Genomic Epidemiology of NDM-producing enterobacteria from Brazil

• Grant number: 20/06157-2
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2020
• End date: October 31, 2022
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Carlos Henrique Camargo
• Grantee: Carlos Henrique Camargo
• Host Institution: Instituto Adolfo Lutz (IAL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Elizabeth Harummyy Takagi ; Marcos Paulo Vieira Cunha ; Monique Ribeiro Tiba Casas

Abstract

Healthcare associate infections (HAIs) caused by multi-resistant microorganisms pose a challenging to clinical practice, as they have a negative impact on associated morbidity, lethality, hospitalization time and costs generated to the health system. Gram-negative bacilli with resistance to multiple antimicrobials, including carbapenems and polymyxins, are currently the most worrying, since the emergence of extensively and even pan-drug-resistant strains is already a reality, especially in hospitals of greater complexity. In Brazil, hyperendemic rates of carbapenem-resistant enterobacteria are reported, mainly due to Klebsiella pneumoniae carbapenemase (KPC)-producing isolates, which are disseminated in several institutions. Conversely, the increasing polymyxin resistance rates in KPC-producing enterobacteria are also reported. One of the recently released alternative against KPC-producing enterobacteria is the new association of antimicrobials ceftazidime-avibactam (CAZ-AVI), with activity on KPC producing isolates. However, CAZ-AVI does not present activity against another subclass of carbapenemase enzymes, the metallo-beta-lactamases (MBL). Among the most frequent MBL variants in enterobacteria in Brazil, the New Delhi Metalobetalactamase (NDM) stands out. NDM was initially described in isolates from Asia but the first case in an invasive clinical isolate of K. pneumoniae was reported in Brazil in 2016, by our group. Since then, NDM-producing K. pneumoniae has been consistently reported in our country, even if still in relatively low proportions. As the Central Public Health Laboratory (LACEN) in the most populous state of the Federation, the Adolfo Lutz Institute receives isolates from several hospitals for characterization and molecular surveillance of antimicrobial resistance. The introduction of a new antimicrobial that does not cover this type of resistance must be carefully monitored, since there are already reports of substitution of KPC for MBL in medical centers that have not used CAZ-AVI in a more rational way. The horizontal transmission of KPC is known to be mediated by Tn4401-like transposon carrier plasmids, however, for NDM this characterization is not well understood. Furthermore, the mechanism of transmission by microvesicles (MVs), which could be independent of the plasmidial machinery, is a new possibility of dispersion, since NDM enzymes have the peculiar ability to anchor to the bacterial plasmatic membrane. In addition to the enzyme, bacterial DNA can also compose the content of MVs. Thus, this study aims to evaluate the behavior of isolates of NDM-producing enterobacteria after the introduction of a new antimicrobial. Through high definition genomic analysis, the core genome and accessory genomes (plasmids) will be sequenced to elucidate transmission mechanisms. We will also study the role of microvesicles as a potential mechanism for the dissemination of genes encoding NDM in these enterobacteria. (AU)

Scientific publications

(4)

(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)

CAMARGO, CARLOS HENRIQUE; YAMADA, AMANDA YAEKO; DE SOUZA, ANDREIA RODRIGUES; CUNHA, MARCOS PAULO VIEIRA; FERRARO, PEDRO SMITH PEREIRA; SACCHI, CLAUDIO TAVARES; DOS SANTOS, MARLON BENEDITO; CAMPOS, KAROLINE RODRIGUES; TIBA-CASAS, MONIQUE RIBEIRO; FREIRE, MARISTELA PINHEIRO; et al. Genomic analysis and antimicrobial activity of β-lactam/β-lactamase inhibitors and other agents against KPC-producing Klebsiella pneumoniae clinical isolates from Brazilian hospitals. SCIENTIFIC REPORTS, v. 13, n. 1, p. 9-pg., 2023-09-05. (18/21192-9, 17/50333-7, 20/06157-2)

CAMARGO, CARLOS HENRIQUE. Current status of NDM-producing Enterobacterales in Brazil: a narrative review. Brazilian Journal of Microbiology, v. N/A, p. 6-pg., 2022-06-11. (17/50333-7, 20/06157-2)

CAMARGO, CARLOS HENRIQUE; YAMADA, AMANDA YAEKO; DE SOUZA, ANDREIA RODRIGUES; REIS, ALEX DOMINGOS; NASCIMENTO SANTOS, MARLON BENEDITO; DE ASSIS, DENISE BRANDAO; DE CARVALHO, ENEAS; TAKAGI, ELIZABETH HARUMMYY; VIEIRA CUNHA, MARCOS PAULO; TIBA-CASAS, MONIQUE RIBEIRO. Genomic Diversity of NDM-Producing Klebsiella Species from Brazil, 2013-2022. ANTIBIOTICS-BASEL, v. 11, n. 10, p. 9-pg., 2022-10-01. (20/06157-2, 17/50333-7)

CAMARGO, CARLOS HENRIQUE; YAMADA, AMANDA YAEKO; NAGAMORI, FILIPE ONISHI; DE SOUZA, ANDREIA RODRIGUES; TIBA-CASAS, MONIQUE RIBEIRO; DE MORAES FRANCA, FLAVIA APARECIDA; TRIGUEIRO NOBREGA PORTO, MARIA HELENA; DE LIMA GARZON, MAGDA LOURDES; HIGGINS, PAUL; MADALOSSO, GERALDINE; et al. Clonal spread of ArmA- and OXA-23-coproducing Acinetobacter baumannii International Clone 2 in Brazil during the first wave of the COVID-19 pandemic. Journal of Medical Microbiology, v. 71, n. 4, p. 6-pg., 2022-01-01. (17/16988-6, 20/06157-2, 17/50333-7, 18/21192-9, 18/21193-5)