The mechanism of action of pepR, a #viral-derived #peptide, against #Staphylococcus aureus #biofilms (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

The mechanism of action of pepR, a viral-derived peptide, against Staphylococcus aureus biofilms

Sandra N Pinto, Susana A Dias, Ana F Cruz, Dalila Mil-Homens, Fabio Fernandes, Javier Valle, David Andreu, Manuel Prieto, Miguel A R B Castanho, Ana Coutinho, Ana Salomé Veiga

Journal of Antimicrobial Chemotherapy, dkz223,

Published: 24 May 2019




To investigate the mechanism of action at the molecular level of pepR, a multifunctional peptide derived from the Dengue virus capsid protein, against Staphylococcus aureus biofilms.


Biofilm mass, metabolic activity and viability were quantified using conventional microbiology techniques, while fluorescence imaging methods, including a real-time calcein release assay, were employed to investigate the kinetics of pepR activity at different biofilm depths.


Using flow cytometry-based assays, we showed that pepR is able to prevent staphylococcal biofilm formation due to a fast killing of planktonic bacteria, which in turn resulted from a peptide-induced increase in the permeability of the bacterial membranes. The activity of pepR against pre-formed biofilms was evaluated through the application of a quantitative live/dead confocal laser scanning microscopy (CLSM) assay. The results show that the bactericidal activity of pepR on pre-formed biofilms is dose and depth dependent. A CLSM-based assay of calcein release from biofilm-embedded bacteria was further developed to indirectly assess the diffusion and membrane permeabilization properties of pepR throughout the biofilm. A slower diffusion and delayed activity of the peptide at deeper layers of the biofilm were quantified.


Overall, our results show that the activity of pepR on pre-formed biofilms is controlled by its diffusion along the biofilm layers, an effect that can be counteracted by an additional administration of peptide. Our study sheds new light on the antibiofilm mechanism of action of antimicrobial peptides, particularly the importance of their diffusion properties through the biofilm matrix on their activity.


Keywords: Antimicrobial peptides; Biofilm; Staphylococcus aureus.



Reduced #ceftazidime and #ertapenem susceptibility due to production of #OXA-2 in #Klebsiella pneumoniae ST258 (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Reduced ceftazidime and ertapenem susceptibility due to production of OXA-2 in Klebsiella pneumoniaeST258

Alina Iovleva, Roberta T Mettus, Christi L McElheny, Mustapha M Mustapha, Daria Van Tyne, Ryan K Shields, A William Pasculle, Vaughn S Cooper, Yohei Doi

Journal of Antimicrobial Chemotherapy, dkz183,

Published: 24 May 2019




OXA-2 is a class D β-lactamase that confers resistance to penicillins, as well as narrow-spectrum cephalosporins. OXA-2 was recently reported to also possess carbapenem-hydrolysing activity. Here, we describe a KPC-2-encoding Klebsiella pneumoniae isolate that demonstrated reduced susceptibility to ceftazidime and ertapenem due to production of OXA-2.


To elucidate the role of OXA-2 production in reduced ceftazidime and ertapenem susceptibility in a K. pneumoniae ST258 clinical isolate.


MICs were determined by the agar dilution method. WGS was conducted to identify and compare resistance genes between isolates. Expression of KPC-2 was quantified by quantitative RT–PCR and immunoblotting. OXA-2 was expressed in Escherichia coli TOP10, as well as in K. pneumoniae ATCC 13883, to define the relative contribution of OXA-2 in β-lactam resistance. Kinetic studies were conducted using purified OXA-2 enzyme.


K. pneumoniae 1761 belonged to ST258 and carried both blaKPC-2 and blaOXA-2. However, expression of blaKPC-2 was substantially reduced due to an IS1294insertion in the promoter region. K. pneumoniae 1761, K. pneumoniae ATCC 13883 and E. coli TOP10 carrying blaOXA-2-harbouring plasmids showed reduced susceptibility to ertapenem and ceftazidime, but meropenem, imipenem and cefepime were unaffected. blaOXA-2 was carried on a 2910 bp partial class 1 integron containing aacA4-blaOXA-2-qacEΔ1-sul1 on an IncA/C2plasmid, which was not present in the earlier ST258 isolates possessing blaKPC-2 with intact promoters. Hydrolysis of ertapenem by OXA-2 was confirmed using purified enzyme.


Production of OXA-2 was associated with reduced ceftazidime and ertapenem susceptibility in a K. pneumoniae ST258 isolate.


© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email:

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (

Keywords: Antibiotics; Drugs Resistance; Beta-lactams; Carbapenem; Ceftazidime; Ertapenem; Meropenem; Imipenem; Cefepime.


#Prevalence and concentration of stx+ #Ecoli and E. coli O157 in #bovine #manure from #Florida #farms (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]


Prevalence and concentration of stx+ E. coli and E. coli O157 in bovine manure from Florida farms

Christopher A. Baker, Jaysankar De, Bruna Bertoldi, Laurel Dunn, Travis Chapin, Michele Jay-Russell, Michelle D. Danyluk, Keith R. Schneider

Published: May 24, 2019 / DOI:



Fresh produce outbreaks due to Shiga toxin-producing Escherichia coli (STEC) continue to occur in the United States (US). Manure-amended soils can pose a public health risk when used for growing raw agricultural commodities. Knowing the prevalence and concentration of STEC in untreated biological soil amendments of animal origin (BSAAO) is important to help guide the most appropriate pre-harvest interval(s) following application to limit risks from these soil amendments. Bovine manure samples were collected from 12 farms in Florida, including samples from piles, lagoons, barns, and screened solids. Two methods were used to detect stx1/2 and rfbE genes in samples. A prevalence rate of 9% for stx1 and/or stx2 and 19% for rfbE was observed from the 518 bovine manure samples evaluated. A most probable number (MPN) assay was performed on stx+ samples when applicable. The geometric mean for stx+samples (n = 20) was 3.37 MPN g-1 (0.53 log MPN g-1) with a maximum value of 6,800 MPN g-1 (3.83 log MPN g-1). This research was part of a larger nationwide geographical study on the prevalence and concentration of STEC in bovine manure to help guide regulations on feasible pre-harvest intervals for the application of untreated BSAAO.


Citation: Baker CA, De J, Bertoldi B, Dunn L, Chapin T, Jay-Russell M, et al. (2019) Prevalence and concentration of stx+ E. coli and E. coli O157 in bovine manure from Florida farms. PLoS ONE 14(5): e0217445.

Editor: P. Pardha-Saradhi, University of Delhi, INDIA

Received: March 18, 2019; Accepted: May 10, 2019; Published: May 24, 2019

Copyright: © 2019 Baker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: This work was supported by the Western Center for Food Safety contract U19-FD004995 from the U.S. Food and Drug Administration. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: E. Coli; Cattle; Environmental pollution; USA.


An #international #outbreak of #Salmonella enterica serotype Enteritidis linked to #eggs from #Poland: a microbiological and epidemiological study (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

An international outbreak of Salmonella enterica serotype Enteritidis linked to eggs from Poland: a microbiological and epidemiological study

Roan Pijnacker, MSc  *, Timothy J Dallman, PhD *, Aloys S L Tijsma, PhD, Gillian Hawkins, MBChB, Lesley Larkin, BVSc, Saara M Kotila, MSc, Giusi Amore, PhD, Ettore Amato, PhD, Pamina M Suzuki, MSc, Sarah Denayer, PhD, Sofieke Klamer, MSc, Judit Pászti, Jacquelyn McCormick, MPH, Hassan Hartman, PhD, Gareth J Hughes, PhD, Lin C T Brandal, PhD, Derek Brown, MSc, Joël Mossong, PhD, Cecilia Jernberg, PhD, Luise Müller, MSc, Daniel Palm, PhD, Ettore Severi, MSc, Joannna Gołębiowska, DVM, Blaženka Hunjak, PhD, Slawomir Owczarek, MSc, Simon Le Hello, PhD, Patricia Garvey, PhD, Kirsten Mooijman, MSc, Ingrid H M Friesema, PhD, Coen van der Weijden, BSc, Menno van der Voort, PhD, Valentina Rizzi, PhD, Eelco Franz, PhD on behalf of theInternational Outbreak Investigation Team †

Published: May 24, 2019 / DOI:




Salmonella spp are a major cause of food-borne outbreaks in Europe. We investigated a large multi-country outbreak ofSalmonella enterica serotype Enteritidis in the EU and European Economic Area (EEA).


A confirmed case was defined as a laboratory-confirmed infection with the outbreak strains of S Enteritidis based on whole-genome sequencing (WGS), occurring between May 1, 2015, and Oct 31, 2018. A probable case was defined as laboratory-confirmed infection withS Enteritidis with the multiple-locus variable-number tandem repeat analysis outbreak profile. Multi-country epidemiological, trace-back, trace-forward, and environmental investigations were done. We did a case-control study including confirmed and probable cases and controls randomly sampled from the population registry (frequency matched by age, sex, and postal code). Odds ratios (ORs) for exposure rates between cases and controls were calculated with unmatched univariable and multivariable logistic regression.


18 EU and EEA countries reported 838 confirmed and 371 probable cases. 509 (42%) cases were reported in 2016, after which the number of cases steadily increased. The case-control study results showed that cases more often ate in food establishments than did controls (OR 3·4 [95% CI 1·6–7·3]), but no specific food item was identified. Recipe-based food trace-back investigations among cases who ate in food establishments identified eggs from Poland as the vehicle of infection in October, 2016. Phylogenetic analysis identified two strains of S Enteritidis in human cases that were subsequently identified in salmonella-positive eggs and primary production premises in Poland, confirming the source of the outbreak. After control measures were implemented, the number of cases decreased, but increased again in March, 2017, and the increase continued into 2018.


This outbreak highlights the public health value of multi-country sharing of epidemiological, trace-back, and microbiological data. The re-emergence of cases suggests that outbreak strains have continued to enter the food chain, although changes in strain population dynamics and fewer cases indicate that control measures had some effect. Routine use of WGS in salmonella surveillance and outbreak response promises to identify and stop outbreaks in the future.


European Centre for Disease Prevention and Control; Directorate General for Health and Food Safety, European Commission; and National Public Health and Food Safety Institutes of the authors’ countries (see Acknowledgments for full list).

Keywords: Food Safety; EU; European Region; Samonella spp.


Immune-mediated #Drug-induced #Liver #Injury Caused by #Laninamivir Octanoate Hydrate: A Case Report (Intern Med., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Intern Med. 2019 May 22. doi: 10.2169/internalmedicine.2740-19. [Epub ahead of print]

Immune-mediated Drug-induced Liver Injury Caused by Laninamivir Octanoate Hydrate: A Case Report.

Kawaguchi T1, Arinaga-Hino T1, Shimizu M2, Tanikawa K3, Tokushige T4, Hirai S4, Nagamatsu H2, Tateishi H4, Takata A5, Ide T1, Torimura T1.

Author information: 1 Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Japan. 2 Department of Gastroenterology, Juntendo University School of Medicine, Japan. 3 Department of Diagnostic Pathology, Yame General Hospital, Japan. 4 Department of Gastroenterology, Yame General Hospital, Japan. 5 Department of Gastroenterology, Asakura Medical Association Hospital, Japan.



We herein report the first case of immune-mediated drug-induced liver injury that may have been caused by laninamivir. A 15-year-old girl was diagnosed with influenza and prescribed 40 mg laninamivir. Six weeks later, she was admitted to our hospital because of jaundice and fatigue. Laboratory examinations revealed elevated levels of hepatobiliary enzymes, and acute liver injury was suspected. Laboratory examinations and histological findings were characteristic of autoimmune hepatitis. Steroid treatment was ineffective, and azathioprine was added to the treatment. Twenty-two months after the onset, a second biopsy revealed the absence of inflammatory infiltrations, and the drugs were withdrawn. Liver function tests remained normal nine months after withdrawal.

KEYWORDS: autoimmune hepatitis; drug-induced autoimmune hepatitis; drug-induced liver injury; immune-mediated drug-induced liver injury; laninamivir

PMID: 31118398 DOI: 10.2169/internalmedicine.2740-19

Keywords: Antivirals; Drugs Safety; Laninamivir.


Boosting #Global #YellowFever #Vaccine #Supply for #Epidemic #Preparedness: 3 Actions for #China and the #USA (Virol Sin., abstract)

[Source: Virologica Sinica, full page: (LINK). Summary, edited.]

Boosting Global Yellow Fever Vaccine Supply for Epidemic Preparedness: 3 Actions for China and the USA

Authors: Daniel R. Lucey, Kristen R. Kent

Perspective / First Online: 24 May 2019


Yellow fever (YF) is an acute disease caused by a flavivirus that infects the liver. It can cause jaundice, bleeding, kidney damage, and death. No antiviral therapy exists. A vaccine does exist, however, and fortunately confers life-long immunity after a single dose (Monath et al.2016; WHO 2017a, b).




Compliance with Ethical Standards

Conflict of interest: The authors declare that they have no conflict of interest.

Animal and Human Rights Statement: This article does not contain any studies with human or animal subjects performed by any of the authors.

Keywords: Yellow Fever; Vaccines; USA; China.


#Marburg virus #RNA #synthesis is inhibited by a synthetic anti-VP35 #antibody (ACS Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

ACS Infect Dis. 2019 May 23. doi: 10.1021/acsinfecdis.9b00091. [Epub ahead of print]

Marburg virus RNA synthesis is inhibited by a synthetic anti-VP35 antibody.

Amatya P, Wagner N, Chen G, Luthra P, Shi L, Borek D, Pavlenco A, Rohrs HW, Basler CF, Sidhu SS, Gross ML, Leung DW.



Marburg virus causes sporadic outbreaks of severe hemorrhagic fever with high case fatality rates. Approved, effective, and safe therapeutic or prophylactic countermeasures are lacking. To address this, we used phage display to engineer a synthetic antibody, sFab H3, which binds the Marburg virus VP35 protein (mVP35). mVP35 is a critical cofactor of the viral replication complex and a viral immune antagonist. sFab H3 displayed high specificity for mVP35 and not for the closely related Ebola virus VP35. sFab H3 inhibited viral RNA synthesis in a minigenome assay, suggesting its potential use as an antiviral. We characterized sFab H3 by a combination of biophysical and biochemical methods, and a crystal structure of the complex solved to 1.7 Å resolution defined the molecular interface between sFab H3 and mVP35 interferon inhibitory domain. Our study identifies mVP35 as a therapeutic target using an approach that provides a framework for generating engineered Fabs targeting other viral proteins.

PMID: 31120240 DOI: 10.1021/acsinfecdis.9b00091

Keywords: Marburg virus; Monoclonal antibodies.