#Reticulate #evolution is favored in #influenza #niche #switching (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Reticulate evolution is favored in influenza niche switching

Eric J. Ma a,1, Nichola J. Hill a, Justin Zabilansky a, Kyle Yuan a, and Jonathan A. Runstadler a,b,1

Author Affiliations: aDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; bDivision of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139

Edited by Edward F. DeLong, University of Hawaii at Manoa, Honolulu, HI, and approved March 30, 2016 (received for review December 4, 2015)



Are the processes that result in the exchange of genes between microbes quantitatively advantageous for those microbes when switching between ecological niches? To address this question, we consider the influenza A virus as a model microbe, with its ability to infect multiple host species (ecological niches) and undergo reassortment (exchange genes) with one another. Here, through our analysis of sequence data from the Influenza Research Database and the Barcode of Life Database, we find that the greater the quantitative difference between influenza hosts, the greater the proportion of reassortment events were found. More broadly, for microbes, we infer that reticulate evolutionary processes should be quantitatively favored when switching between ecological niches.



Reticulate evolution is thought to accelerate the process of evolution beyond simple genetic drift and selection, helping to rapidly generate novel hybrids with combinations of adaptive traits. However, the long-standing dogma that reticulate evolutionary processes are likewise advantageous for switching ecological niches, as in microbial pathogen host switch events, has not been explicitly tested. We use data from the influenza genome sequencing project and a phylogenetic heuristic approach to show that reassortment, a reticulate evolutionary mechanism, predominates over mutational drift in transmission between different host species. Moreover, as host evolutionary distance increases, reassortment is increasingly favored. We conclude that the greater the quantitative difference between ecological niches, the greater the importance of reticulate evolutionary processes in overcoming niche barriers.

ecology – reticulate evolution – influenza – host switch – reassortment



1To whom correspondence may be addressed. Email: jrun@mit.edu or ericmajinglong@gmail.com.

Author contributions: E.J.M. designed research; E.J.M. performed research; E.J.M. and J.Z. contributed new reagents/analytic tools; E.J.M., N.J.H., J.Z., K.Y., and J.A.R. analyzed data; and E.J.M., N.J.H., and J.A.R. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at http://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1522921113/-/DCSupplemental.

Keywords: Research; Abstracts; Influenza.


Use of post-exposure #prophylaxis after occupational #exposure to #Zaire #ebolavirus (Clin Infect Dis., abstract)

[Source: Clinical Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Use of post-exposure prophylaxis after occupational exposure to Zaire ebolavirus

Karen K. Wong1, Richard T. Davey Jr.2, Angela L. Hewlett3, Colleen S. Kraft4, Aneesh K. Mehta4, Mark J. Mulligan4, Allison Beck4, William Dorman5, Christopher J. Kratochvil3, Lilin Lai4, Tara N. Palmore2, Susan Rogers4, Philip W. Smith3, Anthony F. Suffredini6, Mark Wolcott5, Ute Ströher1, and Timothy M. Uyeki1

Author Affiliations: 1U.S. Centers for Disease Control and Prevention, Atlanta, Georgia, United States; 2National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States; 3University of Nebraska Medical Center, Omaha, Nebraska, United States; 4Emory University, Atlanta, Georgia, United States; 5US Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States; 6Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, United States

Corresponding author: Karen K. Wong, 1600 Clifton Rd NE, MS C-09, Atlanta, GA 30329; kwong@cdc.gov

Alternate corresponding author: Timothy M. Uyeki, 1600 Clifton Rd NE, MS A-20, Atlanta, GA 30329; tuyeki@cdc.gov



From September 2014–April 2015, six persons who had occupational exposures to Zaire ebolavirus in West Africa received investigational agents rVSV-ZEBOV or TKM-100802 for post-exposure prophylaxis and were monitored in the U.S. All patients experienced self-limited symptoms after PEP; none developed Ebola virus disease.

Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Keywords: Research; Abstracts; Ebola; Monoclonal Antibodies; Vaccines.


#Lack of #chicken #adaptation of newly emergent #Eurasian #H5N8 and reassortant #H5N2 HPAI #viruses in the #US is consistent with restricted #poultry #outbreaks … (Virology, abstract)

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

Virology. 2016 Apr 22;494:190-197. doi: 10.1016/j.virol.2016.04.019. [Epub ahead of print]

Lack of chicken adaptation of newly emergent Eurasian H5N8 and reassortant H5N2 high pathogenicity avian influenza viruses in the U.S. is consistent with restricted poultry outbreaks in the Pacific flyway during 2014-2015.

Bertran K1, Swayne DE2, Pantin-Jackwood MJ3, Kapczynski DR4, Spackman E5, Suarez DL6.

Author information: 1Exotic and Emerging Avian Viral Diseases Research Unit, Southeast Poultry Research Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, 934 College Station Rd, 30605 Athens, GA, USA. Electronic address: kateri.bertran@ars.usda.gov. 2Exotic and Emerging Avian Viral Diseases Research Unit, Southeast Poultry Research Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, 934 College Station Rd, 30605 Athens, GA, USA. Electronic address: david.swayne@ars.usda.gov. 3Exotic and Emerging Avian Viral Diseases Research Unit, Southeast Poultry Research Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, 934 College Station Rd, 30605 Athens, GA, USA. Electronic address: mary.pantin-jackwood@ars.usda.gov. 4Exotic and Emerging Avian Viral Diseases Research Unit, Southeast Poultry Research Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, 934 College Station Rd, 30605 Athens, GA, USA. Electronic address: darrell.kapczynski@ars.usda.gov. 5Exotic and Emerging Avian Viral Diseases Research Unit, Southeast Poultry Research Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, 934 College Station Rd, 30605 Athens, GA, USA. Electronic address: erica.spackman@ars.usda.gov. 6Exotic and Emerging Avian Viral Diseases Research Unit, Southeast Poultry Research Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, 934 College Station Rd, 30605 Athens, GA, USA. Electronic address: david.suarez@ars.usda.gov.



In 2014-2015, the U.S. experienced an unprecedented outbreak of Eurasian clade H5 highly pathogenic avian influenza (HPAI) virus, initially affecting mainly wild birds and few backyard and commercial poultry premises. To better model the outbreak, the pathogenesis and transmission dynamics of representative Eurasian H5N8 and reassortant H5N2 clade HPAI viruses detected early in the North American outbreak were investigated in chickens. High mean chicken infectious doses and lack of seroconversion in survivors indicated the viruses were poorly chicken adapted. Pathobiological features were consistent with HPAI virus infection, although the delayed appearance of lesions, longer mean death times, and reduced replication in endothelial cells differed from features of most other Eurasian H5N1 HPAI viruses. Although these initial U.S. H5 HPAI viruses had reduced adaptation and transmissibility in chickens, multi-generational passage in poultry could generate poultry adapted viruses with higher infectivity and transmissibility.

Copyright © 2016. Published by Elsevier Inc.

KEYWORDS: Avian influenza; Clade; Highly pathogenic avian influenza; Infectivity; Pathobiology; Poultry; Transmission; Wild waterfowl

PMID: 27110710 [PubMed – as supplied by publisher]

Keywords: Research; Abstracts; H5N2; H5N8; Reassortant Strains; Avian Influenza; Poultry; USA.


#Dengue #Virus #Antibodies Enhance #Zika #Virus #Infection (BioRxIV, abstract)

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

New Results

Dengue Virus Antibodies Enhance Zika Virus Infection

Lauren M Paul, Eric R Carlin, Meagan M Jenkins, Amanda L Tan, Carolyn M Barcellona, Cindo O Nicholson, Lydie Trautmann, Scott F Michael, Sharon Isern

doi: http://dx.doi.org/10.1101/050112




For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases endemic in the same regions. Recent reports of severe disease associated with ZIKV, including Guillain-Barre syndrome and severe fetal abnormalities, have greatly heightened awareness. Given its recent history of rapid spread in immune naive populations, it is anticipated that ZIKV will continue to spread in the Americas and globally in regions where competent Aedes mosquito vectors are found. Globally, dengue virus (DENV) is the most common mosquito-transmitted human flavivirus and is both well-established and the source of outbreaks in areas of recent ZIKV introduction. DENV and ZIKV are closely related, resulting in substantial antigenic overlap. Through a mechanism known as antibody-dependent enhancement (ADE), anti-DENV antibodies can enhance the infectivity of DENV for certain classes of immune cells, causing increased viral production that correlates with severe disease outcomes. Similarly, ZIKV has been shown to undergo ADE in response to antibodies generated by other flaviviruses. However, response to DENV antibodies has not yet been investigated.

Methodology / Principal Findings

We tested the neutralizing and enhancing potential of well-characterized broadly neutralizing human anti-DENV monoclonal antibodies (HMAbs) and human DENV immune sera against ZIKV using neutralization and ADE assays. We show that anti-DENV HMAbs, cross-react, do not neutralize, and greatly enhance ZIKV infection in vitro. DENV immune sera had varying degrees of neutralization against ZIKV and similarly enhanced ZIKV infection.

Conclusions / Significance

Our results suggest that pre-existing DENV immunity will enhance ZIKV infection in vivo and may increase disease severity. A clear understanding of the interplay between ZIKV and DENV will be critical in informing public health responses in regions where these viruses co-circulate and will be particularly valuable for ZIKV and DENV vaccine design and implementation strategies.

Copyright: The copyright holder for this preprint is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.

Keywords: Research; Abstracts; Zika Virus; Dengue Fever; Antibody-Dependent Enhancement.


#Zika #Virus #Outbreak in #Haiti in 2014: #Molecular and #Clinical #Data (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]


Zika Virus Outbreak in Haiti in 2014: Molecular and Clinical Data

John Lednicky, Valery Madsen Beau De Rochars, Maha El Badry, Julia Loeb, Taina Telisma, Sonese Chavannes, Gina Anilis, Eleonora Cella, Massimo Ciccozzi, Mohammed Rashid, Bernard Okech, Marco Salemi, J. Glenn Morris Jr.

Published: April 25, 2016 / http://dx.doi.org/10.1371/journal.pntd.0004687




Zika virus (ZIKV), first isolated in Uganda in 1947, is currently spreading rapidly through South America and the Caribbean. In Brazil, infection has been linked with microcephaly and other serious complications, leading to declaration of a public health emergency of international concern; however, there currently are only limited data on the virus (and its possible sources and manifestations) in the Caribbean.


From May, 2014-February, 2015, in conjunction with studies of chikungunya (CHIKV) and dengue (DENV) virus infections, blood samples were collected from children in the Gressier/Leogane region of Haiti who presented to a school clinic with undifferentiated febrile illness. Samples were initially screened by RT-PCR for CHIKV and DENV, with samples negative in these assays further screened by viral culture.


Of 177 samples screened, three were positive for ZIKV, confirmed by viral sequencing; DENV-1 was also identified in culture from one of the three positive case patients. Patients were from two different schools and 3 different towns, with all three cases occurring within a single week, consistent with the occurrence of an outbreak in the region. Phylogenetic analysis of known full genome viral sequences demonstrated a close relationship with ZIKV from Brazil; additional analysis of the NS5 gene, for which more sequences are currently available, showed the Haitian strains clustering within a monophyletic clade distinct from Brazilian, Puerto Rican and Guatemalan sequences, with all part of a larger clade including isolates from Easter Island. Phylogeography also clarified that at least three major African sub-lineages exist, and confirmed that the South American epidemic is most likely to have originated from an initial ZIKV introduction from French Polynesia into Easter Island, and then to the remainder of the Americas.


ZIKV epidemics in South America, as well as in Africa, show complex dissemination patterns. The virus appears to have been circulating in Haiti prior to the first reported cases in Brazil. Factors contributing to transmission and the possible linkage of this early Haitian outbreak with microcephaly remain to be determined.

Author Summary

Zika virus is currently spreading rapidly through the Americas, including the Caribbean, where it has emerged as a major public health problem due to the linkage with birth defects, including microcephaly. We report the isolation of Zika virus from 3 children in rural Haiti in December, 2014, as part of a study of acute undifferentiated febrile illness that was being conducted by our research group; from one of these children, we also isolated dengue virus serotype 1. On analysis of nucleotide sequence data from these and Zika strains from other locales, the South American/Haitian sequences cluster within the Asian clade and clearly branch out from a sequence circulating in Easter Island, which originated, in turn, from French Polynesia. On further analysis of one specific gene sequence for which more data were available, there appeared to be slight separation of Haitian strains and the strains from Brazil, Suriname, Puerto Rico and Guatemala, with molecular clock analysis suggesting that Zika virus was present in Haiti as early as mid-2013. These findings raise questions about the origin of Zika virus in the Caribbean, and subsequent patterns of circulation of the virus within the Americas.


Citation: Lednicky J, Beau De Rochars VM, El Badry M, Loeb J, Telisma T, Chavannes S, et al. (2016) Zika Virus Outbreak in Haiti in 2014: Molecular and Clinical Data. PLoS Negl Trop Dis 10(4): e0004687. doi:10.1371/journal.pntd.0004687

Editor: Richard Reithinger, RTI International, UNITED STATES

Received: March 2, 2016; Accepted: April 13, 2016; Published: April 25, 2016

Copyright: © 2016 Lednicky 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: Sequence data is available in GenBank (accession number KU509998).

Funding: The authors received no funding outside of the University of Florida for the work described. Funding was from an internal University of Florida pilot grant fund. Funders 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: Research; Abstracts; Zika Virus; Haiti.


#Production of Potent Fully #Human #Polyclonal #Antibodies against #Ebola #Zaire Virus in Transchromosomal #Cattle (Sci Rep., abstract)

[Source: Scientific Reports, full page: (LINK). Abstract, edited.]

Article | Open

Production of Potent Fully Human Polyclonal Antibodies against Ebola Zaire Virus in Transchromosomal Cattle

John M. Dye, Hua Wu, Jay W. Hooper, Surender Khurana, Ana I. Kuehne, Elizabeth M. Coyle, Ramon A. Ortiz, Sandra Fuentes, Andrew S. Herbert, Hana Golding, Russell A. Bakken, Jennifer M. Brannan, Steve A. Kwilas, Eddie J. Sullivan, Thomas C. Luke, Gale Smith, Gregory Glenn, Wenfang Li, Ling Ye, Chinglai Yang, Richard W. Compans, Ralph A. Tripp & Jin-an Jiao

Scientific Reports 6, Article number: 24897 (2016) / doi:10.1038/srep24897

Received: 01 October 2015 – Accepted: 07 April 2016 – Published online: 25 April 2016



Polyclonal antibodies, derived from humans or hyperimmunized animals, have been used prophylactically or therapeutically as countermeasures for a variety of infectious diseases. SAB Biotherapeutics has successfully developed a transchromosomic (Tc) bovine platform technology that can produce fully human immunoglobulins rapidly, and in substantial quantities, against a variety of disease targets. In this study, two Tc bovines expressing high levels of fully human IgG were hyperimmunized with a recombinant glycoprotein (GP) vaccine consisting of the 2014 Ebola virus (EBOV) Makona isolate. Serum collected from these hyperimmunized Tc bovines contained high titers of human IgG against EBOV GP as determined by GP specific ELISA, surface plasmon resonance (SPR), and virus neutralization assays. Fully human polyclonal antibodies against EBOV were purified and evaluated in a mouse challenge model using mouse adapted Ebola virus (maEBOV). Intraperitoneal administration of the purified anti-EBOV IgG (100 mg/kg) to BALB/c mice one day after lethal challenge with maEBOV resulted in 90% protection; whereas 100% of the control animals succumbed. The results show that hyperimmunization of Tc bovines with EBOV GP can elicit protective and potent neutralizing fully human IgG antibodies rapidly and in commercially viable quantities.

Keywords: Research; Abstracts; Ebola; Ebola-Makona; Serotherapy.


The #Epidemiology and #Transmissibility of #Zika #Virus in Girardot and San Andres Island, #Colombia (BioRxIV, abstract)

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

New Results

The Epidemiology and Transmissibility of Zika Virus in Girardot and San Andres Island, Colombia

Diana Patricia Rojas, Natalie E. Dean, Yang Yang, Eben Kenah, Juliana Quintero, Simon Tomasi, Erika L. Ramirez, Yendy Kelly, Carolina Castro, Gabriel Carrasquilla, M. Elizabeth Halloran, Ira M. Longini

doi: http://dx.doi.org/10.1101/049957




Zika virus (ZIKV) is an arbovirus in the same genus as dengue virus and yellow fever virus. ZIKV transmission was first detected in Colombia in September 2015. The virus has spread rapidly across the country in areas infested with the vector Aedes aegypti. As of March 2016, Colombia has reported over 50,000 cases of Zika virus disease (ZVD).


We analyzed surveillance data of ZVD cases reported to the local health authorities of San Andres, Colombia, and Girardot, Colombia, between September 2015 and January 2016. Standardized case definitions used in both areas were determined by the Ministry of Health and Colombian National Institute of Health at the beginning of the ZIKV epidemic. ZVD was laboratory- confirmed by a finding of Zika virus RNA in the serum of acute cases. We report epidemiological summaries of the two outbreaks. We also use daily incidence data to estimate the basic reproductive number R0 in each population.


We identified 928 and 1,936 laboratory or clinically confirmed cases in San Andres and Girardot, respectively. The overall attack rate for reported ZVD detected by healthcare local surveillance was 12.13 cases per 1,000 residents of San Andres and 18.43 cases per 1,000 residents of Girardot. Attack rates were significantly higher in females in both municipalities. Cases occurred in all age groups but the most affected group was 20 to 49 year olds. The estimated R0 for the Zika outbreak in San Andres was 1.41 (95% CI 1.15 to 1.74), and in Girardot was 4.61 (95% CI 4.11 to 5.16).


Transmission of ZIKV is ongoing and spreading throughout the Americas rapidly. The observed rapid spread is supported by the relatively high basic reproductive numbers calculated from these two outbreaks in Colombia.

Copyright: The copyright holder for this preprint is the author/funder. It is made available under a CC-BY-ND 4.0 International license.

Keywords: Research; Abstracts; Zika Virus; Colombia.


#Reconstruction of #disease #transmission #rates: applications to #measles, #dengue, and #influenza (J Theor Biol., abstract)

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

J Theor Biol. 2016 Apr 19. pii: S0022-5193(16)30045-5. doi: 10.1016/j.jtbi.2016.04.017. [Epub ahead of print]

Reconstruction of disease transmission rates: applications to measles, dengue, and influenza.

Lange A1.

Author information: 1Department of Mathematics and Statistics, McMaster University, Canada; Institute of Thermodynamics and Thermal Process Engineering, University of Stuttgart, Germany Zuse Institute Berlin, Germany. Electronic address: lange@zib.de.



Transmission rates are key in understanding the spread of infectious diseases. Using the framework of compartmental models, we introduce a simple method to reconstruct time series of transmission rates directly from incidence or disease-related mortality data. The reconstruction exploits differential equations, which model the time evolution of infective stages and strains. Being sensitive to initial values, the method produces asymptotically correct solutions. The computations are fast, with time complexity being quadratic. We apply the reconstruction to data of measles (England and Wales, 1948-67), dengue (Thailand, 1982-99), and influenza (U.S., 1910-27). The Measles example offers comparison with earlier work. Here we re-investigate reporting corrections, include and exclude demographic information. The dengue example deals with the failure of vector-control measures in reducing dengue hemorrhagic fever (DHF) in Thailand. Two competing mechanisms have been held responsible: strain interaction and demographic transitions. Our reconstruction reveals that both explanations are possible, showing that the increase in DHF cases is consistent with decreasing transmission rates resulting from reduced vector counts. The flu example focuses on the 1918/19 pandemic, examining the transmission rate evolution for an invading strain. Our analysis indicates that the pandemic strain could have circulated in the population for many months before the pandemic was initiated by an event of highly increased transmission.

Copyright © 2016. Published by Elsevier Ltd.

KEYWORDS: Differential equation models; Disease transmission; Infectious disease modeling

PMID: 27105674 [PubMed – as supplied by publisher]

Keywords: Research; Abstracts; Spanish Flu; Measles; Dengue.


#Cannabis, #Psychosis, and #Mortality: A Cohort Study of 50,373 #Swedish Men (Am J Psychiatry, abstract)

[Source: The American Journal of Psychiatry, full page: (LINK). Abstract, edited.]


Cannabis, Psychosis, and Mortality: A Cohort Study of 50,373 Swedish Men

Edison Manrique-Garcia, M.D., Ph.D., Antonio Ponce de Leon, Ph.D., Christina Dalman, M.D., Ph.D., Sven Andréasson, M.D., Ph.D., Peter Allebeck, M.D., Ph.D.

Received: May 19, 2014 / Accepted: March 07, 2016 / Published online: April 22, 2016 / http://dx.doi.org/10.1176/appi.ajp.2016.14050637




The authors assessed 1) the overall risk of death among cannabis users compared with nonusers and the extent to which psychosis affects excess mortality; 2) mortality among persons with psychotic disorders and the extent to which cannabis use affects excess mortality; and 3) the interaction effect of cannabis use and diagnosis of psychotic disorders on mortality.


This was a longitudinal study of 50,373 Swedish male military conscripts (ages 18–19) who were followed in the National Cause of Death Register up to around age 60. Cox proportional hazard modeling was used to assess risk of death in relation to baseline cannabis use and diagnosis of psychotic disorders.


Subjects with a baseline history of heavy cannabis use had a significantly higher risk of death (hazard ratio=1.4, 95% CI=1.1, 1.8) than those without such a history. The authors found an excess mortality among subjects with psychotic disorders, but the level did not differ between those with a history of cannabis use (ever users: hazard ratio=3.8, 95% CI=2.8, 5.0; heavy users: hazard ratio=3.8, 95% CI=2.6, 6.2) and those without such a history (hazard ratio=3.7, 95% CI=3.1, 44). No interaction was observed between cannabis use and diagnosis of psychotic disorders with regard to mortality.


The results suggest that individuals with an early history of heavy use of cannabis are at a higher risk of death than those with a history of no use of cannabis. Although the authors adjusted for several confounders at baseline, the results should be interpreted with caution because of a lack of information on confounders in the period after conscription.

Keywords: Research; Abstracts; Psychiatry; Cannabis.


Role of #Berberine in the #Treatment of #MRSA #Infections (Sci Rep., abstract)

[Source: Scientific Reports, full page: (LINK). Abstract, edited.]

Article | Open

Role of Berberine in the Treatment of Methicillin-Resistant Staphylococcus aureus Infections

Ming Chu, Ming-bo Zhang, Yan-chen Liu, Jia-rui Kang, Zheng-yun Chu, Kai-lin Yin, Ling-yu Ding, Ran Ding, Rong-xin Xiao, Yi-nan Yin, Xiao-yan Liu & Yue-dan Wang

Scientific Reports 6, Article number: 24748 (2016) / doi:10.1038/srep24748

Received: 18 December 2015 – Accepted: 04 April 2016 – Published online: 22 April 2016



Berberine is an isoquinoline alkaloid widely used in the treatment of microbial infections. Recent studies have shown that berberine can enhance the inhibitory efficacy of antibiotics against clinical multi-drug resistant isolates of methicillin-resistant Staphylococcus aureus (MRSA). However, the underlying mechanisms are poorly understood. Here, we demonstrated that sub-minimum inhibitory concentrations (MICs) of berberine exhibited no bactericidal activity against MRSA, but affected MRSA biofilm development in a dose dependent manner within the concentration ranging from 1 to 64 μg/mL. Further study indicated that berberine inhibited MRSA amyloid fibrils formation, which consist of phenol-soluble modulins (PSMs). Molecular dynamics simulation revealed that berberine could bind with the phenyl ring of Phe19 in PSMα2 through hydrophobic interaction. Collectively, berberine can inhibit MRSA biofilm formation via affecting PSMs’ aggregation into amyloid fibrils, and thereby enhance bactericidal activity of antibiotics. These findings will provide new insights into the multiple pharmacological properties of berberine in the treatment of microbial-generated amyloid involved diseases.

Keywords: Research; Abstracts; Antibiotics; Drugs Resistance; Staphylococcus Aureus; Barberine.