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All Publications

  • Antimicrobial activity of cinnamaldehyde against multidrug-resistant Klebsiella pneumoniae: an in vitro and in vivo study. Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] Vaz, M. S., de Almeida de Souza, G. H., Dos Santos Radai, J. A., Fraga, T. L., de Oliveira, G. G., Wender, H., da Silva, K. E., Simionatto, S. 2023


    The emergence and spread of multidrug-resistant (MDR) Klebsiella pneumoniae strains have increased worldwide, posing a significant health threat by limiting the therapeutic options. This study aimed to investigate the antimicrobial potential of cinnamaldehyde against MDR-K. pneumoniae strains in vitro and in vivo assays. The presence of resistant genes in MDR- K. pneumoniae strains were evaluated by Polymerase Chain Reaction (PCR) and DNA sequencing. Carbapenem-resistant K. pneumoniae strains show the blaKPC-2 gene, while polymyxin-resistant K. pneumoniae presented blaKPC-2 and alterations in the mgrB gene. Cinnamaldehyde exhibited an inhibitory effect against all MDR- K. pneumoniae evaluated. An infected mice model was used to determine the in vivo effects against two K. pneumoniae strains, one carbapenem-resistant and another polymyxin-resistant. After 24 h of cinnamaldehyde treatment, the bacterial load in blood and peritoneal fluids decreased. Cinnamaldehyde showed potential effectiveness as an antibacterial agent by inhibiting the growth of MDR-K. pneumoniae strains.

    View details for DOI 10.1007/s42770-023-01040-z

    View details for PubMedID 37392293

    View details for PubMedCentralID 4910107

  • Paratype: a genotyping tool for Salmonella Paratyphi A reveals its global genomic diversity. Nature communications Tanmoy, A. M., Hooda, Y., Sajib, M. S., da Silva, K. E., Iqbal, J., Qamar, F. N., Luby, S. P., Dougan, G., Dyson, Z. A., Baker, S., Garrett, D. O., Andrews, J. R., Saha, S. K., Saha, S. 2022; 13 (1): 7912


    Salmonella Paratyphi A, the primary etiology of paratyphoid, is estimated to cause 3.4 million infections annually, worldwide. With rising antimicrobial resistance and no licensed vaccines, genomic surveillance is key to track and monitor transmission, but there is currently no reliable genotyping framework for this pathogen. Here, we sequence 817 isolates from South Asia and add 562 publicly available genomes to build a global database representing 37 countries, covering 1917-2019. We develop a single nucleotide polymorphism-based genotyping scheme, Paratype, that segregates Salmonella Paratyphi A population into three primary and nine secondary clades, and 18 genotypes. Each genotype is assigned a unique allele definition located on an essential gene. Using Paratype, we identify spatiotemporal genomic variation and antimicrobial resistance markers. We release Paratype as an open-access tool that can use raw read files from both Illumina and Nanopore platforms, and thus can assist surveillance studies tracking Salmonella Paratyphi A across the globe.

    View details for DOI 10.1038/s41467-022-35587-6

    View details for PubMedID 36564386

  • Genetic Diversity of Virulent Polymyxin-Resistant Klebsiella aerogenes Isolated from Intensive Care Units. Antibiotics (Basel, Switzerland) da Silva, K. E., de Almeida de Souza, G. H., Moura, Q., Rossato, L., Limiere, L. C., Vasconcelos, N. G., Simionatto, S. 2022; 11 (8)


    This study evaluated the scope and genetic basis of polymyxin-resistant Klebsiella aerogenes in Brazil. Eight polymyxin-resistant and carbapenemase-producing K. aerogenes strains were isolated from patients admitted to the ICU of a tertiary hospital. Bacterial species were identified by automated systems and antimicrobial susceptibility profile was confirmed using broth microdilution. The strains displayed a multidrug resistant profile and were subjected to whole-genome sequencing. Bioinformatic analysis revealed a variety of antimicrobial resistance genes, including the blaKPC-2. No plasmid-mediated colistin resistance gene was identified. Nonetheless, nonsynonymous mutations in mgrB, pmrA, pmrB, and eptA were detected, justifying the colistin resistance phenotype. Virulence genes encoding yersiniabactin, colibactin, and aerobactin were also found, associated with ICEKp4 and ICEKp10, and might be related to the high mortality observed among the patients. In fact, this is the first time ICEKp is identified in K. aerogenes in Brazil. Phylogenetic analysis grouped the strains into two clonal groups, belonging to ST93 and ST16. In summary, the co-existence of antimicrobial resistance and virulence factors is deeply worrying, as it could lead to the emergence of untreatable invasive infections. All these factors reinforce the need for surveillance programs to monitor the evolution and dissemination of multidrug resistant and virulent strains among critically ill patients.

    View details for DOI 10.3390/antibiotics11081127

    View details for PubMedID 36009996

  • The international and intercontinental spread and expansion of antimicrobial-resistant Salmonella Typhi: a genomic epidemiology study. The Lancet. Microbe da Silva, K. E., Tanmoy, A. M., Pragasam, A. K., Iqbal, J., Sajib, M. S., Mutreja, A., Veeraraghavan, B., Tamrakar, D., Qamar, F. N., Dougan, G., Bogoch, I., Seidman, J. C., Shakya, J., Vaidya, K., Carey, M. E., Shrestha, R., Irfan, S., Baker, S., Luby, S. P., Cao, Y., Dyson, Z. A., Garrett, D. O., John, J., Kang, G., Hooda, Y., Saha, S. K., Saha, S., Andrews, J. R. 2022


    The emergence of increasingly antimicrobial-resistant Salmonella enterica serovar Typhi (S Typhi) threatens to undermine effective treatment and control. Understanding where antimicrobial resistance in S Typhi is emerging and spreading is crucial towards formulating effective control strategies.In this genomic epidemiology study, we sequenced the genomes of 3489 S Typhi strains isolated from prospective enteric fever surveillance studies in Nepal, Bangladesh, Pakistan, and India (between 2014 and 2019), and combined these with a global collection of 4169 S Typhi genome sequences isolated between 1905 and 2018 to investigate the temporal and geographical patterns of emergence and spread of antimicrobial-resistant S Typhi. We performed non-parametric phylodynamic analyses to characterise changes in the effective population size of fluoroquinolone-resistant, extensively drug-resistant (XDR), and azithromycin-resistant S Typhi over time. We inferred timed phylogenies for the major S Typhi sublineages and used ancestral state reconstruction methods to estimate the frequency and timing of international and intercontinental transfers.Our analysis revealed a declining trend of multidrug resistant typhoid in south Asia, except for Pakistan, where XDR S Typhi emerged in 2016 and rapidly replaced less-resistant strains. Mutations in the quinolone-resistance determining region (QRDR) of S Typhi have independently arisen and propagated on at least 94 occasions, nearly all occurring in south Asia. Strains with multiple QRDR mutations, including triple mutants with high-level fluoroquinolone resistance, have been increasing in frequency and displacing strains with fewer mutations. Strains containing acrB mutations, conferring azithromycin resistance, emerged in Bangladesh around 2013 and effective population size of these strains has been steadily increasing. We found evidence of frequent international (n=138) and intercontinental transfers (n=59) of antimicrobial-resistant S Typhi, followed by local expansion and replacement of drug-susceptible clades.Independent acquisition of plasmids and homoplastic mutations conferring antimicrobial resistance have occurred repeatedly in multiple lineages of S Typhi, predominantly arising in south Asia before spreading to other regions.Bill & Melinda Gates Foundation.

    View details for DOI 10.1016/S2666-5247(22)00093-3

    View details for PubMedID 35750070

  • Overview of polymyxin resistance in Enterobacteriaceae REVISTA DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL da Silva, K., Rossato, L., Leite, A., Simionatto, S. 2022; 55: e0349


    Polymyxin antibiotics are disfavored owing to their potential clinical toxicity, especially nephrotoxicity. However, the dry antibiotic development pipeline, together with the increasing global prevalence of infections caused by multidrug-resistant (MDR) gram-negative bacteria, have renewed clinical interest in these polypeptide antibiotics. This review highlights the current information regarding the mechanisms of resistance to polymyxins and their molecular epidemiology. Knowledge of the resistance mechanisms and epidemiology of these pathogens is critical for the development of novel antibacterial agents and rapid treatment choices.

    View details for DOI 10.1590/0037-8682-0349-2021

    View details for Web of Science ID 000766698000017

    View details for PubMedID 35239902

    View details for PubMedCentralID PMC8909443

  • High lethality rate of carbapenem-resistant Acinetobacter baumannii in Intensive Care Units of a Brazilian hospital: An epidemiologic surveillance study REVISTA DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL Lucas Kurihara, M., de Sales, R., da Silva, K., Silva, G., Tazinazzo Mansano, M., Mahmoud, F., Simionatto, S. 2022; 55: e05292021


    Carbapenem-resistant Acinetobacter baumannii (CRAB) is a growing threat to public health.A 3-year retrospective study was conducted to evaluate the prevalence and lethality of multidrug-resistant (MDR) A. baumannii isolated from Brazilian patients.In this study, 219 Acinetobacter baumannii isolates were identified, of which 70.8% (155/219) were isolated from patients hospitalized in intensive care units. Of these, 57.4% (n = 89/155) were assessed, of which 92.1% (82/89) were carbapenem-resistant, and 49 were classified as infected. The lethality rate was 79.6% (39/49).We highlight the need of an effective epidemiological surveillance measure to contain the dissemination of CRAB in the hospital environment.

    View details for DOI 10.1590/0037-8682-0529-2021

    View details for Web of Science ID 000805655300006

    View details for PubMedID 35522809

    View details for PubMedCentralID PMC9070061

  • Local and Travel-Associated Transmission of Tuberculosis at Central Western Border of Brazil, 2014-2017. Emerging infectious diseases Walter, K. S., Tatara, M. B., Esther da Silva, K. n., Moreira, F. M., Dos Santos, P. C., de Melo Ferrari, D. D., Cunha, E. A., Andrews, J. R., Croda, J. n. 2021; 27 (3): 905–14


    International migrants are at heightened risk for tuberculosis (TB) disease. Intensified incarceration at international borders may compound population-wide TB risk. However, few studies have investigated the contributions of migration, local transmission, or prisons in driving incident TB at international borders. We conducted prospective population-based genomic surveillance in 3 cities along Brazil's central western border from 2014-2017. Although most isolates (89/132; 67%) fell within genomic transmission clusters, genetically unique isolates disproportionately occurred among participants with recent international travel (17/42; 40.5%), suggesting that both local transmission and migration contribute to incident TB. Isolates from 40 participants with and 76 without an incarceration history clustered together throughout a maximum-likelihood phylogeny, indicating the close interrelatedness of prison and community epidemics. Our findings highlight the need for ongoing surveillance to control continued introductions of TB and reduce the disproportionate burden of TB in prisons at Brazil's international borders.

    View details for DOI 10.3201/eid2703.203839

    View details for PubMedID 33622493