Virulome and pathogenicity of carbapenem- and polymyxin-resistant priority pathogens

• Grant number: 19/15578-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2019
• Effective date (End): January 31, 2023
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Nilton Erbet Lincopan Huenuman
• Grantee: Fernanda Ribeiro dos Santos Esposito
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The convergence of hypervirulence and resistance to carbapenems and polymyxins in pathogens considered as priority by the World Health Organization (WHO), such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli has begun to be reported worldwide, posing a major threat to the prognosis and control of healthcare-associated infections (IRAS) and infections prevalent in Veterinary Medicine, which is a unified health problem. In Brazil, the identification of clonal lineages of carbapenem-resistant pathogens (KPC-2, SPM-1, NDM-1 or VIM-2 carbapenemase producers) and/or polymyxins (due to mutations or MCR-1 production) has acquired an endemic character. Regarding this, although resistance phenomenon has been shown to contribute to the rapid adaptation of these pathogens in different ecosystems and hosts, the role of virulome and the convergence of hypervirulence and resistance remain underexplored. Thus, through a genomic approach and in vitro (cell culture) and in vivo assays (using Galleria mellonella invertebrate model), the bacterial fitness and pathogenicity of lineages of K. pneumoniae, E. coli, and P. aeruginosa resistant to carbapenems and/or polymyxins will be evaluated by the following features; presence and absence of virulence and resistance genes, clonal diversity (ST/MLST) and growth type [planktonic/sessile (biofilm)]; aiming to identify the convergence phenomenon of hypervirulence and resistance, and other aspects that could be contributing to the unfavorable prognosis of the associated infections by these priority pathogens. A priori, it is intended to characterize the entire virulome of endemic strains, and identify biomarkers for diagnostic purposes, management, and prevention of infections considered clinical and epidemiological urgencies, both in human and veterinary Medicine. (AU)

Scientific publications

(9)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ROSALES-REYES, ROBERTO; ESPOSITO, FERNANDA; FONTANA, HERRISON; LEZANA-FERNANDEZ, JOSE LUIS; LASCURAIN, RICARDO; DE LA CRUZ, MIGUEL A.; FUGA, BRUNA; LINCOPAN, NILTON; SANTOS-PRECIADO, JOSE IGNACIO. mergence of GES-19-producing Pseudomonas aeruginosa exoU plus belonging to the global high-risk clone ST235 in cystic fibrosis infectio. DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, v. 101, n. 1, SEP 2021. (19/15578-4)

ESPOSITO, FERNANDA; CARDOSO, BRENDA; FONTANA, HERRISON; FUGA, BRUNA; CARDENAS-ARIAS, ADRIANA; MOURA, QUEZIA; FUENTES-CASTILLO, DANNY; LINCOPAN, NILTON. Genomic Analysis of Carbapenem-Resistant Pseudomonas aeruginosa Isolated From Urban Rivers Confirms Spread of Clone Sequence Type 277 Carrying Broad Resistome and Virulome Beyond the Hospital. FRONTIERS IN MICROBIOLOGY, v. 12, SEP 3 2021. (20/08224-9, 19/15578-4)

ROSALES-REYES, ROBERTO; ESPOSITO, FERNANDA; FUGA, BRUNA; CERDEIRA, LOUISE; GAYOSSO-VAZQUEZ, CATALINA; LEZANA-FERNANDEZ, JOSE L.; LASCURAIN, RICARDO; VALVANO, MIGUEL A.; LINCOPAN, NILTON; SANTOS-PRECIADO, JOSE I.. Draft Genome Sequence of a Pseudomonas aeruginosa Sequence Type 3351 Strain Exhibiting High-Level Resistance to Polymyxins in a Pediatric Patient with Cystic Fibrosis in Mexico. MICROBIOLOGY RESOURCE ANNOUNCEMENTS, v. 9, n. 2, JAN 2020. (19/15578-4)

MOHSIN, MASHKOOR; AZAM, MARIYA; RAHMAN, SAJJAD UR; ESPOSITO, FERNANDA; SELLERA, FABIO P.; MONTE, DANIEL F.; CERDEIRA, LOUISE; LINCOPAN, NILTON. Genomic background of a colistin-resistant and highly virulent MCR-1-positive Escherichia coli ST6395 from a broiler chicken in Pakistan. PATHOGENS AND DISEASE, v. 77, n. 7, OCT 2019. (16/08593-9, 19/15578-4)

DOS ANJOS, CAROLINA; SABINO, CAETANO P.; SELLERA, FABIO P.; ESPOSITO, FERNANDA; POGLIANI, FABIO C.; LINCOPAN, NILTON. Hypervirulent and hypermucoviscous strains of Klebsiella pneumoniae challenged by antimicrobial strategies using visible light. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, v. 56, n. 1, JUL 2020. (19/10851-4, 16/25095-2, 19/15578-4, 17/22406-0)

CARDOSO, BRENDA; FONTANA, HERRISON; ESPOSITO, FERNANDA; CERDEIRA, LOUISE; SANTOS, SILVIA R.; YOSHIOKA, CRISTINA R. M.; DA SILVEIRA, ISA R.; CASSETTARI, VALERIA; LINCOPAN, NILTON. Genomic insights of international clones of Haemophilus influenzae causing invasive infections in vaccinated and unvaccinated infants. Microbial Pathogenesis, v. 150, JAN 2021. (19/15578-4)

FUENTES-CASTILLO, DANNY; SELLERA, FABIO P.; GOLDBERG, DAPHNE W.; FONTANA, HERRISON; ESPOSITO, FERNANDA; CARDOSO, BRENDA; IKEDA, JOANA; KYLLAR, ANNELIESE; CATAO-DIAS, JOSE L.; LINCOPAN, NILTON. Colistin-resistant Enterobacter kobei carrying mcr-9.1 and bla(CTX-M-15) infecting a critically endangered franciscana dolphin (Pontoporia blainvillei), Brazil. TRANSBOUNDARY AND EMERGING DISEASES, v. 68, n. 6, p. 3048-3054, NOV 2021. (19/15578-4)

DE MELLO SANTOS, ANA CAROLINA; FUGA, BRUNA; ESPOSITO, FERNANDA; CARDOSO, BRENDA; SANTOS, FERNANDA FERNANDES; VALIATTI, TIAGO BARCELOS; SANTOS-NETO, JOSE FRANCISCO; GALES, ANA CRISTINA; LINCOPAN, NILTON; SILVA, ROSA MARIA; et al. Unveiling the Virulent Genotype and Unusual Biochemical Behavior of Escherichia coli ST59. Applied and Environmental Microbiology, v. 87, n. 16, AUG 2021. (19/15578-4, 09/00402-6, 18/17353-7)

EWBANK, ANA CAROLINA; FUENTES-CASTILLO, DANNY; SACRISTAN, CARLOS; CARDOSO, BRENDA; ESPOSITO, FERNANDA; FUGA, BRUNA; DE MACEDO, EDUARDO CAVALCANTE; LINCOPAN, NILTON; CATAO-DIAS, JOSE LUIZ. Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli survey in wild seabirds at a pristine atoll in the southern Atlantic Ocean, Brazil: First report of the O25b-ST131 clone harboring bla(CTX-M-8). Science of The Total Environment, v. 806, n. 2, FEB 1 2022. (19/15578-4, 18/25069-7)