Differential Epigenetic Compatibility of qnr Antibiotic Resistance Determinants with the Chromosome of Escherichia coli

Environmental bacteria harbor a plethora of genes that, upon their horizontal transfer to new hosts, may confer resistance to antibiotics, although the number of such determinants actually acquired by pathogenic bacteria is very low. The founder effect, fitness costs and ecological connectivity all influence the chances of resistance transfer being successful. We examined the importance of these bottlenecks using the family of quinolone resistance determinants Qnr. The results indicate the epigenetic compatibility of a determinant with the host genome to be of great importance in the acquisition and spread of resistance. A plasmid carrying the widely distributed QnrA determinant was stable in Escherichia coli, whereas the SmQnr determinant was unstable despite both proteins having very similar tertiary structures. This indicates that the fitness costs associated with the acquisition of antibiotic resistance may not derive from a non-specific metabolic burden, but from the acquired gene causing specific changes in bacterial metabolic and regulatory networks. The observed stabilization of the plasmid encoding SmQnr by chromosomal mutations, including a mutant lacking the global regulator H-NS, reinforces this idea. Since quinolones are synthetic antibiotics, and since the origin of QnrA is the environmental bacterium Shewanella algae, the role of QnrA in this organism is unlikely to be that of conferring resistance. Its evolution toward this may have occurred through mutations or because of an environmental change (exaptation). The present results indicate that the chromosomally encoded Qnr determinants of S. algae can confer quinolone resistance upon their transfer to E. coli without the need of any further mutation. These results suggest that exaptation is important in the evolution of antibiotic resistance

A three-way comparative genomic analysis of Mannheimia haemolytica isolates

<p>Abstract</p> <p>Background</p> <p><it>Mannhemia haemolytica </it>is a Gram-negative bacterium and the principal etiological agent associated with bovine respiratory disease complex. They transform from a benign commensal to a deadly pathogen, during stress such as viral infection and transportation to feedlots and cause acute pleuropneumonia commonly known as shipping fever. The U.S beef industry alone loses more than one billion dollars annually due to shipping fever. Despite its enormous economic importance there are no specific and accurate genetic markers, which will aid in understanding the pathogenesis and epidemiology of <it>M. haemolytica </it>at molecular level and assist in devising an effective control strategy.</p> <p>Description</p> <p>During our comparative genomic sequence analysis of three <it>Mannheimia haemolytica </it>isolates, we identified a number of genes that are unique to each strain. These genes are "high value targets" for future studies that attempt to correlate the variable gene pool with phenotype. We also identified a number of high confidence single nucleotide polymorphisms (hcSNPs) spread throughout the genome and focused on non-synonymous SNPs in known virulence genes. These SNPs will be used to design new hcSNP arrays to study variation across strains, and will potentially aid in understanding gene regulation and the mode of action of various virulence factors.</p> <p>Conclusions</p> <p>During our analysis we identified previously unknown possible type III secretion effector proteins, clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated sequences (Cas). The presence of CRISPR regions is indicative of likely co-evolution with an associated phage. If proven functional, the presence of a type III secretion system in <it>M. haemolytica </it>will help us re-evaluate our approach to study host-pathogen interactions. We also identified various adhesins containing immuno-dominant domains, which may interfere with host-innate immunity and which could potentially serve as effective vaccine candidates.</p

CRISPR-based strategies in infectious disease diagnosis and therapy

CRISPR gene-editing technology has the potential to transform the diagnosis and treatment of infectious diseases, but most clinicians are unaware of its broad applicability. Derived from an ancient microbial defence system, these so-called "molecular scissors" enable precise gene editing with a low error rate. However, CRISPR systems can also be targeted against pathogenic DNA or RNA sequences. This potential is being combined with innovative delivery systems to develop new therapeutic approaches to infectious diseases.info:eu-repo/semantics/publishedVersio

A new species of Boehlkea (Characiformes: Characidae: Stevardiinae) from the rio Japurá, Amazon basin, Brazil

ABSTRACT A new species of Boehlkea is described from rio Japurá, Amazon basin. The new species differs from B. fredcochui by the presence of a vertically elongate humeral spot (vs. absence), complete lateral line (vs. incomplete), four rows of scales below lateral line (vs. three), and lower number of branched anal-fin rays (17-21 vs. 22-25), and from B. orcesi by the higher number of maxillary teeth (13-14 vs. 5-12), greater head length (27.9-29.9% vs. 24.3-27.5% of SL), and by the color pattern (basal half of dorsal-fin, distal portion of pelvic-fin, lower caudal-fin lobe and anal-fin with black chromatophores vs. absence of black chromatophores in the fins)

The Chlamydia psittaci Genome: A Comparative Analysis of Intracellular Pathogens

Chlamydiaceae are a family of obligate intracellular pathogens causing a wide range of diseases in animals and humans, and facing unique evolutionary constraints not encountered by free-living prokaryotes. To investigate genomic aspects of infection, virulence and host preference we have sequenced Chlamydia psittaci, the pathogenic agent of ornithosis.A comparison of the genome of the avian Chlamydia psittaci isolate 6BC with the genomes of other chlamydial species, C. trachomatis, C. muridarum, C. pneumoniae, C. abortus, C. felis and C. caviae, revealed a high level of sequence conservation and synteny across taxa, with the major exception of the human pathogen C. trachomatis. Important differences manifest in the polymorphic membrane protein family specific for the Chlamydiae and in the highly variable chlamydial plasticity zone. We identified a number of psittaci-specific polymorphic membrane proteins of the G family that may be related to differences in host-range and/or virulence as compared to closely related Chlamydiaceae. We calculated non-synonymous to synonymous substitution rate ratios for pairs of orthologous genes to identify putative targets of adaptive evolution and predicted type III secreted effector proteins.This study is the first detailed analysis of the Chlamydia psittaci genome sequence. It provides insights in the genome architecture of C. psittaci and proposes a number of novel candidate genes mostly of yet unknown function that may be important for pathogen-host interactions

Randomized trial to increase colorectal cancer screening in an ethnically diverse sample of first-degree relatives

BACKGROUND: Ethnic minorities, especially African Americans and Latinos, bear a disproportionate burden of colorectal cancer (CRC), as reflected in incidence, cancer stage, and mortality statistics. In all ethnic groups, first-degree relatives (FDRs) of CRC cases are at an elevated disease risk. However, underuse of CRC screening persists and is particularly evident among minority groups. The current study tested a stepped intervention to increase CRC screening among an ethnically diverse sample of FDRs of CRC cases. METHODS: A statewide cancer registry was used to recruit CRC cases and through them their FDRs. Relatives who were not current on CRC screening were randomized to intervention or usual-care control arms. The stepped intervention consisted of ethnically targeted and individually tailored print materials followed by telephone counseling for those unscreened at 6 months. RESULTS: The study sample of 1280 individuals consisted of 403 Latino, 284 African American, 242 Asian, and 351 white FDRs. Statistically significant effects were observed for the cumulative print plus telephone intervention at 12 months (26% in the intervention vs 18% in the control group) and the print intervention alone at 6 months (15% in the intervention vs 10% in the control group). The effect of the print intervention alone versus the cumulative interventions was not statistically significantly different. Stratified analyses indicated that the intervention was effective among white, Latino, and Asian individuals, but not among African-Americans. CONCLUSIONS: Overall, the intervention was effective in increasing screening rates. Oversampling racial/ethnic minorities allowed for the examination of effects within subgroups, revealing no effect among African American individuals. This finding illustrates the importance of including sufficient numbers of participants from diverse ethnic subgroups in intervention research to enable such stratified analyses. Cancer 2015;121:2951-2959

Neighborhood socio-economic disadvantage and race/ethnicity as predictors of breast cancer stage at diagnosis

Background: This study investigated the role of key individual- and community-level determinants to explore persisting racial/ethnic disparities in breast cancer stage at diagnosis in California during 1990 and 2000. Methods. We examined socio-demographic determinants and changes in breast cancer stage at diagnosis in California during 1990 and 2000. In situ, local, regional, and distant diagnoses were examined by individual (age, race/ethnicity, and marital status) and community (income and education by zip code) characteristics. Community variables were constructed using the California Cancer Registry 1990-2000 and the 1990 and 2000 U.S. Census. Results: From 1990 to 2000, there was an overall increase in the percent of in situ diagnoses and a significant decrease in regional and distant diagnoses. Among white and Asian/Pacific Islander women, a significant percent increase was observed for in situ diagnoses, and significant decreases in regional and distant diagnoses. Black women had a significant decrease in distant -stage diagnoses, and Hispanic women showed no significant changes in any diagnosis during this time period. The percent increase of in situ cases diagnosed between 1990 and 2000 was observed even among zip codes with low income and education levels. We also found a significant percent decrease in distant cases for the quartiles with the most poverty and least education. Conclusions: Hispanic women showed the least improvement in breast cancer stage at diagnosis from 1990 to 2000. Breast cancer screening and education programs that target under-served communities, such as the rapidly growing Hispanic population, are needed in California. © 2013 Flores et al.; licensee BioMed Central Ltd