Publications by authors named "Peter W Andrew"

Efficient utilization of nutrients is crucial for microbial survival and virulence. The same nutrient may be utilized by multiple catabolic pathways, indicating that the physical and chemical environments for induction as well as their functional roles may differ. Here, we study the tagatose and Leloir pathways for galactose catabolism of the human pathogen Streptococcus pneumoniae.

View Article and Find Full Text PDF

The temperature can vary according to the host tissue and the response to infection. has evolved mechanisms to survive these temperature differences, but neither the consequences of different temperatures for pneumococcal phenotype nor the genetic basis of thermal adaptation are known in detail. In our previous study [16], we found that CiaR, which is a part of two-component regulatory system CiaRH, as well as 17 genes known to be controlled by CiaRH, were identified to be differentially expressed with temperature.

View Article and Find Full Text PDF

may inhabit the upper respiratory tract of humans without causing harm but it also causes diseases with high morbidity and mortality. It has excellent adaptive capabilities thanks to its ability to shuffle its genetic content by acquiring and incorporating DNA from other bacteria and is highly competent for genetic transformation. Sugar sensing, cleavage and transport ensure its fitness and survival in the host, and intracellular survival in macrophages has been linked to virulence.

View Article and Find Full Text PDF

Objectives: Knowledge of Acute Respiratory virus Infection (ARI) is limited in relation to their substantial global burden. We completed a feasibility study of a novel method to study the natural transmission of respiratory viruses from young children to adults in hospital.

Methods: Between September 2012 and May 2015, we recruited healthy adults (contacts) and paediatric inpatients with ARIs (index) presenting to the University Hospitals Leicester NHS Trust, Leicester, UK.

View Article and Find Full Text PDF

Circadian rhythms affect the progression and severity of bacterial infections including those caused by , but the mechanisms responsible for this phenomenon remain largely elusive. Following advances in our understanding of the role of replication of within splenic macrophages, we sought to investigate whether events within the spleen correlate with differential outcomes of invasive pneumococcal infection. Utilising murine invasive pneumococcal disease (IPD) models, here we report that infection during the murine active phase (zeitgeber time 15; 15h after start of light cycle, 3h after start of dark cycle) resulted in significantly faster onset of septicaemia compared to rest phase (zeitgeber time 3; 3h after start of light cycle) infection.

View Article and Find Full Text PDF

Exposure to particulate matter (PM), a major component of air pollution, is associated with exacerbation of chronic respiratory disease, and infectious diseases such as community-acquired pneumonia. Although PM can cause adverse health effects through direct damage to host cells, our previous study showed that PM can also impact bacterial behaviour by promoting in vivo colonization. In this study we describe the genetic mechanisms involved in the bacterial response to exposure to black carbon (BC), a constituent of PM found in most sources of air pollution.

View Article and Find Full Text PDF

Bacteria have evolved mechanisms which enable them to control intracellular concentrations of metals. In the case of transition metals, such as copper, iron and zinc, bacteria must ensure enough is available as a cofactor for enzymes whilst at the same time preventing the accumulation of excess concentrations, which can be toxic. Interestingly, metal homeostasis and resistance systems have been found to play important roles in virulence.

View Article and Find Full Text PDF

Background: Hypervirulent (hv) strains of capsule type K1 and K2 cause invasive infections associated with hepatic abscesses, which can be difficult to treat and are frequently associated with relapsing infections. Other strains (non-hv), including lineages that have acquired carbapenem resistance, do not manifest this pathology. In this work we aimed to test the hypothesis that within-macrophage replication is a key mechanism underpinning abscess formation in hv infections.

View Article and Find Full Text PDF

Background: Severe community-acquired pneumococcal pneumonia is commonly associated with bacteraemia. Although it is assumed that the bacteraemia solely derives from pneumococci entering the blood from the lungs it is unknown if other organs are important in the pathogenesis of bacteraemia. Using three models, we tested the relevance of the spleen in pneumonia-associated bacteraemia.

View Article and Find Full Text PDF

During its progression from the nasopharynx to other sterile and nonsterile niches of its human host, Streptococcus pneumoniae must cope with changes in temperature. We hypothesized that the temperature adaptation is an important facet of pneumococcal survival in the host. Here, we evaluated the effect of temperature on pneumococcus and studied the role of glutamate dehydrogenase (GdhA) in thermal adaptation associated with virulence and survival.

View Article and Find Full Text PDF

Rggs are a group of transcriptional regulators with diverse roles in metabolism and virulence. Here, we present work on the Rgg1518/SHP1518 quorum sensing system of Streptococcus pneumoniae. The activity of Rgg1518 is induced by its cognate peptide, SHP1518.

View Article and Find Full Text PDF

Streptococcus pneumoniae is a major human pathogen, causing pneumonia and sepsis. Genetic components strongly influence host responses to pneumococcal infections, but the responsible loci are unknown. We have previously identified a locus on mouse chromosome 7 from a susceptible mouse strain, CBA/Ca, to be crucial for pneumococcal infection.

View Article and Find Full Text PDF

Oligomers of pneumolysin form transmembrane channels in cholesterol-containing lipid bilayers. The mechanism of pore formation involves a multistage process in which the protein, at first, assembles into a ring-shaped complex on the outer-bilayer leaflet. In a subsequent step, the complex inserts into the membrane.

View Article and Find Full Text PDF

is able to cause deadly diseases by infecting different tissues, each with distinct environmental and nutritional compositions. We hypothesize that the adaptive capabilities of the microbe is an important facet of pneumococcal survival in fluctuating host environments. Quorum-sensing (QS) mechanisms are pivotal for microbial host adaptation.

View Article and Find Full Text PDF

Complement is a critical component of antimicrobial immunity. Various complement regulatory proteins prevent host cells from being attacked. Many pathogens have acquired the ability to sequester complement regulators from host plasma to evade complement attack.

View Article and Find Full Text PDF

Microbes communicate with each other by using quorum sensing (QS) systems and modulate their collective 'behavior' for in-host colonization and virulence, biofilm formation, and environmental adaptation. The recent increase in genome data availability reveals the presence of several putative QS sensing circuits in microbial pathogens, but many of these have not been functionally characterized yet, despite their possible utility as drug targets. To increase the repertoire of functionally characterized QS systems in bacteria, we studied Rgg144/Shp144 and Rgg939/Shp939, two putative QS systems in the important human pathogen Streptococcus pneumoniae.

View Article and Find Full Text PDF

Bacterial septicaemia is a major cause of mortality, but its pathogenesis remains poorly understood. In experimental pneumococcal murine intravenous infection, an initial reduction of bacteria in the blood is followed hours later by a fatal septicaemia. These events represent a population bottleneck driven by efficient clearance of pneumococci by splenic macrophages and neutrophils, but as we show in this study, accompanied by occasional intracellular replication of bacteria that are taken up by a subset of CD169 splenic macrophages.

View Article and Find Full Text PDF

Excess copper is highly toxic and forms part of the host innate immune system's antibacterial arsenal, accumulating at sites of infection and acting within macrophages to kill engulfed pathogens. We show for the first time that a novel, horizontally gene transferred copper resistance locus (copXL), uniquely associated with the SCCmec elements of the highly virulent, epidemic, community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) USA300, confers copper hyper-resistance. These genes are additional to existing core genome copper resistance mechanisms, and are not found in typical S.

View Article and Find Full Text PDF

We describe the development, characterization, and biological testing of a new type of linear molecularly imprinted polymer (LMIP) designed to act as an anti-infective by blocking the quorum sensing (QS) mechanism and so abrogating the virulence of the pathogen Streptococcus pneumoniae. The LMIP is prepared (polymerized) in presence of a template molecule, but unlike in traditional molecular imprinting approaches, no cross-linker is used. This results in soluble low-molecular-weight oligomers that can act as a therapeutic agent in vitro and in vivo.

View Article and Find Full Text PDF

A spectroscopic technique is presented that is able to identify rapid changes in the bending modulus and fluidity of vesicle lipid bilayers on the micrometer scale, and distinguish between the presence and absence of heterogeneities in lipid-packing order. Individual unilamellar vesicles have been isolated using laser tweezers and, by measuring the intensity modulation of elastic back-scattered light, changes in the biophysical properties of lipid bilayers were revealed. Our approach offers unprecedented temporal resolution and, uniquely, physical transformations of lipid bilayers can be monitored on a length scale of micrometers.

View Article and Find Full Text PDF

is a foodborne pathogen responsible for a number of life-threatening infections of humans. During an infection, it invades epithelial cells before spreading from the intestine to the cells of the liver and spleen. This requires an ability to adapt to varying oxygen levels.

View Article and Find Full Text PDF

In this study, the intestinal microbial proteome of children with established type 1 diabetes (T1D) was compared with the proteome of healthy children (Control) with the aim to identify differences in the activity of the intestinal microbiota that not only will contribute to a deeper knowledge of the functionality of the gut in these children but also may provide new approaches to improve the control of the disease. Faecal protein extracts collected from three T1D children (aged 9.3±0.

View Article and Find Full Text PDF

Pneumococcal neuraminidase is a key enzyme for sequential deglycosylation of host glycans, and plays an important role in host survival, colonization, and pathogenesis of infections caused by Streptococcus pneumoniae. One of the factors that can affect the activity of neuraminidase is the amount and position of acetylation present in its substrate sialic acid. We hypothesised that pneumococcal esterases potentiate neuraminidase activity by removing acetylation from sialic acid, and that will have a major effect on pneumococcal survival on mucin, colonization, and virulence.

View Article and Find Full Text PDF

Catabolism of galactose by Streptococcus pneumoniae alters the microbe's metabolism from homolactic to mixed acid fermentation, and this shift is linked to the microbe's virulence. However, the genetic basis of this switch is unknown. Pyruvate formate lyase (PFL) is a crucial enzyme for mixed acid fermentation.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: