxford University Press (OUP)
Date: 15-09-2007
DOI: 10.1086/520091
Abstract: Pneumolysin is an important virulence factor of the human pathogen Streptococcus pneumoniae. Sequence analysis of the ply gene from 121 clinical isolates of S. pneumoniae uncovered a number of alleles. Twenty-two strains were chosen for further analysis, and 14 protein alleles were discovered. Five of these had been reported previously, and the remaining 9 were novel. Cell lysates were used to determine the specific hemolytic activities of the pneumolysin proteins. Six strains showed no hemolytic activity, and the remaining 16 were hemolytic, to varying degrees. We report that the nonhemolytic allele reported previously in serotype 1, sequence type (ST) 306 isolates is also present in a number of pneumococcal isolates of serotype 8 that belong to the ST53 lineage. Serotype 1 and 8 pneumococci are known to be associated with outbreaks of invasive disease. The nonhemolytic pneumolysin allele is therefore associated with the dominant clones of outbreak-associated serotypes of S. pneumoniae.
Publisher: Microbiology Society
Date: 06-2011
Publisher: Oxford University Press (OUP)
Date: 03-2008
DOI: 10.1086/527401
Abstract: Background. In 1999, meningococcal serogroup C conjugate (MCC) vaccines were introduced in the United Kingdom for those under 19 years of age. The impact of this intervention on asymptomatic carriage of meningococci was investigated to establish whether serogroup replacement or protection by herd immunity occurred. Methods. Multicenter surveys of carriage were conducted during vaccine introduction and on 2 successive years, resulting in a total of 48,309 s les, from which 8599 meningococci were isolated and characterized by genotyping and phenotyping. Results. A reduction in serogroup C carriage (rate ratio, 0.19) was observed that lasted at least 2 years with no evidence of serogroup replacement. Vaccine efficacy against carriage was 75%, and vaccination had a disproportionate impact on the carriage of sequence type (ST)-11 complex serogroup C meningococci that (rate ratio, 0.06) these meningococci also exhibited high rates of capsule expression. Conclusions. The impact of vaccination with MCC vaccine on the prevalence of carriage of group C meningococci was consistent with herd immunity. The high impact on the carriage of ST-11 complex serogroup C could be attributed to high levels of capsule expression. High vaccine efficacy against disease in young children, who were not protected long-term by the schedule initially used, is attributed to the high vaccine efficacy against carriage in older age groups.
Publisher: Elsevier BV
Date: 09-2017
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.NIOX.2017.02.006
Abstract: Bacterial biofilms show high tolerance towards antibiotics and are a significant problem in clinical settings where they are a primary cause of chronic infections. Novel therapeutic strategies are needed to improve anti-biofilm efficacy and support reduction in antibiotic use. Treatment with exogenous nitric oxide (NO) has been shown to modulate bacterial signaling and metabolic processes that render biofilms more susceptible to antibiotics. We previously reported on cephalosporin-3'-diazeniumdiolates (C3Ds) as NO-donor prodrugs designed to selectively deliver NO to bacterial infection sites following reaction with β-lactamases. With structures based on cephalosporins, C3Ds could, in principal, also be triggered to release NO following β-lactam cleavage mediated by transpeptidases enicillin-binding proteins (PBPs), the antibacterial target of cephalosporin antibiotics. Transpeptidase-reactive C3Ds could potentially show both NO-mediated anti-biofilm properties and intrinsic (β-lactam-mediated) antibacterial effects. This dual-activity concept was explored using Streptococcus pneumoniae, a species that lacks β-lactamases but relies on transpeptidases for cell-wall synthesis. Treatment with PYRRO-C3D (a representative C3D containing the diazeniumdiolate NO donor PYRRO-NO) was found to significantly reduce viability of planktonic and biofilm pneumococci, demonstrating that C3Ds can elicit direct, cephalosporin-like antibacterial activity in the absence of β-lactamases. While NO release from PYRRO-C3D in the presence of pneumococci was confirmed, the anti-pneumococcal action of the compound was shown to arise exclusively from the β-lactam component and not through NO-mediated effects. The compound showed similar potency to amoxicillin against S. pneumoniae biofilms and greater efficacy than azithromycin, highlighting the potential of C3Ds as new agents for treating pneumococcal infections.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Stuart Clarke.