#Enzootic #patterns of #MERS #coronavirus in imported #African and local #Arabian dromedary #camels: a prospective genomic study (Lancet Planet Health, abstract)

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

Lancet Planet Health. 2019 Dec 11. pii: S2542-5196(19)30243-8. doi: 10.1016/S2542-5196(19)30243-8. [Epub ahead of print]

Enzootic patterns of Middle East respiratory syndrome coronavirus in imported African and local Arabian dromedary camels: a prospective genomic study.

El-Kafrawy SA1, Corman VM2, Tolah AM3, Al Masaudi SB4, Hassan AM5, Müller MA6, Bleicker T7, Harakeh SM1, Alzahrani AA8, Alsaaidi GA8, Alagili AN9, Hashem AM10, Zumla A11, Drosten C12, Azhar EI13.

Author information: 1 Special Infectious Agent Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia. 2 Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Germany; Berlin Institute of Health, Institute of Virology, Berlin, Germany; German Centre for Infection Research, associated partner Charité, Berlin, Germany. 3 Special Infectious Agent Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Biological Science, Division of Microbiology, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. 4 Department of Biological Science, Division of Microbiology, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. 5 Special Infectious Agent Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. 6 Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Germany; Berlin Institute of Health, Institute of Virology, Berlin, Germany; German Centre for Infection Research, associated partner Charité, Berlin, Germany; Martsinovsky Institute of Medical Parasitology, Tropical and Vector Borne Diseases, Sechenov University, Moscow, Russia. 7 Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Germany; Berlin Institute of Health, Institute of Virology, Berlin, Germany. 8 Directorate of Agriculture, Ministry of Environment Water and Agriculture, Makkah Region, Saudi Arabia. 9 Mammals Research Chair, Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia. 10 Special Infectious Agent Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. 11 Department of Infection, Division of Infection and Immunity, Centre for Clinical Microbiology, University College London, London, UK; NIHR Biomedical Research Centre, University College London Hospitals, London, UK. 12 Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Germany; Berlin Institute of Health, Institute of Virology, Berlin, Germany; German Centre for Infection Research, associated partner Charité, Berlin, Germany. Electronic address: christian.drosten@charite.de. 13 Special Infectious Agent Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: eazhar@kau.edu.sa.

 

Abstract

BACKGROUND:

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen endemic to the Arabian Peninsula. Dromedary camels are a likely source of infection and the virus probably originated in Africa. We studied the genetic diversity, geographical structure, infection prevalence, and age-associated prevalence among camels at the largest entry port of camels from Africa into the Arabian Peninsula.

METHODS:

In this prospective genomic study, we took nasal samples from camels imported from Sudan and Djibouti into the Port of Jeddah in Jeddah, Saudi Arabia, over an almost 2-year period and local Arabian camels over 2 months in the year after surveillance of the port. We determined the prevalence of MERS-CoV infection, age-associated patterns of infection, and undertook phylogeographical and migration analyses to determine intercountry virus transmission after local lineage establishment. We compared all virological characteristics between the local and imported cohorts. We compared major gene deletions between African and Arabian strains of the virus. Reproductive numbers were inferred with Bayesian birth death skyline analyses.

FINDINGS:

Between Aug 10, 2016, and May 3, 2018, we collected samples from 1196 imported camels, of which 868 originated from Sudan and 328 from Djibouti, and between May 1, and June 25, 2018, we collected samples from 472 local camels, of which 189 were from Riyadh and 283 were from Jeddah, Saudi Arabia. Virus prevalence was higher in local camels than in imported camels (224 [47·5%] of 472 vs 157 [13·1%] of 1196; p<0·0001). Infection prevalence peaked among camels older than 1 year and aged up to 2 years in both groups, with 255 (66·9%) of 381 positive cases in this age group. Although the overall geographical distribution of the virus corresponded with the phylogenetic tree topology, some virus exchange was observed between countries corresponding with trade routes in the region. East and west African strains of the virus appear to be geographically separated, with an origin of west African strains in east Africa. African strains of the virus were not re-sampled in Saudi Arabia despite sampling approximately 1 year after importation from Africa. All local Arabian samples contained strains of the virus that belong to a novel recombinant clade (NRC) first detected in 2014 in Saudi Arabia. Reproduction number estimates informed by the sequences suggest sustained endemicity of NRC, with a mean Re of 1·16.

INTERPRETATION:

Despite frequent imports of MERS-CoV with camels from Africa, African lineages of MERS-CoV do not establish themselves in Saudi Arabia. Arabian strains of the virus should be tested for changes in virulence and transmissibility.

FUNDING:

German Ministry of Research and Education, EU Horizon 2020, and Emerging Diseases Clinical Trials Partnership.

Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

PMID: 31843456 DOI: 10.1016/S2542-5196(19)30243-8

Keywords: MERS-CoV; Camels; Africa Region; Saudi Arabia; Recombination.

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#Genetic #diversity of #MERS-CoV spike protein gene in #Saudi Arabia (J Infect Public Health, abstract)

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

J Infect Public Health. 2019 Dec 9. pii: S1876-0341(19)30345-4. doi: 10.1016/j.jiph.2019.11.007. [Epub ahead of print]

Genetic diversity of MERS-CoV spike protein gene in Saudi Arabia.

Sohrab SS1, Azhar EI2.

Author information: 1 Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, 21589, Saudi Arabia. Electronic address: ssohrab@kau.edu.sa. 2 Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.

 

Abstract

BACKGROUND:

Middle East respiratory syndrome coronavirus (MERS-CoV) was primarily detected in 2012 and still causing disease in human and camel. Camel and bats have been identified as a potential source of virus for disease spread to human. Although, significant information related to MERS-CoV disease, spread, infection, epidemiology, clinical features have been published, A little information is available on the sequence diversity of Spike protein gene. The Spike protein gene plays a significant role in virus attachment to host cells. Recently, the information about recombinant MERS-CoV has been published. So, this work was designed to identify the emergence of any another recombinant virus in Jeddah, Saudi Arabia.

METHODS:

In this study samples were collected from both human and camels and the Spike protein gene was amplified and sequenced. The nucleotide and amino acid sequences of MERS-CoV Spike protein gene were used to analyze the recombination, genetic diversity and phylogenetic relationship with selected sequences from Saudi Arabia.

RESULTS:

The nucleotide sequence identity ranged from 65.7% to 99.8% among all the samples collected from human and camels from various locations in the Kingdom. The lowest similarity (65.7%) was observed in samples from Madinah and Dammam. The phylogenetic relationship formed different clusters with multiple isolates from various locations. The sample collected from human in Jeddah hospital formed a closed cluster with human samples collected from Buraydah, while camel sample formed a closed cluster with Hufuf isolates. The phylogenetic tree by using Aminoacid sequences formed closed cluster with Dammam, Makkah and Duba isolates. The amino acid sequences variations were observed in 28/35 samples and two unique amino acid sequences variations were observed in all samples analyzed while total 19 nucleotides sequences variations were observed in the Spike protein gene. The minor recombination events were identified in eight different sequences at various hotspots in both human and camel samples using recombination detection programme.

CONCLUSION:

The generated information from this study is very valuable and it will be used to design and develop therapeutic compounds and vaccine to control the MERS-CoV disease spread in not only in the Kingdom but also globally.

Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

KEYWORDS: Camel; Genetic diversity; Human; MERS-CoV; Saudi Arabia

PMID: 31831395 DOI: 10.1016/j.jiph.2019.11.007

Keywords: MERS-CoV; Human; Camels; Recombination; Saudi Arabia.

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#Serological evidence of #MERS-CoV and #HKU8-related #Coronavirus #coinfection in #Kenyan #camels (Emerg Microbes Infect., abstract)

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

Emerg Microbes Infect. 2019;8(1):1528-1534. doi: 10.1080/22221751.2019.1679610.

Serological evidence of MERS-CoV and HKU8-related CoV co-infection in Kenyan camels.

Zhang W1, Zheng XS1,2, Agwanda B3, Ommeh S4, Zhao K1,2, Lichoti J5, Wang N1, Chen J1,2, Li B1, Yang XL1, Mani S6, Ngeiywa KJ5,7, Zhu Y1, Hu B1, Onyuok SO1, Yan B1, Anderson DE6, Wang LF6, Zhou P1, Shi ZL1.

Author information: 1 CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences , Wuhan , People’s Republic of China. 2 University of Chinese Academy of Sciences , Beijing , People’s Republic of China. 3 Department of Zoology, National Museums of Kenya , Nairobi , Kenya. 4 Institute for Biotechnology Research, Jomo Kenyatta University of Agriculture and Technology , Nairobi , Kenya. 5 Directorate of Veterinary Services, State Department of Livestock, Ministry of Agriculture , Livestock and Fisheries , Kenya. 6 Programme in Emerging Infectious Diseases Duke-NUS Medical School , Singapore , Singapore. 7 Kenya Camel Association , Nairobi , Kenya.

 

Abstract

Dromedary camels are important reservoir hosts of various coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV) that cause human infections. CoV genomes regularly undergo recombination during infection as observed in bat SARS-related CoVs. Here we report for the first time that only a small proportion of MERS-CoV receptor-binding domain positive (RBD) of spike protein positive camel sera in Kenya were also seropositive to MERS-CoV nucleocapsid (NP). In contrast, many of them contain antibodies against bat HKU8-related (HKU8r)-CoVs. Among 584 camel samples that were positive against MERS-CoV RBD, we found only 0.48 (8.22%) samples were also positive for NP. Furthermore, we found bat HKU8r-CoV NP antibody in 73 (12.5%) of the MERS-CoV RBD positive and NP negative samples, yet found only 3 (0.43%) of the HKU8r-CoV S1 antibody in the same samples. These findings may indicate co-infection with MERS-CoV and a HKU8r-CoV in camels. It may also raise the possibility of the circulation of a recombinant coronavirus virus with the spike of MERS-CoV and the NP of a HKU8r-CoV in Kenya. We failed to find molecular evidence of an HKU8r-CoV or a putative recombinant virus. Our findings should alert other investigators to look for molecular evidence of HKU8r-CoV or recombinants.

KEYWORDS: HKU8; MERS; bat; camel; coronavirus

PMID: 31645223 DOI: 10.1080/22221751.2019.1679610

Keywords: MERS-CoV; Coronavirus; Bats; Camels; Recombination; Kenya.

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#Genetic and #phenotypic characterization of recently discovered #EV-D111 (PLoS Negl Trop Dis., abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Genetic and phenotypic characterization of recently discovered enterovirus D type 111

Serge Alain Sadeuh-Mba , Marie-Line Joffret , Arthur Mazitchi, Marie-Claire Endegue-Zanga, Richard Njouom, Francis Delpeyroux, Ionela Gouandjika-Vasilache , Maël Bessaud

Published: October 17, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007797 / This is an uncorrected proof.

 

Abstract

Members of the species Enterovirus D (EV-D) remain poorly studied. The two first EV-D types (EV-D68 and EV-D70) have regularly caused outbreaks in humans since their discovery five decades ago but have been neglected until the recent occurrence of severe respiratory diseases due to EV-D68. The three other known EV-D types (EV-D94, EV-D111 and EV-D120) were discovered in the 2000s-2010s in Africa and have never been observed elsewhere. One strain of EV-D111 and all known EV-D120s were detected in stool samples of wild non-human primates, suggesting that these viruses could be zoonotic viruses. To date, EV-D111s are only known through partial genetic sequences of the few strains that have been identified so far. In an attempt to bring new pieces to the puzzle, we genetically characterized four EV-D111 strains (among the seven that have been reported until now). We observed that the EV-D111 strains from human samples and the unique simian EV-D111 strain were not phylogenetically distinct, thus suggesting a recent zoonotic transmission. We also discovered evidences of probable intertypic genetic recombination events between EV-D111s and EV-D94s. As recombination can only happen in co-infected cells, this suggests that EV-D94s and EV-D111s share common replication sites in the infected hosts. These sites could be located in the gut since the phenotypic analysis we performed showed that, contrary to EV-D68s and like EV-D94s, EV-D111s are resistant to acid pHs. We also found that EV-D111s induce strong cytopathic effects on L20B cells, a cell line routinely used to specifically detect polioviruses. An active circulation of EV-D111s among humans could then induce a high number of false-positive detection of polioviruses, which could be particularly problematic in Central Africa, where EV-D111 circulates and which is a key region for poliovirus eradication.

 

Author summary

Many examples of emergence of viruses that trigger severe diseases in humans are known. Emergence can be due to the sudden increase of the pathogenic power of a virus that had silently circulated into human populations for a long period; it can also be due to the cross-species transmission of a virus from its animal host to humans. The recent outbreaks of severe respiratory diseases due to enteroviruses D68 (EV-D68) brought to the light to potency of members of the species Enterovirus D (EV-D) to emerge as severe human pathogens.

By many aspects, EV-Ds are still mysterious: their natural history and epidemiology are poorly studied and even their main hosts remain unknown. For decades, EV-Ds were believed to infect mainly humans but recent data about EV-Ds identified in sub-Saharan Africa support their zoonotic origin. In an attempt to increase our knowledge about EV-Ds, we undertook genetic and phenotypic characterization of four EV-D111 isolates, a virus type that was recently uncovered in humans and in non-human primates in Central Africa. Our results show that EV-D111s are probably enteric viruses and evolve by exchanging genetic sequences with EV-D94.

___

Citation: Sadeuh-Mba SA, Joffret M-L, Mazitchi A, Endegue-Zanga M-C, Njouom R, Delpeyroux F, et al. (2019) Genetic and phenotypic characterization of recently discovered enterovirus D type 111. PLoS Negl Trop Dis 13(10): e0007797. https://doi.org/10.1371/journal.pntd.0007797

Editor: Abdallah M. Samy, Faculty of Science, Ain Shams University (ASU), EGYPT

Received: December 12, 2018; Accepted: September 18, 2019; Published: October 17, 2019

Copyright: © 2019 Sadeuh-Mba 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 sequence data are available at GenBank (accession numbers: MK032892-MK032898).

Funding: We are grateful for the financial support of the Institut Pasteur (PTR-276) and for the financial support of the World Health Organization. This work was supported by the European Virus Archive goes Global project. The 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: Enterovirus; EV-D111; EV-D94; Recombination.

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#Influenza Virus #Polymerase #Mutation Stabilizes a Foreign Gene Inserted into the Virus Genome by Enhancing the Transcription/Replication Efficiency of the Modified Segment (mBio, abstract)

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

Influenza Virus Polymerase Mutation Stabilizes a Foreign Gene Inserted into the Virus Genome by Enhancing the Transcription/Replication Efficiency of the Modified Segment

Yuri Furusawa, Shinya Yamada, Tiago Jose da Silva Lopes, Jayeeta Dutta, Zenab Khan, Divya Kriti, Harm van Bakel, Yoshihiro Kawaoka

J. S. Malik Peiris, Editor

DOI: 10.1128/mBio.01794-19

 

ABSTRACT

We previously attempted to establish a reporter influenza virus by inserting the gene for the Venus fluorescent protein into the NS segment of influenza A/Puerto Rico/8/34 (PR8, H1N1) virus to yield WT-Venus-PR8. Although the inserted Venus gene was deleted during serial passages of WT-Venus-PR8, we discovered that the PB2-E712D mutation stabilizes the Venus gene. Here, we explored the mechanisms by which Venus gene deletion occurs and how the polymerase mutation stabilizes the Venus gene. Deep sequencing analysis revealed that PB2-E712D does not cause an appreciable change in the mutation rate, suggesting that the stability of the Venus gene is not affected by polymerase fidelity. We found by using quantitative real-time PCR that WT-Venus-PR8 induces high-level interferon beta (IFN-β) expression. The induction of IFN-β expression seemed to result from the reduced transcription/replication efficiency of the modified NS segment in WT-Venus-PR8. In contrast, the transcription/replication efficiency of the modified NS segment was enhanced by the PB2-E712D mutation. Loss of the Venus gene in WT-Venus-PR8 appeared to be caused by internal deletions in the NS segment. Moreover, to further our understanding of the Venus stabilization mechanisms, we identified additional amino acid mutations in the virus polymerase complex that stabilize the Venus gene. We found that some of these amino acids are located near the template exit or the product exit of the viral polymerase, suggesting that these amino acids contribute to the stability of the Venus gene by affecting the binding affinity between the polymerase complex and the RNA template and product.

 

IMPORTANCE

The reverse genetics method of influenza virus generation has enabled us to generate recombinant viruses bearing modified viral proteins. Recombinant influenza viruses expressing foreign genes have become useful tools in basic research, and such viruses can be utilized as efficient virus vectors or multivalent vaccines. However, the insertion of a foreign gene into the influenza virus genome often impairs virus replication, and the inserted genes are unstable. Elucidation of the mechanisms of foreign gene stabilization will help us to establish useful recombinant influenza viruses.

Keywords: Influenza A; Recombination.

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#Diversity of dromedary #camel #coronavirus #HKU23 in #African camels revealed multiple #recombination events among closely related #Betacoronaviruses of the subgenus #Embecovirus (J Virol., abstract)

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

Diversity of dromedary camel coronavirus HKU23 in African camels revealed multiple recombination events among closely related Betacoronaviruses of the subgenus Embecovirus.

Ray T. Y. So, Daniel K. W. Chu, Eve Miguel, Ranawaka A. P. M. Perera, Jamiu O. Oladipo, Ouafaa Fassi-Fihri, Gelagay Aylet, Ronald L. W. Ko, Ziqi Zhou, Mo-Sheung Cheng, Sulyman A. Kuranga, François L. Roger, Veronique Chevalier, Richard J. Webby, Patrick C. Y. Woo, Leo L. M. Poon, Malik Peiris

DOI: 10.1128/JVI.01236-19

 

ABSTRACT

Genetic recombination has frequently been observed in coronaviruses. Here, we sequenced multiple complete genomes of dromedary camel coronavirus HKU23 (DcCoV-HKU23) from Nigeria, Morocco and Ethiopia and identified several genomic positions indicative of cross species virus recombination events among other Betacoronaviruses of the subgenus Embecovirus (clade A β-CoVs). Recombinant fragments of a rabbit coronavirus (RbCoV-HKU14) were identified at the hemagglutinin esterase gene position. Homolog fragments of a rodent CoV were also observed at the 8.9 kDa open reading frame 4a at the 3′ end of the spike gene. The patterns of recombination varied geographically across the African region, highlighting a mosaic structure of DcCoV-HKU23 genomes circulating in dromedaries. Our results highlighted active recombination of coronaviruses circulating in dromedaries and is also relevant to the emergence and evolution of other Betacoronaviruses including MERS-coronavirus (MERS-CoV).

 

IMPORTANCE

Genetic recombination is often demonstrated in coronaviruses and can result in host range expansion or alteration in tissue tropism. Here, we showed interspecies recombination events of an endemic dromedary camel coronavirus HKU23 with other clade A Betacoronaviruses. Our results supported the possibility that the zoonotic pathogen, MERS-CoV, which also co-circulates in the same camel species, may have undergone similar recombination events facilitating its emergence or may do so in its future evolution.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Coronavirus; Betacoronavirus; Embecovirus; MERS-CoV; Camels; Africa Region; Recombination.

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#Pandemic #fluoroquinolone #resistant #Escherichia coli clone #ST1193 emerged via simultaneous homologous #recombinations in 11 gene loci (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.]

Pandemic fluoroquinolone resistant Escherichia coli clone ST1193 emerged via simultaneous homologous recombinations in 11 gene loci

Veronika Tchesnokova, Matthew Radey, Sujay Chattopadhyay, Lydia Larson, Jamie Lee Weaver, Dagmara Kisiela, and Evgeni V. Sokurenko

PNAS first published July 1, 2019 / DOI: https://doi.org/10.1073/pnas.1903002116

Edited by W. Ford Doolittle, Dalhousie University, Halifax, NS, Canada, and approved June 5, 2019 (received for review February 19, 2019)

 

Significance

Global growth in antibiotic resistance is a major social and health problem. The most common mechanism of high resistance to fluoroquinolones is the sequential acquisition of 3 mutations in 2 DNA topoisomerases, GyrA and ParC. We show that Escherichia coliST1193 acquired the mutant variants of gyrA and parC not by a conventional stepwise evolution but rather all at once. This was likely a result of a single transfer of about 1 Mb of chromosomal DNA from a phylogenetically distant donor E. coli strain, followed by 11 homologous recombination events involving the transferred DNA. Thus we describe a highly effective mechanism of acquisition of antimicrobial resistance by pathogenic bacteria, which led to the emergence of pandemic E. coli clone ST1193.

 

Abstract

Global growth in antibiotic resistance is a major social problem. A high level of resistance to fluoroquinolones requires the concurrent presence of at least 3 mutations in the target proteins—2 in DNA gyrase (GyrA) and 1 in topoisomerase IV (ParC), which occur in a stepwise manner. In the Escherichia coli chromosome, the gyrA and parC loci are positioned about 1 Mb away from each other. Here we show that the 3 fluoroquinolone resistance mutations are tightly associated genetically in naturally occurring strains. In the latest pandemic uropathogenic and multidrug-resistant E. coli clonal group ST1193, the mutant variants of gyrA and parC were acquired not by a typical gradual, stepwise evolution but all at once. This happened as part of 11 simultaneous homologous recombination events involving 2 phylogenetically distant strains of E. coli, from an uropathogenic clonal complex ST14 and fluoroquinolone-resistant ST10. The gene exchanges swapped regions between 0.5 and 139 Kb in length (183 Kb total) spread along 976 Kb of chromosomal DNA around and between gyrA and parC loci. As a result, all 3 fluoroquinolone resistance mutations in GyrA and ParC have simultaneously appeared in ST1193. Based on molecular clock estimates, this potentially happened as recently as <12 y ago. Thus, naturally occurring homologous recombination events between 2 strains can involve numerous chromosomal gene locations simultaneously, resulting in the transfer of distant but tightly associated genetic mutations and emergence of a both highly pathogenic and antibiotic-resistant strain with a rapid global spread capability.

Escherichia coli ST1193 – urinary tract infections – resistance to fluoroquinolones – homologous recombination – QRDR mutations

 

Footnotes

1 To whom correspondence may be addressed. Email: evs@uw.edu.

Author contributions: V.T. and E.V.S. designed research; V.T., M.R., S.C., L.L., J.L.W., and D.K. performed research; V.T., M.R., S.C., D.K., and E.V.S. analyzed data; and V.T., M.R., S.C., and E.V.S. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1903002116/-/DCSupplemental.

Published under the PNAS license.

Keywords: Antibiotics; Drugs Resistance; Fluoroquinolones; E. Coli; Recombination.

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