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INFECTION BY A MULTIDRUG-RESISTANT CORYNEBACTERIUM DIPHTHERIAE STRAIN: PREDICTION OF VIRULENCE FACTORS, CRISPR-CAS SYSTEM ANALYSIS, AND STRUCTURAL IMPLICATIONS OF MUTATIONS CONFERRING RIFAMPIN RESISTANCE
Non-toxigenic
Virulence factors
Resistance genes
CRISPR-Cas system
Rifampin resistance
Author
Araújo, Max Roberto Batista de
Prates, Fernanda Diniz
Ramos, Juliana Nunes
Sousa, Eduarda Guimarães
Bokermann, Sérgio
Sacchi, Cláudio Tavares
Guaraldi, Ana Luiza de Mattos
Campos, Karoline Rodrigues
Sousa, Mireille Ângela Bernardes
Vieira, Verônica Viana
Santos, Marlon Benedito Nascimento
Camargo, Carlos Henrique
Sant'Anna, Lincoln de Oliveira
Sant'Anna, Louisy Sanches dos Santos
Azevedo, Vasco Ariston de Carvalho
Prates, Fernanda Diniz
Ramos, Juliana Nunes
Sousa, Eduarda Guimarães
Bokermann, Sérgio
Sacchi, Cláudio Tavares
Guaraldi, Ana Luiza de Mattos
Campos, Karoline Rodrigues
Sousa, Mireille Ângela Bernardes
Vieira, Verônica Viana
Santos, Marlon Benedito Nascimento
Camargo, Carlos Henrique
Sant'Anna, Lincoln de Oliveira
Sant'Anna, Louisy Sanches dos Santos
Azevedo, Vasco Ariston de Carvalho
Affilliation
Hermes Pardini Institute. Microbiology. Operational Technical Nucleus. Vespasiano, MG, Brasil / Federal University of Minas Gerais. Department of Genetics, Ecology and Evolution. Belo Horizonte, MG, Brasil.
Hermes Pardini Institute. Microbiology. Operational Technical Nucleus. Vespasiano, MG, Brasil / Federal University of Minas Gerais. Department of Genetics, Ecology and Evolution. Belo Horizonte, MG, Brasil.
Universidade do Estado do Rio de Janeiro. Centro Biomédico. Faculdade de Ciências Médicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Difteria e Corinebactérias de Importância Clínica. Rio de Janeiro, RJ, Brasil.
Federal University of Minas Gerais. Department of Genetics, Ecology and Evolution. Belo Horizonte, MG, Brasil.
Secretary of Health of the State of São Paulo. Adolfo Lutz Institute. Center of Bacteriology. São Paulo, SP, Brasil.
Secretary of Health of the State of São Paulo. Adolfo Lutz Institute. Strategic Laboratory. São Paulo, SP, Brasil.
Universidade do Estado do Rio de Janeiro. Centro Biomédico. Faculdade de Ciências Médicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Difteria e Corinebactérias de Importância Clínica. Rio de Janeiro, RJ, Brasil.
Secretary of Health of the State of São Paulo. Adolfo Lutz Institute. Strategic Laboratory. São Paulo, SP, Brasil.
Hermes Pardini Institute. Microbiology. Operational Technical Nucleus. Vespasiano, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.
Secretary of Health of the State of São Paulo. Adolfo Lutz Institute. Strategic Laboratory. São Paulo, SP, Brasil.
Secretary of Health of the State of São Paulo. Adolfo Lutz Institute. Center of Bacteriology. São Paulo, SP, Brasil.
Federal University of Minas Gerais. Department of Genetics, Ecology and Evolution. Belo Horizonte, MG, Brasil.
Federal University of Minas Gerais. Department of Genetics, Ecology and Evolution. Belo Horizonte, MG, Brasil.
Federal University of Minas Gerais. Department of Genetics, Ecology and Evolution. Belo Horizonte, MG, Brasil.
Hermes Pardini Institute. Microbiology. Operational Technical Nucleus. Vespasiano, MG, Brasil / Federal University of Minas Gerais. Department of Genetics, Ecology and Evolution. Belo Horizonte, MG, Brasil.
Universidade do Estado do Rio de Janeiro. Centro Biomédico. Faculdade de Ciências Médicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Difteria e Corinebactérias de Importância Clínica. Rio de Janeiro, RJ, Brasil.
Federal University of Minas Gerais. Department of Genetics, Ecology and Evolution. Belo Horizonte, MG, Brasil.
Secretary of Health of the State of São Paulo. Adolfo Lutz Institute. Center of Bacteriology. São Paulo, SP, Brasil.
Secretary of Health of the State of São Paulo. Adolfo Lutz Institute. Strategic Laboratory. São Paulo, SP, Brasil.
Universidade do Estado do Rio de Janeiro. Centro Biomédico. Faculdade de Ciências Médicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Difteria e Corinebactérias de Importância Clínica. Rio de Janeiro, RJ, Brasil.
Secretary of Health of the State of São Paulo. Adolfo Lutz Institute. Strategic Laboratory. São Paulo, SP, Brasil.
Hermes Pardini Institute. Microbiology. Operational Technical Nucleus. Vespasiano, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.
Secretary of Health of the State of São Paulo. Adolfo Lutz Institute. Strategic Laboratory. São Paulo, SP, Brasil.
Secretary of Health of the State of São Paulo. Adolfo Lutz Institute. Center of Bacteriology. São Paulo, SP, Brasil.
Federal University of Minas Gerais. Department of Genetics, Ecology and Evolution. Belo Horizonte, MG, Brasil.
Federal University of Minas Gerais. Department of Genetics, Ecology and Evolution. Belo Horizonte, MG, Brasil.
Federal University of Minas Gerais. Department of Genetics, Ecology and Evolution. Belo Horizonte, MG, Brasil.
Abstract
Cases of diphtheria, even in immunized individuals, are still reported in several parts of the world, including in Brazil. New outbreaks occur in Europe and other continents. In this context, studies on Corynebacterium diphtheriae infections are highly relevant, both for a better understanding of the pathogenesis of the disease and for controlling the circulation of clones and antimicrobial resistance genes. Here we present a case of cutaneous infection by multidrug-resistant Corynebacterium diphtheriae and provide its whole-genome sequencing. Genomic analysis revealed resistance genes, including tet(W), sul1, cmx, rpoB2, rbpA and mutation in rpoB. We performed phylogenetic analyzes and used the BRIG to compare the predicted resistance genes with those found in genomes from other significant isolates, including those associated with some outbreaks. Virulence factors such as spaD, srtBC, spaH, srtDE, surface-anchored pilus proteins (sapD), nonfimbrial adhesins (DIP0733, DIP1281, and DIP1621), embC and mptC (putatively involved in CdiLAM), sigA, dtxR and MdbA (putatively involved) in post-translational modification, were detected. We identified the CRISPR-Cas system in our isolate, which was classified as Type II-U based on the database and contains 15 spacers. This system functions as an adaptive immune mechanism. The strain was attributed to a new sequence type ST-928, and phylogenetic analysis confirmed that it was related to ST-634 of C. diphtheriae strains isolated in French Guiana and Brazil. In addition, since infections are not always reported, studies with the sequence data might be a way to complement and inform C. diphtheriae surveillance.
Keywords
Corynebacterium diphtheriae complexNon-toxigenic
Virulence factors
Resistance genes
CRISPR-Cas system
Rifampin resistance
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