Roles of Oxygen and Photoinduced Acidification in the Light-Dependent Antiviral Activity of Hypocrellin A

Hypocrellin A displays photoinduced antiviral activity, in particular against the human immunodeficiency virus (HIV), as does its counterpart, hypericin. Although hypocrellin A, like hypericin, executes an excited-state intramolecular proton transfer, it differs from hypericin in two important ways. Unlike hypericin, hypocrellin A absolutely requires oxygen for its antiviral activity. Also, whereas we have previously demonstrated that hypericin functions as a light-induced proton source, we do not observe that hypocrellin A acidifies its surrounding medium in the presence of light. These results are discussed in the context of the ground- and excited-state photophysics of hypericin and its mechanisms of photoinduced virucidal activity

Research at the Interface between Chemistry and Virology: Development of a Molecular Flashlight

Although industrial researchers have been involved in interdisciplinary studies pertaining to virology for several decades, the participation of academic chemists has been significantly increased owing to the importance of HIV (human immunodeficiency virus), the virus which leads to the onset of AIDS (acquired immune deficiency syndrome). The Center for Disease Control estimates that almost 20 million people have been infected by HIV worldwide. The compelling need for effective antiviral therapies for HIVinfected persons, together with rapid advances in understanding the molecular mechanisms of virus replication, has resulted in an explosion of interest in antiviral agents and approaches to antiviral therapie

Complete Genome Sequence of the Avian Pathogenic Escherichia coli Strain APEC O78

Colibacillosis, caused by avian pathogenic Escherichia coli (APEC), is a significant disease, causing extensive animal and financial losses globally. Because of the significance of this disease, more knowledge is needed regarding APEC\u27s mechanisms of virulence. Here, we present the fully closed genome sequence of a typical avian pathogenic E. coli strain belonging to the serogroup O78

Escherichia coli, Salmonella, and Mycobacterium avium subsp. paratuberculosis in Wild European Starlings at a Kansas Cattle Feedlot

The prevalence of Escherichia coli, Salmonella spp., and Mycobacterium avium subsp.paratuberculosis isolated from the feces of wild European starlings (Sturnus vulgaris) humanely trapped at a feedlot in central Kansas was assessed. All E. coli and Salmonellaisolates recovered were tested for antimicrobial susceptibility using National Antimicrobial Resistance Monitoring System panels and the E. coli isolates were classified as to their content of genes associated with pathogenic E. coli of birds and cattle, including cvaC, iroN2, ompTp, hlyF2, eitC, iss, iutA, ireA, papC, stxI, stxII, sta, K99, F41, and eae.Escherichia coli O157:H7 and Mycobacterium avium subsp. paratuberculosis were not detected and Salmonella was isolated from only three samples, two of which displayed antimicrobial resistance. Approximately half of the E. coli isolates were resistant to antimicrobial agents with 96% showing resistance to tetracycline. Only one isolate was positive for a single gene associated with bovine pathogenic E. coli. An interesting finding of this study was that 5% of the E. coli isolates tested met the criteria established for identification as avian pathogenic E. coli (APEC). Thus these findings suggest that starlings are not a significant source of Salmonella spp., Mycobacterium avium subsp.paratuberculosis, E. coli O157, or other shiga toxin–producing E. coli in this feedlot. However, they may have the potential to spread APEC, an important pathogen of poultry and a potential pathogen to human beings

tkt1, located on a novel pathogenicity island, is prevalent in avian and human extraintestinal pathogenic Escherichia coli

<p>Abstract</p> <p>Background</p> <p>Extraintestinal pathogenic <it>Escherichia coli </it>are important pathogens of human and animal hosts. Some human and avian extraintestinal pathogenic <it>E. coli </it>are indistinguishable on the basis of diseases caused, multilocus sequence and phylogenetic typing, carriage of large virulence plasmids and traits known to be associated with extraintestinal pathogenic <it>E. coli </it>virulence.</p> <p>Results</p> <p>The gene <it>tkt1 </it>identified by a previous signature-tagged transposon mutagenesis study, was found on a 16-kb genomic island of avian pathogenic <it>Escherichia coli </it>(APEC) O1, the first pathogenic <it>Escherichia coli </it>strain whose genome has been completely sequenced. <it>tkt1 </it>was present in 39.6% (38/96) of pathogenic <it>Escherichia coli </it>strains, while only 6.25% (3/48) of <it>E. coli </it>from the feces of apparently healthy chickens was positive. Further, <it>tkt1 </it>was predominantly present in extraintestinal pathogenic <it>E. coli </it>belonging to the B2 phylogenetic group, as compared to extraintestinal pathogenic <it>E. coli </it>of other phylogenetic groups. The <it>tkt1</it>-containing genomic island is inserted between the <it>metE </it>and <it>ysgA </it>genes of the <it>E. coli </it>K12 genome. Among different extraintestinal pathogenic <it>E. coli </it>of the B2 phylogenetic group, 61.7% of pathogenic <it>Escherichia coli</it>, 80.6% of human uropathogenic <it>E.coli </it>and 94.1% of human neonatal meningitis-causing <it>E. coli</it>, respectively, harbor a complete copy of this island; whereas, only a few avian fecal <it>E. coli </it>strains contained the complete island. Functional analysis showed that Tkt1 confers very little transketolase activity but is involved in peptide nitrogen metabolism.</p> <p>Conclusion</p> <p>These results suggest <it>tkt1 </it>and its corresponding genomic island are frequently associated with avian and human ExPEC and are involved in bipeptide metabolism.</p

Genotypic and Phenotypic Traits That Distinguish Neonatal Meningitis-Associated Escherichia coli from Fecal E. coli Isolates of Healthy Human Hosts

Neonatal meningitis Escherichia coli (NMEC) is one of the top causes of neonatal meningitis worldwide. Here, 85 NMEC and 204 fecal E. coli isolates from healthy humans (HFEC) were compared for possession of traits related to virulence, antimicrobial resistance, and plasmid content. This comparison was done to identify traits that typify NMEC and distinguish it from commensal strains to refine the definition of the NMEC subpathotype, identify traits that might contribute to NMEC pathogenesis, and facilitate choices of NMEC strains for future study. A large number of E. coli strains from both groups were untypeable, with the most common serogroups occurring among NMEC being O18, followed by O83, O7, O12, and O1. NMEC strains were more likely than HFEC strains to be assigned to the B2 phylogenetic group. Few NMEC or HFEC strains were resistant to antimicrobials. Genes that best discriminated between NMEC and HFEC strains and that were present in more than 50% of NMEC isolates were mainly from extraintestinal pathogenic E. coli genomic and plasmid pathogenicity islands. Several of these defining traits had not previously been associated with NMEC pathogenesis, are of unknown function, and are plasmid located. Several genes that had been previously associated with NMEC virulence did not dominate among the NMEC isolates. These data suggest that there is much about NMEC virulence that is unknown and that there are pitfalls to studying single NMEC isolates to represent the entire subpathotype

Comparison of Extraintestinal Pathogenic Escherichia coli Strains from Human and Avian Sources Reveals a Mixed Subset Representing Potential Zoonotic Pathogens

Since extraintestinal pathogenic Escherichia coli (ExPEC) strains from human and avian hosts encounter similar challenges in establishing infection in extraintestinal locations, they may share similar contents of virulence genes and capacities to cause disease. In the present study, 1,074 ExPEC isolates were classified by phylogenetic group and possession of 67 other traits, including virulence-associated genes and plasmid replicon types. These ExPEC isolates included 452 avian pathogenic E. coli strains from avian colibacillosis, 91 neonatal meningitis E. coli (NMEC) strains causing human neonatal meningitis, and 531 uropathogenic E. coli strains from human urinary tract infections. Cluster analysis of the data revealed that most members of each subpathotype represent a genetically distinct group and have distinguishing characteristics. However, a genotyping cluster containing 108 ExPEC isolates was identified, heavily mixed with regard to subpathotype, in which there was substantial trait overlap. Many of the isolates within this cluster belonged to the O1, O2, or O18 serogroup. Also, 58% belonged to the ST95 multilocus sequence typing group, and over 90% of them were assigned to the B2 phylogenetic group typical of human ExPEC strains. This cluster contained strains with a high number of both chromosome- and plasmid-associated ExPEC genes. Further characterization of this ExPEC subset with zoonotic potential urges future studies exploring the potential for the transmission of certain ExPEC strains between humans and animals. Also, the widespread occurrence of plasmids among NMEC strains and members of the mixed cluster suggests that plasmid-mediated virulence in these pathotypes warrants further attention

A Novel Two-Component Signaling System Facilitates Uropathogenic Escherichia coli\u27s Ability to Exploit Abundant Host Metabolites

wo-component signaling systems (TCSs) are major mechanisms by which bacteria adapt to environmental conditions. It follows then that TCSs would play important roles in the adaptation of pathogenic bacteria to host environments. However, no pathogen-associated TCS has been identified in uropathogenic Escherichia coli (UPEC). Here, we identified a novel TCS, which we termed KguS/KguR (KguS: α-ketoglutarate utilization sensor; KguR: α-ketoglutarate utilizationregulator) in UPEC CFT073, a strain isolated from human pyelonephritis. kguS/kguR was strongly associated with UPEC but was found only rarely among other E. coli including commensal and intestinal pathogenic strains. An in vivo competition assay in a mouse UTI model showed that deletion of kguS/kguR in UPEC CFT073 resulted in a significant reduction in its colonization of the bladders and kidneys of mice, suggesting that KguS/KguR contributed to UPEC fitness in vivo. Comparative proteomics identified the target gene products of KguS/KguR, and sequence analysis showed that TCS KguS/KguR and its targeted-genes,c5032 to c5039, are encoded on a genomic island, which is not present in intestinal pathogenicE. coli. Expression of the target genes was induced by α-ketoglutarate (α-KG). These genes were further shown to be involved in utilization of α-KG as a sole carbon source under anaerobic conditions. KguS/KguR contributed to the regulation of the target genes with the direct regulation by KguR verified using an electrophoretic mobility shift assay. In addition, oxygen deficiency positively modulated expression of kguS/kguR and its target genes. Taken altogether, this study describes the first UPEC-associated TCS that functions in controlling the utilization of α-ketoglutarate in vivo thereby facilitating UPEC adaptation to life inside the urinary tract

Comparative Analysis of Phylogenetic Assignment of Human and Avian ExPEC and Fecal Commensal Escherichia coli Using the (Previous and Revised) Clermont Phylogenetic Typing Methods and its Impact on Avian Pathogenic Escherichia coli (APEC) Classification

The Clermont scheme has been used for subtyping of Escherichia coli since it was initially described in early 2000. Since then, researchers have used the scheme to type and sub-type commensal E. coli and pathogenic E. coli, such as extraintestinal pathogenic E. coli (ExPEC), and compare their phylogenetic assignment by pathogenicity, serogroup, distribution among ExPEC of different host species and complement of virulence and resistance traits. Here, we compare assignments of human and avian ExPEC and commensal E. coli using the old and revised Clermont schemes to determine if the new scheme provides a refined snapshot of isolate classification. 1,996 E. coli from human hosts and poultry, including 84 human neonatal meningitis E. coli isolates, 88 human vaginal E. coli, 696 human uropathogenic E. coli, 197 healthy human fecal E. coli, 452 avian pathogenic E. coli (APEC), 200 retail poultry E. coli, 80 crop and gizzard E. coli from healthy poultry at slaughter and 199 fecal E. coli from healthy birds at slaughter. All isolates were subject to phylogenetic analysis using the Clermont et al. (2000, 2013) schemes and compared to determine the effect of the new classification on strain designation. Most of the isolates’ strain designation remained where they were originally assigned. Greatest designation change occurred in APEC where 53.8% of isolates were reclassified; while classification rates among human strains ranged from 8 to 14%. However, some significant changes were observed for UPEC associated strains with significant (P < 0.05) designation changes observed from A to C and D to E or F phylogenetic types; a similar designation change was noted among NMEC for D to F designation change. Among the APEC significant designation changes were observed from A to C and D to E and F. These studies suggest that the new scheme provides a tighter and more meaningful definition of some ExPEC; while the new typing scheme has a significant impact on APEC classification. A comparison of phylogenetic group assignment by content of virulence, resistance, replicon and pathogenicity island genes in APEC suggests that insertion of pathogenicity islands into the genome appears to correlate closely with revised phylogenetic assignment.This article is published as Logue, Catherine M., Yvonne Wannemuehler, Bryon A. Nicholson, Curt Doetkott, Nicolle L. Barbieri, and Lisa K. Nolan. "Comparative analysis of phylogenetic assignment of human and avian ExPEC and fecal commensal Escherichia coli using the (previous and revised) Clermont phylogenetic typing methods and its impact on avian pathogenic Escherichia coli (APEC) classification." Frontiers in Microbiology 8 (2017): 283. DOI: 10.3389/fmicb.2017.00283. Copyright 2017 Logue, Wannemuehler, Nicholson, Doetkott, Barbieri and Nolan. Attribution 4.0 International (CC BY 4.0). Posted with permission

Associations Between Multidrug Resistance, Plasmid Content, and Virulence Potential Among Extraintestinal Pathogenic and Commensal Escherichia coli from Humans and Poultry

The emergence of plasmid-mediated multidrug resistance (MDR) among enteric bacteria presents a serious challenge to the treatment of bacterial infections in humans and animals. Recent studies suggest that avianEscherichia coli commonly possess the ability to resist multiple antimicrobial agents, and might serve as reservoirs of MDR for human extraintestinal pathogenic Escherichia coli (ExPEC) and commensal E. coli populations. We determined antimicrobial susceptibility profiles for 2202 human and avian E. coli isolates, then sought for associations among resistance profile, plasmid content, virulence factor profile, and phylogenetic group. Avian-source isolates harbored greater proportions of MDR than their human counterparts, and avian ExPEC had higher proportions of MDR than did avian commensal E. coli. MDR was significantly associated with possession of the IncA/C, IncP1-α, IncF, and IncI1 plasmid types. Overall, inferred virulence potential did not correlate with drug susceptibility phenotype. However, certain virulence genes were positively associated with MDR, including ireA,ibeA, fyuA, cvaC, iss, iutA, iha, and afa. According to the total dataset, isolates segregated significantly according to host species and clinical status, thus suggesting that avian and human ExPEC and commensal E. coli represent four distinct populations with limited overlap. These findings suggest that in extraintestinal E. coli, MDR is most commonly associated with plasmids, and that these plasmids are frequently found among avian-source E. coli from poultry production systems