Johanna M. Jefferies

University of Southampton

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Stuart C. Clarke

University of Southampton

Saul N. Faust

University Hospital Southampton NHS Foundation Trust

Timothy J. Mitchell

Forth Valley Royal Hospital

Rebecca A. Gladstone

University of Oslo

David Cleary

University of Birmingham

Jeremy S. Webb

University of Southampton

Giles Edwards

Stobhill Hospital

Andrew Smith

University of Glasgow

Anna S. Tocheva

Icahn School of Medicine at Mount Sinai

Jim McMenamin

Public Health Scotland

Cooperative Institutions

University of Southampton

University Hospital Southampton NHS Foundation Trust

Southampton General Hospital

NIHR Southampton Biomedical Research Centre

NIHR Southampton Respiratory Biomedical Research Unit

National Institute for Health Research

GlaxoSmithKline (Belgium)

University of Glasgow

Public Health England

University of Oxford

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Pronounced Metabolic Changes in Adaptation to Biofilm Growth by Streptococcus pneumoniae

PLoS ONE (2014)

R N Allan Paul Skipp Johanna M. Jefferies Stuart C. Clarke Saul N. Faust

Streptococcus pneumoniae accounts for a significant global burden of morbidity and mortality and biofilm development is increasingly recognised as important for colonization and infection. Analysis of protein expression patterns during biofilm development may therefore provide valuable insights to the understanding of pneumococcal persistence strategies and to improve vaccines. iTRAQ (isobaric tagging for relative and absolute quantification), a high-throughput gel-free proteomic approach which allows high resolution quantitative comparisons of protein profiles between multiple phenotypes, was used to interrogate planktonic and biofilm growth in a clinical serotype 14 strain. Comparative analyses of protein expression between log-phase planktonic and 1-day and 7-day biofilm cultures representing nascent and late phase biofilm growth were carried out. Overall, 244 proteins were identified, of which >80% were differentially expressed during biofilm development. Quantitatively and qualitatively, metabolic regulation appeared to play a central role in the adaptation from the planktonic to biofilm phenotype. Pneumococci adapted to biofilm growth by decreasing enzymes involved in the glycolytic pathway, as well as proteins involved in translation, transcription, and virulence. In contrast, proteins with a role in pyruvate, carbohydrate, and arginine metabolism were significantly increased during biofilm development. Downregulation of glycolytic and translational proteins suggests that pneumococcus adopts a covert phenotype whilst adapting to an adherent lifestyle, while utilization of alternative metabolic pathways highlights the resourcefulness of pneumococcus to facilitate survival in diverse environmental conditions. These metabolic proteins, conserved across both the planktonic and biofilm phenotypes, may also represent target candidates for future vaccine development and treatment strategies. Data are available via ProteomeXchange with identifier PXD001182.

Proteome

10.1371/journal.pone.0107015

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Citations (48)

Novel Clones of Streptococcus pneumoniae Causing Invasive Disease in Malaysia

PLoS ONE (2014)

Johanna M. Jefferies Mohd Yasim Mohd Yusof Shamala Devi Sekaran Stuart C. Clarke

Although Streptococcus pneumoniae is a leading cause of childhood disease in South East Asia, little has previously been reported regarding the epidemiology of invasive pneumococcal disease in Malaysia and very few studies have explored pneumococcal epidemiology using multilocus sequence typing (MLST). Here we describe serotype, multilocus sequence type (ST), and penicillin susceptibility of thirty pneumococcal invasive disease isolates received by the University of Malaya Medical Centre between February 2000 and January 2007 and relate this to the serotypes included in current pneumococcal conjugate vaccines. A high level of diversity was observed; fourteen serotypes and 26 sequence types (ST), (11 of which were not previously described) were detected from 30 isolates. Penicillin non-susceptible pneumococci accounted for 33% of isolates. The extent of molecular heterogeneity within carried and disease-causing Malaysian pneumococci remains unknown. Larger surveillance and epidemiological studies are now required in this region to provide robust evidence on which to base future vaccine policy.

Multilocus sequence typing

Molecular Epidemiology

Pneumococcal infections

Pneumococcal Conjugate Vaccine

10.1371/journal.pone.0097912

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Citations (14)

Current methods for capsular typing of Streptococcus pneumoniae

Journal of Microbiological Methods (2015)

Elita Jauneikaite Anna S. Tocheva Johanna M. Jefferies Rebecca A. Gladstone Saul N. Faust

Pneumococcal Conjugate Vaccine

Pneumococcal infections

Gold standard (test)

Pneumococcal vaccine

10.1016/j.mimet.2015.03.006

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Citations (80)

Lifestyle risk factors for invasive pneumococcal disease: a systematic review

BMJ Open (2014)

Helen C Cruickshank Johanna M. Jefferies Stuart C. Clarke

Objective To systematically review the literature for evidence of smoking and alcohol intake as independent risk factors for invasive pneumococcal disease (IPD). Design Systematic review. Methods MEDLINE (1946—May 2012) and EMBASE (1947—May 2012) were searched for studies investigating alcohol or smoking as risk factors for acquiring IPD and which reported results as relative risk. Studies conducted exclusively in clinical risk groups, those assessing risk factors for outcomes other than acquisition of IPD and studies describing risk factors without quantifying a relative risk were excluded. Results Seven observational studies were identified and reviewed; owing to the heterogeneity of study design, meta-analysis was not attempted. Five of six studies investigating smoking reported an increased risk of IPD in the range 2.2–4.1. Four of the six studies investigating alcohol intake reported a significant increased risk for IPD ranging from 2.9 to 11.4, while one reported a significant protective effect. Conclusions Overall, these observational data suggest that smoking and alcohol misuse may increase the risk of IPD in adults, but the magnitude of this risk remains unclear and should be explored with further research. The findings of this review will contribute to the debate on whether pneumococcal vaccine should be offered to smokers and people who misuse alcohol in addition to other clinically defined risk groups.

10.1136/bmjopen-2014-005224

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Changes in serotype prevalence of Streptococcus pneumoniae in Southampton, UK between 2006 and 2018

Scientific Reports (2022)

David Cleary Jessica Jones Rebecca A. Gladstone Karen L. Osman Vanessa T. Devine

Streptococcus pneumoniae continues to cause significant disease burden. Whilst pneumococcal conjugate vaccines (PCV) have substantially reduced this burden, serotype replacement partially negates this success due to increased disease associated with non-vaccine serotypes (NVTs). Continued surveillance is therefore essential to provide crucial epidemiological data. Annual cross-sectional surveillance of paediatric pneumococcal carriage was started in Southampton, UK following PCV7 roll-out in 2006. Nasopharyngeal swabs were collected from children < 5 years old each winter (October to March) from 2006/07 and for each consecutive year until 2017/18. Pneumococcal serotype was inferred from whole genome sequencing data. A total of 1429 (32.5%) pneumococci were isolated from 4093 children. Carriage ranged from 27.8% (95%CI 23.7-32.7) in 2008/09 to 37.9% (95%CI 32.8-43.2) in 2014/15. Analyses showed that carriage increased in children aged 24-35 months (p < 0.001) and 47-60 months (p < 0.05). Carriage of PCV serotypes decreased markedly following PCV7 and/or PCV13 introduction, apart from serotype 3 where the relative frequency was slightly lower post-PCV13 (pre-PCV13 n = 7, 1.67%; post-PCV13 n = 13, 1.27%). Prevalence of NVTs implicated in increased disease was low with 24F (n = 19, 1.4%) being the most common followed by 9N (n = 11, 0.8%), 8 (n = 7, 0.5%) and 12F (n = 3, 0.2%).

Carriage

Pneumococcal Conjugate Vaccine

Pneumococcal infections

10.1038/s41598-022-17600-6

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Citations (29)

Pseudomonas aeruginosa outbreaks in the neonatal intensive care unit – a systematic review of risk factors and environmental sources

Journal of Medical Microbiology (2012)

Johanna M. Jefferies Tracey Cooper T. Yam Stuart C. Clarke

Pseudomonas aeruginosa is a Gram-negative bacterium commonly occurring in soil and water. It is an opportunistic pathogen and an important cause of healthcare-associated infections, particularly among infants in neonatal intensive care units (NICUs). Several reports regarding outbreaks of P. aeruginosa in NICUs have been published. MEDLINE and EMBASE databases were searched using the MeSH terms [Pseudomonas aeruginosa], [Outbreak OR Infection OR bacteraemia, OR sepsis OR disease] and [Neonat* OR baby OR babies OR newborn*]. Fifteen studies describing a total of 414 infants colonized or infected with P. aeruginosa were reviewed. The mean percentage of infections occurring in the populations that had been colonized by the organism (calculated as n(infected)/n(infected)+n(colonized)) was 22%. Environmental sampling was performed in 14 studies, nine of which detected P. aeruginosa. The risk factors identified were antimicrobial drug use and the number of days of antimicrobial therapy prescribed before positive blood culture, exposure to particular healthcare workers (HCW), transfusion of blood products, and intravenous delivery of nutrients/electrolytes. Exposure to umbilical venous catheters was associated with bloodstream infections. Increasing age and use of artificial fingernails were risk factors for colonization of hands of HCWs. Low birth weight pre-term infants were at greater risk of mortality from P. aeruginosa infection than older infants.

10.1099/jmm.0.044818-0

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Identification of Invasive Serotype 1 Pneumococcal Isolates That Express Nonhemolytic Pneumolysin

Journal of Clinical Microbiology (2006)

Lea‐Ann S. Kirkham Johanna M. Jefferies A. Kerr Jing Yu Stuart C. Clarke

ABSTRACT Recently, there has been an increase in invasive pneumococcal disease (IPD) caused by serotype 1 Streptococcus pneumoniae throughout Europe. Serotype 1 IPD is associated with bacteremia and pneumonia in Europe and North America, especially in neonates, and is ranked among the top five most prevalent pneumococcal serotypes in at least 10 countries. The currently licensed pediatric pneumococcal vaccine does not afford protection to this serotype. Upon screening of 252 clinical isolates of S. pneumoniae , we discovered mutations in the pneumolysin gene of two out of the four serotype 1 strains present in the study group. Analysis of an additional 28 serotype 1 isolates from patients with IPD from various Scottish Health Boards, revealed that >50% had mutations in their pneumolysin genes. This resulted in the expression of nonhemolytic forms of pneumolysin. All of the strains producing nonhemolytic pneumolysin were sequence type 306 (ST306), whereas those producing “wild-type” pneumolysin were ST227. The mutations were in a region of pneumolysin involved in pore formation. These mutations can be made in vitro to give the nonhemolytic phenotype. Pneumolysin is generally conserved throughout all serotypes of S. pneumoniae and is essential for full invasive disease; however, it appears that serotype 1 ST306 does not require hemolytically active pneumolysin to cause IPD.

Pneumolysin

Pneumococcal infections

10.1128/jcm.44.1.151-159.2006

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Potential Impact of Conjugate Vaccine on the Incidence of Invasive Pneumococcal Disease among Children in Scotland

Journal of Clinical Microbiology (2006)

Stuart C. Clarke Johanna M. Jefferies Andrew Smith Jim McMenamin Timothy J. Mitchell

ABSTRACT We sought to determine the potential impact of seven-valent pneumococcal conjugate vaccine on the incidence of invasive pneumococcal disease (IPD) among children in Scotland. Invasive pneumococci from blood and cerebrospinal fluid, isolated between 2000 and 2004 from all children aged less than 5 years in Scotland, were characterized by serotyping. Using reported efficacy data of the seven-valent pneumococcal conjugate vaccine (PCV7) along with likely coverage rates, we made an estimation of the potential impact on the incidence of IPD among children in Scotland. A total of 217 pneumococci were characterized into 22 different serogroups/types, the most common, in rank order, being 14, 19F, 6B, 18C, 23F, 9V, 4, 1, 19A, and 6A. Estimated serotype coverage for PCV7 was 76.5% in those aged less than 5 years of age but increased to 88.9% for those aged 1 year. By using serotype coverage and estimates of vaccine efficacy and uptake, the potential impact of the vaccine for those greater than 2 months of age, but less than 5 years, was estimated as 67.3%, leading to an average of 29 preventable cases per year. The introduction of PCV7 into the childhood immunization schedule would reduce the burden of pneumococcal disease in children, and the incidence would be particularly reduced in those children aged 1 year. Additional benefits may be gained in adults through herd protection. Continued surveillance of IPD is required before, during, and after the introduction of PCV7.

Pneumococcal Conjugate Vaccine

Pneumococcal infections

Herd Immunity

Pneumococcal vaccine

10.1128/jcm.44.4.1224-1228.2006

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Citations (15)

Identification of a Secreted Cholesterol-Dependent Cytolysin (Mitilysin) from Streptococcus mitis

Journal of Bacteriology (2006)

Johanna M. Jefferies Leena Nieminen Lea‐Ann S. Kirkham Calum Johnston A. Gordon Smith

We have detected a cholesterol-dependent cytolysin, which we have named mitilysin, in a small number of Streptococcus mitis isolates. We have sequenced the mitilysin gene from seven isolates of S. mitis. Comparisons with the pneumococcal pneumolysin gene show 15 amino acid substitutions. S. mitis appear to release mitilysin extracellularly. Certain alleles of mitilysin are not recognized by a monoclonal antibody raised to the related toxin pneumolysin. Based on enzyme-linked immunosorbent assay and neutralization assay results, one isolate of S. mitis may produce a further hemolytic toxin in addition to mitilysin. As genetic exchange is known to occur between S. mitis and Streptococcus pneumoniae, this finding may have implications for the development of vaccines or therapies for pneumococcal disease that are based on pneumolysin.

Cytolysin

Streptococcus mitis

Identification

Streptococcus intermedius

10.1128/jb.01092-06

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Citations (37)

Evaluation of swabbing methods for estimating the prevalence of bacterial carriage in the upper respiratory tract: a cross sectional study

BMJ Open (2014)

Abigail L. Coughtrie Robert Whittaker Nelupha Begum Rebecca Anderson Andrew Tuck

Objectives Bacterial carriage in the upper respiratory tract is usually asymptomatic but can lead to respiratory tract infection (RTI), meningitis and septicaemia. We aimed to provide a baseline measure of Streptococcus pneumoniae , Moraxella catarrhalis , Pseudomonas aeruginosa , Staphylococcus aureus , Haemophilus influenzae and Neisseria meningitidis carriage within the community. Self-swabbing and healthcare professional (HCP) swabbing were compared. Design Cross-sectional study. Setting Individuals registered at 20 general practitioner practices within the Wessex Primary Care Research Network South West, UK. Participants 10 448 individuals were invited to participate; 5394 within a self-swabbing group and 5054 within a HCP swabbing group. Self-swabbing invitees included 2405 individuals aged 0–4 years and 3349 individuals aged ≥5 years. HCP swabbing invitees included 1908 individuals aged 0–4 years and 3146 individuals aged ≥5 years. Results 1574 (15.1%) individuals participated, 1260 (23.4%, 95% CI 22.3% to 24.5%) undertaking self-swabbing and 314 (6.2%, 95% CI 5.5% to 6.9%) undertaking HCP-led swabbing. Participation was lower in young children and more deprived practice locations. Swab positivity rates were 34.8% (95% CI 32.2% to 37.4%) for self-taken nose swabs (NS), 19% (95% CI 16.8% to 21.2%) for self-taken whole mouth swabs (WMS), 25.2% (95% CI 20.4% to 30%) for nasopharyngeal swabs (NPS) and 33.4% (95% CI 28.2% to 38.6%) for HCP-taken WMS. Carriage rates of S. aureus were highest in NS (21.3%). S. pneumoniae carriage was highest in NS (11%) and NPS (7.4%). M. catarrhalis carriage was highest in HCP-taken WMS (28.8%). H. influenzae and P. aeruginosa carriage were similar between swab types. N. meningitidis was not detected in any swab. Age and recent RTI affected carriage of S. pneumoniae and H. influenzae . Participant costs were lower for self-swabbing (£41.21) versus HCP swabbing (£69.66). Conclusions Higher participation and lower costs of self-swabbing as well as sensitivity of self-swabbing favour this method for use in large population-based respiratory carriage studies.

Carriage

Cross-sectional study

Respiratory tract

10.1136/bmjopen-2014-005341

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Citations (31)