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Richard Moxon

Publications and source records attributed to Richard Moxon.

7 recordsLinked to original sources
PubMed2006

Bacterial contingency loci: the role of simple sequence DNA repeats in bacterial adaptation.

Bacterial pathogens face stringent challenges to their survival because of the many unpredictable, often precipitate, and dynamic changes that occur in the host environment or in the process of transmission from one host to another. Bacterial adaptation to their hosts involves either a mechanism for sensing and responding to external changes or the selection of variants that arise through mutation. Here we review how bacterial pathogens exploit localized hypermutation, through polymerase slippage of simple sequence repeats (SSRs), to generate phenotypic variation and enhanced fitness. These SSRs are located within the reading frame or in the promoter of a subset of genes, often termed contingency loci, whose functions are usually involved in direct interactions with host structures.

Adaptation, Physiological↗
PubMed2005

Sialic acid transport in Haemophilus influenzae is essential for lipopolysaccharide sialylation and serum resistance and is dependent on a novel tripartite ATP-independent periplasmic transporter.

Sialylation of the lipopolysaccharide (LPS) is an important mechanism used by the human pathogen Haemophilus influenzae to evade the innate immune response of the host. We have demonstrated that N-acetylneuraminic acid (Neu5Ac or sialic acid) uptake in H. influenzae is essential for the subsequent modification of the LPS and that this uptake is mediated through a single transport system which is a member of the tripartite ATP-independent periplasmic (TRAP) transporter family. Disruption of either the siaP (HI0146) or siaQM (HI0147) genes, that encode the two subunits of this transporter, results in a complete loss of uptake of [14C]-Neu5Ac. Mutant strains lack sialylated glycoforms in their LPS and are more sensitive to killing by human serum than the parent strain. The SiaP protein has been purified and demonstrated to bind a stoichiometric amount of Neu5Ac by electrospray mass spectrometry. This binding was of high affinity with a Kd of approximately 0.1 microM as determined by protein fluorescence. The inactivation of the SiaPQM TRAP transporter also results in decreased growth of H. influenzae in a chemically defined medium containing Neu5Ac, supporting an additional nutritional role of sialic acid in H. influenzae physiology.

Bacterial Proteins↗
PubMed2004

Adult mesoblastic nephroma: appearances on magnetic resonance imaging.

Mesoblastic nephroma presenting in an adult is extremely unusual. The magnetic resonance imaging (MRI) appearances of this tumor in adulthood have not been widely reported. We present a 55-year-old patient who was diagnosed with this rare neoplasm and describe the MRI findings.

Diagnosis, Differential↗
PubMed2004

Outbreak of Haemophilus influenzae type b disease among fully vaccinated children in a day-care center.

BACKGROUND: Two cases of invasive Haemophilus influenzae type b (Hib) infection were reported in immunized children in a day nursery within 1 week. Both cases were younger than 18 months of age, cared for in the same room. We aimed to characterize carriage of Hib and response to eradication therapy in this setting. METHODS: Ninety-four children were enrolled in the nursery, cared for by 21 staff in 4 rooms, divided by age. Two children of a part time teacher also attended. Oropharyngeal swabs were taken to detect Hib carriage before introduction of rifampin prophylaxis (20 mg/kg/day for 4 days). A questionnaire addressing risk factors for colonization was administered to parents and staff. Carriage was reassessed in children and carers from the same room as the index cases 1 month later. RESULTS: Eighty-nine children and all 21 staff were swabbed. Two additional Hib carriers, 1 child and 1 staff member, were identified from the same room as the cases. These isolates appeared identical with those causing invasive disease. Given the small numbers no clear risk factors for carriage could be confirmed. Compliance with rifampin prophylaxis was 97.4%. One month later no carriers were found among the 7 children and 3 staff tested from the room in which the cases were originally identified. CONCLUSIONS: Although immunization against Hib has resulted in a reduction in the incidence of this disease in the UK, individual protection cannot be assumed to be infallible. The importance of timely chemoprophylaxis of close contacts of a child with invasive Hib disease is reinforced.

Bacterial Capsules↗
PubMed2002

The avian chorioallantoic membrane in ovo--a useful model for bacterial invasion assays.

The aim of this study was to evaluate the practicability of the chick embryo chorioallantoic membrane (CAM) with special regard to the 'natural air sac' technique (NAST) of preparation for in-vivo research on the invasive potential of bacterial strains of various enterobacterial species. It was sought to establish an experimental system more closely resembling in-vivo conditions than cell lines on one hand, and cheaper and easier to handle than established animal models on the other. Fertilized eggs of the domestic fowl were incubated. The CAM was prepared atraumatically at the natural air space of the egg, and a cannula was inserted for subsequent extraction of allantoic fluid (AF) below the CAM. The CAM was then inoculated with either one out of five strains of Klebsiella pneumoniae, an Escherichia coli K-12 strain or a Salmonella typhimurium strain, either alone or in combinations, respectively. AF samples were extracted at certain time points, and the presence of bacteria was determined by cultivation. Penetration and mortality ratios of the infected embryos were calculated. In addition, the mode of crossing the epithelial barrier was examined by electron microscopy. Differing rates of invasion through the CAM and rates of mortality of the chicken embryos demonstrated a clear dependency on the inoculated bacterial strain. Low invading bacteria could be distinguished from intermediate strains, and from strains exerting a strong capability of invasion and killing of the embryos. Simultaneous monotopical inoculation of Klebsiella and E. coli showed a permissive effect of co-incubated Klebsiella on the invasiveness of E. coli. The chick embryo CAM prepared by NAST has shown to be a useful model for in vivo studies on invasion capabilities, pathogenicity and interactions of inoculated bacteria.

Allantois↗
PubMed2002

Bacterial pathogen genomics and vaccines.

Infectious diseases remain a major cause of deaths and disabilities in the world, the majority of which are caused by bacteria. Although immunisation is the most cost effective and efficient means to control microbial diseases, vaccines are not yet available to prevent many major bacterial infections. Examples include dysentery (shigellosis), gonorrhoea, trachoma, gastric ulcers and cancer (Helicobacter pylori). Improved vaccines are needed to combat some diseases for which current vaccines are inadequate. Tuberculosis, for example, remains rampant throughout most countries in the world and represents a global emergency heightened by the pandemic of HIV. The availability of complete genome sequences has dramatically changed the opportunities for developing novel and improved vaccines and facilitated the efficiency and rapidity of their development. Complete genomic databases provide an inclusive catalogue of all potential candidate vaccines for any bacterial pathogen. In conjunction with adjunct technologies, including bioinformatics, random mutagenesis, microarrays, and proteomics, a systematic and comprehensive approach to identifying vaccine discovery can be undertaken. Genomics must be used in conjunction with population biology to ensure that the vaccine can target all pathogenic strains of a species. A proof in principle of the utility of genomics is provided by the recent exploitation of the complete genome sequence of Neisseria meningitidis group B.

Animals↗